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EC number: 221-424-4 | CAS number: 3089-17-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
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- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test by Oral Gavage in Sprague Dawley Rats
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 June 2021 to 22 December 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 June 2021 to 22 December 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- As per OECD Guideline for Testing of Chemicals, Number 422, adopted on 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Justification for study design:
- - Basis for dose level selection: There was no information or data available from repeated dose/reproduction toxicity and teratology studies for the test item.
The doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups for the dose range finding study (BIO-DTX 056) in consultation with the sponsor.
There were no test item-related related changes noted in any of the systemic, reproduction and developmental parameters up to the dose level of 1000 mg/kg body weight/day in the Dose Range Finding Study (BIO-DTX 056).
Hence, the same doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively, for the present study in consultation with the sponsor. - Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 21 to 29ºC
- Stability under test conditions: The test item was stable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl cellulose with the concentrations of 5 mg/mL and 100 mg/mL.
- Solubility of the test substance: The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies. - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is one of the standard laboratory rodent species used for toxicity assessment and also recommended by various regulatory authorities.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hylasco Biotechnology India Pvt. Ltd, Charles River Technology Licensee,
CPCSEA (Committee for the Purpose of Control and Supervision of Experiments on Animals) Registration No.: 1808/PO/RcBt/S/15/CPCSEA.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: Males: 254.36 to 291.64 g; Females: 200.54 to 211.92 g
- Housing: Animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
During acclimatization, two animals of same sex were housed.
i. Main Group Animals:
- Pre mating: Per cage two animals of same sex and group were housed.
- Cohabitation Period (mating): Per cage two animals (one male and one female) of same group were housed.
- Post-mating: After confirmation on presence of sperm in the vaginal smear (Day 0 of pregnancy), the mated pairs were separated. Males were housed with their former cage mates while females were housed individually. Sterilized paper shreds were provided as a nesting material for main group females from gestation day 20 onwards.
ii. Recovery Group Animals:
- Maximum of two animals per cage per group of same sex were housed, tunnels were provided as enrichment for the animals which were housed individually.
- Diet (e.g. ad libitum): Altromin maintenance diet
- Water (e.g. ad libitum): Water was provided ad libitum throughout the experimental period. Deep bore-well water passed through reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 to 22.9 oC
- Humidity (%): 48 to 63%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 24 June 2021 To: 16 September 2021 - Route of administration:
- oral: gavage
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 14 days
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy.
- After successful mating each pregnant female was caged (how): After confirmation on presence of sperm in the vaginal smear (Day 0 of pregnancy), the mated pairs were separated. Males were housed with their former cage mates while females were housed individually. Sterilized paper shreds were provided as a nesting material for main group females from gestation day 20 onwards. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and dose formulation analysis for dose concentration verification was performed during week 1 and 5 of the treatment. The results of dose concentration verifications for the prepared test item formulations and the mean results of analysis were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) was less than 15%.
- Duration of treatment / exposure:
- The test item or vehicle were administered to the animals through the oral (gavage) route once daily.
The males were treated for two weeks pre-mating, during mating period and up to the day before sacrifice (total of completion of 31 days of administration).
The females were treated for a two-week pre-mating period (14-days), during mating, pregnancy (gestation) and up to lactation day 13 (ranging from a total period of 50 to 62 days).
The females with positive mating signal, but no-evidence of pregnancy / littering were treated during two-week pre-mating period, during mating and further 24 days from the day of positive mating signal (group G1 - one female until experimental day 39; group G2 - one female until experimental day 52, one female until experimental day 46; G3 - two females until experimental day 49; group G4 - one female until experimental day 39).
The recovery group animals were treated until the first scheduled sacrifice of dams (total of 52 days of administration) and kept without treatment for further 18-days of observation period.
The test item/vehicle was administered by oral (gavage) route using a stainless-steel intubation cannula attached to a disposable syringe. All the doses were administered in an equivolume of 10 mL/kg body weight/day with the concentration of 11.1, 33.3 and 100 mg/mL for low, mid, and high dose groups, respectively. Vehicle was administered to the vehicle control group at an equivolume of 10 mL/kg body weight/day.
The actual dose volume for each animal was calculated based on the most recent body weight. The test item formulations were administered as soon as possible after preparation.
The prepared formulations were stirred using magnetic stirrer during administration to maintain homogeneity. - Frequency of treatment:
- Once Daily
- Details on study schedule:
- - Age at mating of the mated animals in the study: 13 to 14 weeks
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle Control
- Dose / conc.:
- 111 mg/kg bw/day
- Remarks:
- Low Dose
- Dose / conc.:
- 333 mg/kg bw/day
- Remarks:
- Mid Dose
- Dose / conc.:
- 1 000 mg/kg bw/day
- Remarks:
- High Dose
- No. of animals per sex per dose:
- Main Group: 24 (12 Males + 12 Females)
Recovery Group: 10 (5 Males + 5 Females) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: There was no information or data available from repeated dose/reproduction toxicity and teratology studies for the test item.
Based on the above available information, the doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups for the dose range finding study (BIO-DTX 056) in consultation with the sponsor.
There were no test item-related related changes noted in any of the systemic, reproduction and developmental parameters up to the dose level of 1000 mg/kg body weight/day in the Dose Range Finding Study (BIO-DTX 056).
Hence, the same doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively, for the present study in consultation with the sponsor.
- Rationale for animal assignment: The animals were weighed and arranged in ascending order of their body weights. These body weight stratified animals were distributed to all the main and recovery groups using Microsoft Excel Spreadsheet, such that body weight variation of animals selected for the study does not exceed ±20% (Males: -6.80 to 11.14%; Females: -12.58 to 8.29%) of the mean body weight of each sex. The grouping was done one day prior to initiation of treatment. Body weight of the animals were analyzed statistically for mean body weight to rule out statistical significant differences between groups within each sex. - Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily for general clinical signs of toxicity.
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Day 1 before treatment and weekly thereafter during treatment.
BODY WEIGHT: Yes
- Time schedule for examinations: The main group males were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
The main group females were weighed at receipt, on the first day of dosing, weekly thereafter during pre-mating and until confirmation of mating. All the pregnant animals were weighed on gestation days (GD) 0, 7, 14 and 20 and on lactation days (LD) 1, 4, 7, 13 and 14 (terminal body weight). The non-pregnant animals were weighed weekly once until termination and the terminal body weights were recorded before scheduled sacrifice.
The recovery group animals were weighed at receipt, on the first day of dosing, weekly thereafter and at termination. - Oestrous cyclicity (parental animals):
- Oestrus cyclicity was monitored for two weeks after five days of acclimatization to evaluate the normal oestrus cycle (4 to 5 days). Females with normal oestrus cyclicity only were selected for the treatment. Vaginal smears were monitored daily from beginning of the treatment period until evidence of mating. When obtaining vaginal/cervical cells, care was taken to avoid disturbance of mucosa, which may induce pseudopregnancy. The status of oestrus cyclicity of females was determined on termination day.
Recovery group females were not evaluated for oestrus cyclicity - Sperm parameters (parental animals):
- Parameters examined in all males: testis weight, epididymis weight.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in [F1] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, anogenital distance (AGD), presence of nipples/areolae in male pups.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All animals were sacrificed after completion of 31 days of treatment. The males were necropsied in randomized manner.
- Maternal animals: All pregnant females were sacrificed on lactation day 14 and the non-pregnant females were sacrificed after 24 days from the last day of confirmation of mating.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [22] were prepared for microscopic examination and weighed, respectively. - Postmortem examinations (offspring):
- SACRIFICE
- Dead pups and pups which were sacrificed on PND 4/13, examined for gross abnormalities with particular attention to the external reproductive genitals and the findings were recorded.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Statistics:
- The raw data was subjected to computer statistical processing. The computer printout of the data (in the form of an appendix) was verified with the raw data. After verification, the data was subjected to various statistical analyses using SPSS software version 22.
All analysis and comparisons were evaluated at 95% with the level of confidence of P<0.05 respectively, indicated by the aforementioned tests and were designated by the superscripts throughout the report as stated below:
* Statistically significant (P<0.05) change than the vehicle control group.
Note: Data of non-pregnant females was excluded for mean calculations and statistical analysis for reproductive end points but considered for systemic parameters. However, the individual animal data is presented in appendices.
The statistical analysis tests followed for the interpretation of data are as mentioned below:
Parametric - One-way ANOVA
• Body weight (weekly/gestation/lactation)
• Percent Change in body weight (weekly/gestation/lactation)
• Feed consumption (weekly/gestation/lactation)
• Copulatory interval
• Gestation length
• Hematology
• Clinical chemistry
• Urinalysis
• Absolute/relative organ weights
• Functional Observation parameters
• Mean pup weight per litter
• Mean pup anogenital distance ratio per litter
• Serum T4 values (adults/pups).
Non Parametric - Kruskal-Wallis
• Implantations/litter
• No. of pups/litter
• Sex ratio/litter
• Litter size
• No. of early resorptions/litter
• No. of late resorptions/litter
• Prenatal loss/litter
• Postnatal loss/litter
Cross Tabs - Chi-square test
• Reproductive performances (frequency occurrences)
- mated/non-mated;
- fertile/infertile;
- pregnant/non-pregnant;
- with/without live pups;
- with/without dead pups - Reproductive indices:
- The following reproductive performance indices were calculated as mentioned below and presented in the study report,
Male Mating Index (%) = No. of males with confirmed mating / Total No. of males cohabited x 100
Female Mating Index (%) = No. of sperm-positive females / Total No. of females cohabited x 100
Male Fertility Index (%) = No. of males impregnating a female / Total No. of males mated x 100
Female Fertility Index (%) = No. of pregnant females / No. of sperm-positive females x 100
Pre-coital Interval (Days) = Date of confirmation of mating – Date of initiation of cohabitation
Gestation Length (days) = Date of parturition – Date of positive evidence of mating (GD 0)
Gestation Index (%) = No. of females with live born / No. of females with evidence of pregnancy x 100
Parturition Index (%) = No. of females littered / No. of females with evidence of pregnancy x 100
Pregnancy Index (%) = No. of pregnant females / No. of females with confirmed mating x 100 - Offspring viability indices:
- Sex ratio (m/f) = No. of male offspring / Number of female offspring
Live Birth Index (%) per litter = No. of pups born alive / Total No. of pups born x 100
Pup Survival index (%) on LD 4/7/13 = Total No. of live pups on LD 4/7/13 / No. of pups born/4/7/13 x 100
Sex ratio (m/f) on LD 4/7/13 = No. of male offspring on LD 4/7/13 / No. of female offspring on LD 4/7/13
Post-Implantation Loss (%) = No. of implantations - No. of viable pups / No. of implantations x 100
Post-implantation Loss (No.) = No. of implantations - No. of live births
Postnatal loss on LD 13 (%) = No. of pups alive on postnatal day 13 /No. of live pups at birth x 100
Postnatal Loss on LD 13 (No.) = Live births - pups alive at lactation day 13
Anogenital Distance (AGD) Ratio = Anogenital distance (mm) / Cube root of PND 4 pup weight x 100 - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- ca. 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food efficiency
- ophthalmological examination
- haematology
- clinical biochemistry
- urinalysis
- organ weights and organ / body weight ratios
- gross pathology
- histopathology: non-neoplastic
- reproductive function (oestrous cycle)
- reproductive function (sperm measures)
- reproductive performance
- other: Thyroid hormonal levels
- Key result
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Gross pathological findings:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no changes in mean serum T4 hormone levels of pups at postnatal day 13 in any of the tested dose group litters when compared with vehicle control group litters. However, an incidental statistically significant decrease in mean T4 levels in pups was noted in groups G2, G3 and G4 when compared with vehicle control group.
- Description (incidence and severity):
- The oral administration of test item Hostaperm Red Violet ER 02 over the time of the study, did not produce any indication of developmental toxicity at the dose levels of 111, 333 and 1000 mg/kg body weight/day.
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- ca. 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- other: Serum Thyroid hormonal levels (T4)
- Key result
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- The oral administration of test item over the time of the study, carried out according to the OECD guideline 422 (for main group males with a total of 31 days, for main group females ranging from 50 to 62 days and for recovery group animals with a total period of 52 days) did not produce any indication of systemic, reproduction and developmental toxicity at the dose levels of 111, 333 and 1000 mg/kg body weight/day under experimental conditions employed.
Therefore, the no-observed-adverse-effect-level (NOAEL) of test item is considered as 1000 mg/kg body weight for systemic, reproduction and developmental toxicity end points. - Executive summary:
The objective of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test by oral gavage in Sprague Dawley Rats was to determine the possible health hazards likely to arise from repeated exposure to the test item over a relatively limited period of time. This study was also conducted to provide initial information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition and an estimate of the No Observed Adverse Effect Level (NOAEL).
A total of 116 (58 males + 58 females) Sprague Dawley rats were selected for the study and distributed to four main (G1, G2, G3 and G4) and two recovery groups (G1R and G4R). Each main group consisted of 12 males and 12 females and each recovery group consisted of 5 males and 5 females. The animals in group G1/G1R were administered with vehicle [0.5% w/v Carboxymethyl Cellulose], animals in groups G2, G3 and G4/G4R were administered with test item at the dose levels of 111, 333 and 1000 mg/kg body weight/day for low, mid and high/high dose recovery, respectively. Vehicle and test item formulations were administered orally by gavage with the dose volume of 10 mL/kg body weight/day once daily at similar times on each day for 7 days a week.
All the main group males were administered with test item during pre-mating (14 -days), during mating and during post-mating period (total of 31 days). The pregnant females from main groups were administered with test item during pre-mating (14 -days), during mating, pregnancy (gestation) and up to lactation day 13. The females with positive mating signal, but no-evidence of pregnancy / littering were administered with test item during pre-mating (14 -days), during mating, and further 24 days from the day of positive mating signal. All the recovery group animals were administered with test item for 50 days followed by a 14 -day observation period without treatment.
The test item formulations were stable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl Cellulose with the concentrations of 5 mg/mL and 100 mg/mL. The homogeneity and dose form concentration analysis for prepared test item formulations during treatment period was performed during week 1 and 5 and the mean results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%.
For systemic toxicity assessment, all the animals (main and recovery groups) of both sexes were observed once daily for clinical signs, twice daily for mortality and morbidity and once in a week for detailed clinical examination. Body weight of all the animals (main and recovery groups) of both sexes were recorded once in a week until termination. Further, the body weight of all pregnant females was recorded on gestation day (GD) 0, 7, 14 and 20 during pregnancy and on lactation day (LD) 1, 4, 7, 13 and 14 during lactation. Body weight of all non-pregnant females was recorded once in a week until termination. Feed consumption for all the animals of both sexes were recorded once in a week during pre-mating for main groups and throughout the experimental period for recovery groups. Further, feed consumption of all pregnant females was recorded during GD 0 to 7, 7 to 14 and 14 to 20 and during LD 1 to 4, 4 to 7 and 7 to 13. Ophthalmological examination was carried out once before treatment and at the end of the dosing period for all males and females (main and recovery groups).
Neurological/functional observations were performed for five randomly selected males and females from each main group, for all animals from recovery groups towards end of the dosing period. The investigations of haematology and clinical chemistry for all animals (main and recovery groups), investigations of urinalysis for five randomly selected males from each main group and for all recovery groups animals was conducted at termination. Serum thyroxine hormone (T4) levels were estimated for all main group males by ELISA. The organs were collected and weighed on the day of termination for all animals (main and recovery groups) of both sexes and organ weight relative to terminal body weight was calculated. All the animals (main and recovery groups) of both sexes were observed for both external and internal gross pathological changes during conduct of necropsy. Histopathological examination was conducted on all the tissues collected from the groups G1 and G4 animals with special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure.
For reproductive toxicity assessment, all the males (main groups) were evaluated for reproductive performances such as, mating and fertility indices. All the females (main groups) were evaluated for reproductive performances such as, mating, fertility, gestation and parturition indices. The females were also evaluated for pre-coital interval and gestation length. All females were evaluated for oestrus cyclicity during pre-mating period and the vaginal smear examination was continued until evidence of mating. At birth (delivery) parameters such as, number of live/dead pups born, litter size, sex ratio (m/f) and live birth index per litter were observed / calculated. The litter observations during lactation period such as, number of survived or dead pups, sex ratio (m/f) and pup survival index per litter were observed / calculated. The total number of implantation sites was recorded for each litter during necropsy and the post-implantation and postnatal losses per litter was calculated.
For developmental toxicity assessment, all survived pups from each litter were observed once daily for external behavioural changes and twice daily for mortality until termination [postnatal day (PND) 13]. All pups from each litter were weighed individually on PND 1, 4, 7 and 13 and measured for anogenital distance on PND 4. All male pups were observed for retention of nipples on PND 13. All the pups were subjected for both external and internal gross pathological changes during conduct of necropsy. The collected serum from PND 13 pups was subjected to estimation of thyroxine hormone (T4) levels using ELISA.
There were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals from all the tested dose groups, however dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4R animals. This coloration is due to colored nature of the test item but not any adverse sign. Detailed clinical examination did not reveal any changes in any of the tested dose group animals. No changes noted in mean body weight, percent change in mean body weight gain and mean feed consumption in all the tested dose groups of both sexes. The ophthalmological examination and neurological/functional examinations did not reveal any test item-related changes in any of the animals from all the tested dose groups of both sexes. The obtained mean haematology, clinical chemistry and urinalysis values did not reveal any test item-related changes in all the tested dose groups. The estimated serum T4 levels did not reveal any changes. The absolute and relative organ weights of both sexes did not reveal any changes from all the tested dose groups.
No treatment related gross pathological changes were noted in any of the animals from all the tested dose groups during necropsy, however in test item administered animals of both sexes, the contents of gastrointestinal tract were found to be violet in color which was attributed to the color of the test item and was considered as non-adverse effect as the mucosa of gastrointestinal tract was found to be within normal limits.
No treatment related microscopic findings noted in any of the tissues/organs subjected for histopathological evaluation from both high dose group and vehicle control group animals of both sexes.
There were no effects noted on reproductive performance of both sexes in all the tested dose groups. No test item-related irregularities observed in oestrus cyclicity of the females from all the tested dose groups during treatment period. No changes were noted in ‘at birth’ (delivery) and or ‘litter observations’ in all the tested dose groups. No effects were noted for live birth index and pup survival index in all the tested dose groups. No test item-related post-implantation losses were noted in all the tested dose groups.
There were no developmental/external behavioural changes noted and no test item-related mortalities noted during postnatal period in any of pups from all the tested dose group litters. The mean pup weight, mean anogenital distance and its ratio in either sex of pups per litter were un-affected by the test item in all the tested dose groups. There were no incidences of retention of nipples in male pups examined on PND 13 from all the tested dose and control group litters. The estimated serum T4 levels of PND 13 (from all litters) pups did not reveal any changes in all the tested dose group litters. There were no gross pathological changes noted in any of the pups during scheduled sacrifice from all the tested dose and control group litters.
TABLE 1. SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, M & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, M & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, M & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, M & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
M:
Male; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, F & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, F & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, F & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, F & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
F:
Female; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1R, M & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, M & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
G1R, F & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, F & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
M :
Male; F: Female; R: Recovery; N: Normal; NAD: No abnormality detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark
purple colored faeces were noted from day 2 throughout the experiment
period till termination in group G4R animals.
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
|||||
1 |
7 |
14 |
21 |
28 |
|||
G1, M & 0 |
Mean |
400.75 |
421.20 |
438.19 |
446.01 |
458.77 |
|
±SD |
22.07 |
32.34 |
36.49 |
37.08 |
38.53 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
401.74 |
417.26 |
433.41 |
442.75 |
452.56 |
|
±SD |
20.39 |
24.35 |
30.70 |
31.29 |
30.16 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
402.72 |
419.51 |
438.54 |
444.84 |
456.36 |
|
±SD |
19.35 |
23.54 |
30.11 |
27.23 |
24.95 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
401.99 |
422.76 |
443.74 |
453.94 |
463.38 |
|
±SD |
21.50 |
27.21 |
34.32 |
36.83 |
39.17 |
||
n |
12 |
12 |
12 |
12 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||
1 |
7 |
14 |
21# |
|||
G1, F & 0 |
Mean |
250.88 |
257.35 |
267.91 |
280.34 |
|
±SD |
14.86 |
17.17 |
18.25 |
26.26 |
||
n |
12 |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
251.05 |
256.43 |
266.53 |
272.56 |
|
±SD |
12.78 |
15.62 |
15.30 |
25.98 |
||
n |
12 |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
251.13 |
256.32 |
261.08 |
260.46 |
|
±SD |
13.59 |
14.00 |
15.94 |
17.45 |
||
n |
12 |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
251.24 |
261.46 |
265.51 |
269.05 |
|
±SD |
15.56 |
18.91 |
20.71 |
24.37 |
||
n |
12 |
12 |
12 |
4 |
F: Female; SD: Standard Deviation; n: Number of Animals.
#: The data obtained from females in cohabitation only considered for mean calculations.
The data of day 21 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||||||||
1 |
7 |
14 |
21 |
28 |
35 |
42 |
49 |
56 |
63 |
|||
G1R, M & 0 |
Mean |
395.45 |
407.17 |
422.63 |
436.11 |
448.75 |
458.35 |
473.23 |
489.33 |
502.87 |
514.37 |
|
±SD |
21.72 |
21.10 |
31.29 |
32.45 |
32.78 |
34.62 |
33.67 |
33.58 |
34.92 |
37.99 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
396.36 |
412.35 |
430.15 |
444.31 |
454.98 |
464.82 |
475.04 |
493.68 |
508.20 |
519.69 |
|
±SD |
20.86 |
20.17 |
12.53 |
16.96 |
17.27 |
14.72 |
15.50 |
9.28 |
11.65 |
11.69 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
245.24 |
250.97 |
262.44 |
268.72 |
277.56 |
284.92 |
295.96 |
306.72 |
315.86 |
324.75 |
|
±SD |
10.97 |
10.11 |
13.68 |
15.80 |
15.60 |
15.72 |
19.40 |
19.59 |
17.41 |
15.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
245.66 |
248.99 |
264.41 |
270.43 |
278.43 |
286.33 |
298.35 |
308.32 |
318.51 |
327.87 |
|
±SD |
12.82 |
12.43 |
13.84 |
12.16 |
11.19 |
12.10 |
12.79 |
13.72 |
10.97 |
12.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 3. SUMMARY RECORD OF GESTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Gestation Day (GD) |
||||
0 |
7 |
14 |
20 |
||
G1, F & 0 |
Mean |
272.42 |
287.38 |
319.92 |
375.62 |
±SD |
18.33 |
21.41 |
28.89 |
35.87 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
269.81 |
286.87 |
328.45 |
391.71 |
±SD |
11.98 |
12.37 |
15.11 |
22.46 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
264.91 |
282.42 |
317.51 |
369.85 |
±SD |
15.69 |
14.58 |
20.68 |
32.90 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
273.49 |
291.35 |
327.07 |
382.89 |
±SD |
17.37 |
17.37 |
23.26 |
39.30 |
|
n |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis, but presented in individual animal data.
TABLE 4. SUMMARY RECORD OF LACTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Lactation Day (LD) |
||||
1 |
4 |
7 |
13 |
||
G1, F & 0 |
Mean |
294.60 |
300.48 |
308.18 |
323.25 |
±SD |
22.07 |
22.28 |
22.06 |
20.39 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
306.24 |
309.48 |
314.78 |
330.57 |
±SD |
22.46 |
21.39 |
20.72 |
19.26 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
293.35 |
297.31 |
304.48 |
319.65 |
±SD |
19.47 |
20.23 |
20.46 |
22.22 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
303.31 |
306.82 |
313.01 |
325.64 |
±SD |
22.77 |
24.10 |
23.73 |
23.27 |
|
n |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 5. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
||||
1 to 7 |
1 to 14 |
1 to 21 |
1 to 28 |
|||
G1, M & 0 |
Mean |
5.01 |
9.25 |
11.19 |
14.36 |
|
±SD |
3.10 |
4.96 |
4.86 |
4.98 |
||
n |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
3.84 |
7.80 |
10.13 |
12.59 |
|
±SD |
2.04 |
3.09 |
3.48 |
3.20 |
||
n |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
4.15 |
8.89 |
10.50 |
13.42 |
|
±SD |
2.15 |
5.14 |
5.14 |
5.61 |
||
n |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
5.12 |
10.29 |
12.82 |
15.16 |
|
±SD |
1.91 |
3.83 |
4.55 |
5.27 |
||
n |
12 |
12 |
12 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 5 (Contd…). SUMMARY OF PERCENTCHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||
1 to 7 |
1 to 14 |
1 to 21# |
|||
G1, F & 0 |
Mean |
2.56 |
6.78 |
10.07 |
|
±SD |
2.21 |
3.23 |
3.01 |
||
n |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
2.12 |
6.21 |
9.94 |
|
±SD |
2.46 |
4.16 |
1.49 |
||
n |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
2.08 |
3.94 |
5.98 |
|
±SD |
1.81 |
2.08 |
1.64 |
||
n |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
4.05 |
5.61 |
9.37 |
|
±SD |
3.24 |
3.20 |
3.75 |
||
n |
12 |
12 |
4 |
F: Female; SD: Standard Deviation; n: Number of Animals.
#: The data obtained from females in cohabitation only considered for mean calculations. The data of day 1 to 21 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 5 (Contd…). SUMMARY OF PERCENTCHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||||||||
1 to 7 |
1 to 14 |
1 to 21 |
1 to 28 |
1 to 35 |
1 to 42 |
1 to 49 |
1 to 56 |
1 to 63 |
|||
G1R, M & 0 |
Mean |
2.98 |
6.83 |
10.25 |
13.47 |
15.92 |
19.69 |
23.73 |
27.13 |
30.00 |
|
±SD |
0.92 |
4.09 |
4.67 |
5.29 |
6.27 |
5.81 |
4.88 |
4.25 |
4.30 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
4.06 |
8.66 |
12.20 |
14.91 |
17.44 |
20.09 |
24.77 |
28.45 |
31.32 |
|
±SD |
1.73 |
3.60 |
3.33 |
3.84 |
4.90 |
6.78 |
5.51 |
6.10 |
5.14 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
2.35 |
7.00 |
9.55 |
13.20 |
16.19 |
20.62 |
25.02 |
28.77 |
32.44 |
|
±SD |
0.72 |
2.36 |
3.15 |
4.61 |
4.45 |
4.14 |
4.54 |
3.55 |
3.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.37 |
7.66 |
10.20 |
13.45 |
16.65 |
21.52 |
25.60 |
29.78 |
33.57 |
|
±SD |
1.07 |
2.71 |
4.80 |
4.07 |
3.73 |
3.02 |
4.10 |
3.75 |
3.31 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 6. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Gestation Day (GD) |
|||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
5.46 |
11.22 |
17.44 |
±SD |
1.77 |
2.82 |
4.18 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
6.35 |
14.52 |
19.23 |
±SD |
2.12 |
3.20 |
3.16 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
6.67 |
12.40 |
16.35 |
±SD |
1.92 |
3.55 |
3.43 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
6.56 |
12.23 |
16.88 |
±SD |
1.60 |
3.35 |
4.81 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis, but presented in individual animal data.
TABLE 7. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Lactation Day (LD) |
|||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
2.01 |
2.58 |
4.96 |
±SD |
0.96 |
0.73 |
1.51 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
1.08 |
1.74 |
5.07 |
±SD |
0.86 |
0.95 |
1.60 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
1.35 |
2.42 |
4.98 |
±SD |
0.95 |
1.29 |
1.32 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
1.14 |
2.04 |
4.06 |
±SD |
1.00 |
0.93 |
0.83 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 8. SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/animal/day) during Pre-mating Period |
||
Week 1 |
Week 2 |
||
G1, M & 0 |
Mean |
21.31 |
24.01 |
±SD |
2.38 |
1.81 |
|
n |
12 (6) |
12 (6) |
|
G2, M & 111 |
Mean |
21.39 |
23.12 |
±SD |
1.76 |
0.75 |
|
n |
12 (6) |
12 (6) |
|
G3, M & 333 |
Mean |
22.25 |
23.93 |
±SD |
2.39 |
1.85 |
|
n |
12 (6) |
12 (6) |
|
G4, M & 1000 |
Mean |
22.28 |
24.17 |
±SD |
1.23 |
0.67 |
|
n |
12 (6) |
12 (6) |
M: Male; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/animal/day) during Pre-mating Period |
||
Week 1 |
Week 2 |
||
G1, F & 0 |
Mean |
18.14 |
19.17 |
±SD |
1.56 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
G2, F & 111 |
Mean |
17.79 |
20.11 |
±SD |
1.85 |
1.70 |
|
n |
12 (6) |
12 (6) |
|
G3, F & 333 |
Mean |
18.26 |
19.22 |
±SD |
1.99 |
1.31 |
|
n |
12 (6) |
12 (6) |
|
G4, F & 1000 |
Mean |
18.43 |
20.07 |
±SD |
2.28 |
1.22 |
|
n |
12 (6) |
12 (6) |
F: Female; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) |
||||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
Week 7 |
Week 8 |
Week 9 |
||
G1R, M & 0 |
Mean |
23.52 |
24.34 |
25.11 |
26.35 |
27.86 |
29.05 |
30.75 |
31.83 |
32.47 |
±SD |
3.71 |
1.67 |
1.55 |
1.27 |
0.97 |
1.11 |
0.47 |
3.66 |
3.01 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, M & 1000 |
Mean |
22.84 |
23.75 |
24.26 |
27.17 |
28.86 |
30.05 |
31.07 |
32.19 |
33.03 |
±SD |
0.77 |
1.04 |
1.34 |
2.09 |
2.61 |
2.18 |
2.12 |
1.59 |
1.67 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G1R, F & 0 |
Mean |
17.44 |
18.36 |
19.45 |
10.21 |
23.17 |
24.20 |
25.35 |
26.19 |
27.04 |
±SD |
1.79 |
0.40 |
0.40 |
9.72 |
0.99 |
0.82 |
0.62 |
0.41 |
0.99 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, F & 1000 |
Mean |
17.21 |
19.05 |
20.42 |
11.29 |
24.18 |
25.37 |
26.19 |
27.14 |
27.89 |
±SD |
0.69 |
1.77 |
0.91 |
10.38 |
0.03 |
0.80 |
0.84 |
0.69 |
0.68 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals(Number of cages).
TABLE 9. SUMMARY RECORD OF FEED CONSUMPTION (g/animal/day) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) during Gestation Day (GD) |
||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
19.02 |
21.07 |
25.81 |
SD |
0.70 |
1.95 |
1.63 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
19.23 |
22.20 |
26.84 |
SD |
0.88 |
1.81 |
1.78 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
19.00 |
21.49 |
26.11 |
SD |
0.74 |
1.39 |
1.26 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
19.43 |
22.01 |
26.67 |
SD |
0.58 |
1.70 |
1.97 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis but presented in individual animal data.
TABLE 10. SUMMARY RECORD OF FEED CONSUMTION (g/animal/day) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) during Lactation Day (LD) |
||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
25.21 |
35.80 |
40.88 |
SD |
1.20 |
7.26 |
1.43 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
24.58 |
32.72 |
41.09 |
SD |
1.34 |
0.99 |
0.98 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
25.11 |
32.75 |
40.54 |
SD |
1.42 |
1.16 |
0.94 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
23.94 |
33.14 |
39.84 |
SD |
5.99 |
1.28 |
1.03 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 11. SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 30 |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Pregnant/Littered females: Lactation day 13; Non-pregnant females: (Experimental day 39 to 52) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 12. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.4 |
4.8 |
4.8 |
4.8 |
|
±SD |
1.1 |
0.8 |
0.8 |
0.8 |
||
Number of urine pools |
Mean |
3.4 |
3.8 |
3.8 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.8 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.1 |
98.4 |
|
±SD |
0.5 |
0.4 |
0.3 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.8 |
4.8 |
4.8 |
4.8 |
|
±SD |
0.8 |
0.8 |
0.8 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
2.8 |
3.2 |
|
±SD |
0.9 |
0.7 |
0.8 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
2.6 |
3.0 |
|
±SD |
0.4 |
0.8 |
0.5 |
0.7 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.8 |
98.7 |
|
±SD |
0.6 |
0.5 |
0.5 |
0.8 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.4 |
|
±SD |
1.0 |
1.1 |
||
Numbers of urine pools |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Number of defecations |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.6 |
3.2 |
|
±SD |
0.5 |
0.4 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.5 |
98.6 |
|
±SD |
0.5 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.8 |
|
±SD |
1.0 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
|
±SD |
0.9 |
0.7 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
|
±SD |
0.4 |
0.8 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.4 |
98.3 |
|
±SD |
0.5 |
0.7 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 13. SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
1911.4 |
±SD |
108.9 |
|
n |
5 |
|
G2, M & 111 |
Mean |
1961.8 |
±SD |
138.9 |
|
n |
5 |
|
G3, M & 333 |
Mean |
1954.2 |
±SD |
126.1 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
1931.4 |
±SD |
104.0 |
|
n |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, F & 0 |
Mean |
1923.4 |
±SD |
102.7 |
|
n |
5 |
|
G2, F & 111 |
Mean |
1941.4 |
±SD |
125.1 |
|
n |
5 |
|
G3, F & 333 |
Mean |
1989.0 |
±SD |
103.1 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
1973.2 |
±SD |
84.7 |
|
n |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1R, M & 0 |
Mean |
2014.2 |
±SD |
210.7 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
1980.6 |
±SD |
197.8 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
1943.4 |
±SD |
87.8 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
1956.2 |
±SD |
91.6 |
|
n |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 14. SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 30 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, M & 0 |
Mean |
1.529 |
0.510 |
±SD |
0.023 |
0.025 |
|
n |
5 |
5 |
|
G2, M & 111 |
Mean |
1.501 |
0.539 |
±SD |
0.020 |
0.021 |
|
n |
5 |
5 |
|
G3, M & 333 |
Mean |
1.521 |
0.552* |
±SD |
0.048 |
0.008 |
|
n |
5 |
5 |
|
G4, M & 1000 |
Mean |
1.539 |
0.544* |
±SD |
0.040 |
0.015 |
|
n |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Lactation Day 13 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, F & 0 |
Mean |
1.496 |
0.508 |
±SD |
0.009 |
0.008 |
|
n |
5 |
5 |
|
G2, F & 111 |
Mean |
1.493 |
0.488 |
±SD |
0.010 |
0.015 |
|
n |
5 |
5 |
|
G3, F & 333 |
Mean |
1.496 |
0.493 |
±SD |
0.009 |
0.021 |
|
n |
5 |
5 |
|
G4, F & 1000 |
Mean |
1.498 |
0.499 |
±SD |
0.011 |
0.020 |
|
n |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 65 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1R, M & 0 |
Mean |
1.515 |
0.534 |
±SD |
0.020 |
0.035 |
|
n |
5 |
5 |
|
G4R, M & 1000 |
Mean |
1.528 |
0.533 |
±SD |
0.029 |
0.009 |
|
n |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.516 |
0.499 |
±SD |
0.031 |
0.021 |
|
n |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.503 |
0.481 |
±SD |
0.012 |
0.012 |
|
n |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 15. SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, M & 0 |
Mean |
9.0 |
±SD |
1.0 |
|
n |
5 |
|
G2, M & 111 |
Mean |
8.8 |
±SD |
1.3 |
|
n |
5 |
|
G3, M & 333 |
Mean |
9.3 |
±SD |
0.6 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
8.6 |
±SD |
0.6 |
|
n |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, F & 0 |
Mean |
8.0 |
±SD |
0.5 |
|
n |
5 |
|
G2, F & 111 |
Mean |
7.9 |
±SD |
0.5 |
|
n |
5 |
|
G3, F & 333 |
Mean |
8.1 |
±SD |
1.0 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
8.5 |
±SD |
0.9 |
|
n |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1R, M & 0 |
Mean |
8.6 |
±SD |
0.3 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
9.0 |
±SD |
0.4 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
8.4 |
±SD |
0.4 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
7.6* |
±SD |
0.2 |
|
n |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, M & 0 |
Mean |
8.26 |
9.64 |
17.56 |
52.80 |
55.00 |
18.30 |
33.26 |
776.40 |
7.72 |
±SD |
1.95 |
1.09 |
1.34 |
4.49 |
3.09 |
1.14 |
0.53 |
330.86 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
9.68 |
9.37 |
16.82 |
51.32 |
54.72 |
17.94 |
32.80 |
1135.20 |
7.46 |
±SD |
2.59 |
0.15 |
0.33 |
0.89 |
1.12 |
0.29 |
0.58 |
184.30 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
8.67 |
9.40 |
16.58 |
50.78 |
54.12 |
17.64 |
32.62 |
962.60 |
7.72 |
±SD |
3.67 |
0.62 |
0.87 |
1.91 |
1.72 |
0.59 |
0.70 |
256.00 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
8.14 |
9.35 |
16.88 |
52.02 |
55.74 |
18.06 |
32.46 |
1017.60 |
7.50 |
±SD |
2.42 |
0.54 |
0.55 |
1.58 |
2.71 |
0.74 |
0.53 |
93.02 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, M & 0 |
Mean |
2.25 |
23.48 |
72.02 |
2.38 |
0.44 |
0.80 |
±SD |
1.24 |
9.09 |
9.80 |
1.15 |
0.17 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
1.87 |
19.66 |
75.74 |
2.28 |
1.04 |
0.54 |
±SD |
0.64 |
3.44 |
3.55 |
0.74 |
0.59 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
1.87 |
21.98 |
70.58 |
2.40 |
1.04 |
0.62 |
±SD |
0.60 |
5.35 |
7.57 |
2.37 |
0.34 |
0.61 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
2.01 |
20.86 |
75.78 |
1.42 |
0.72 |
0.54 |
±SD |
0.79 |
3.34 |
2.92 |
0.23 |
0.25 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, M & 0 |
Mean |
212.96 |
1.83 |
6.07 |
0.19 |
0.04 |
0.07 |
15.54 |
22.26 |
±SD |
101.87 |
0.42 |
2.01 |
0.08 |
0.02 |
0.06 |
0.78 |
6.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
174.50 |
1.91 |
7.33 |
0.23 |
0.10* |
0.05 |
15.72 |
25.28 |
±SD |
56.93 |
0.64 |
1.96 |
0.10 |
0.04 |
0.02 |
1.03 |
1.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
175.20 |
1.80 |
5.98 |
0.27 |
0.09* |
0.07 |
16.72 |
24.30 |
±SD |
59.25 |
0.52 |
1.97 |
0.39 |
0.03 |
0.11 |
1.49 |
1.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
184.78 |
1.70 |
6.17 |
0.11 |
0.06 |
0.04 |
15.98 |
26.78 |
±SD |
67.09 |
0.55 |
1.89 |
0.04 |
0.02 |
0.02 |
0.89 |
1.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, F & 0 |
Mean |
10.56 |
7.85 |
15.74 |
46.26 |
59.02 |
20.04 |
34.04 |
752.60 |
6.02 |
±SD |
3.78 |
0.45 |
0.65 |
3.16 |
4.16 |
1.08 |
0.91 |
361.58 |
0.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
11.38 |
7.41 |
14.66 |
44.60 |
60.26 |
19.74 |
32.82 |
1130.00 |
6.72 |
±SD |
3.45 |
0.68 |
1.58 |
3.35 |
1.37 |
0.42 |
1.34 |
672.21 |
0.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
9.62 |
7.95 |
15.56 |
46.34 |
58.34 |
19.60 |
33.60 |
1030.20 |
6.42 |
±SD |
3.95 |
0.28 |
0.72 |
2.05 |
3.12 |
0.81 |
1.07 |
104.22 |
0.57 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
12.38 |
7.39 |
14.68 |
43.46 |
59.06 |
19.98 |
33.80 |
1003.00 |
6.92 |
±SD |
3.58 |
0.76 |
0.89 |
2.75 |
3.76 |
1.58 |
0.63 |
227.17 |
0.68 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, F & 0 |
Mean |
2.28 |
32.72 |
60.66 |
3.68 |
1.46 |
0.60 |
±SD |
0.87 |
15.77 |
16.88 |
1.06 |
0.98 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
4.52 |
30.00 |
62.56 |
4.60 |
1.18 |
0.42 |
±SD |
4.56 |
11.00 |
11.24 |
1.35 |
0.63 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
1.49 |
25.26 |
66.92 |
4.46 |
1.22 |
0.80 |
±SD |
0.67 |
9.73 |
12.89 |
4.23 |
0.33 |
1.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.16 |
37.00 |
57.76 |
3.10 |
0.88 |
0.28 |
±SD |
2.72 |
20.56 |
20.80 |
0.97 |
0.47 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, F & 0 |
Mean |
177.36 |
3.64 |
6.21 |
0.40 |
0.15 |
0.06 |
17.60 |
23.34 |
±SD |
60.94 |
2.11 |
2.30 |
0.19 |
0.09 |
0.03 |
1.02 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
313.86 |
3.59 |
6.91 |
0.56 |
0.12 |
0.05 |
22.06 |
27.48 |
±SD |
276.22 |
2.17 |
1.72 |
0.29 |
0.04 |
0.02 |
8.41 |
10.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
117.60 |
2.64 |
6.29 |
0.39 |
0.12 |
0.06 |
16.88 |
22.08 |
±SD |
50.69 |
2.06 |
2.26 |
0.31 |
0.07 |
0.08 |
3.84 |
7.81 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
291.70 |
4.81 |
6.94 |
0.38 |
0.10 |
0.04 |
15.66 |
19.92 |
±SD |
145.98 |
3.66 |
3.06 |
0.17 |
0.03 |
0.02 |
3.85 |
5.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1R, M & 0 |
Mean |
9.13 |
9.21 |
16.04 |
48.76 |
52.94 |
17.42 |
32.92 |
894.80 |
6.50 |
±SD |
0.78 |
0.14 |
0.43 |
1.79 |
1.78 |
0.39 |
0.42 |
134.10 |
0.31 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
9.55 |
9.14 |
15.80 |
48.54 |
53.08 |
17.30 |
32.62 |
1071.80 |
6.42 |
±SD |
1.05 |
0.32 |
0.65 |
2.25 |
0.91 |
0.30 |
0.57 |
268.87 |
0.37 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
6.97 |
7.65 |
14.26 |
42.16 |
55.20 |
18.64 |
33.78 |
873.60 |
6.32 |
±SD |
2.14 |
0.43 |
0.65 |
2.05 |
1.99 |
0.70 |
0.29 |
80.79 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
7.59 |
7.73 |
14.32 |
42.78 |
55.34 |
18.48 |
33.46 |
739.60 |
6.52 |
±SD |
3.51 |
0.22 |
0.57 |
1.63 |
2.15 |
0.70 |
0.25 |
253.21 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1R, M & 0 |
Mean |
1.63 |
25.28 |
69.00 |
1.76 |
2.30 |
0.88 |
±SD |
0.26 |
6.62 |
7.82 |
0.49 |
0.89 |
0.26 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
2.03 |
21.70 |
73.32 |
1.48 |
2.02 |
0.60 |
±SD |
0.50 |
5.52 |
5.80 |
0.37 |
0.36 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
26.12 |
68.68 |
2.30 |
1.34 |
0.68 |
±SD |
0.36 |
9.06 |
8.57 |
1.19 |
0.45 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
2.48* |
29.02 |
64.16 |
2.40 |
2.86* |
0.64 |
±SD |
0.39 |
7.89 |
6.96 |
0.87 |
1.30 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1R, M & 0 |
Mean |
150.40 |
2.27 |
6.35 |
0.16 |
0.21 |
0.08 |
16.00 |
21.56 |
±SD |
23.36 |
0.40 |
1.23 |
0.04 |
0.07 |
0.02 |
2.04 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
186.92 |
2.06 |
7.02 |
0.14 |
0.19 |
0.05 |
15.50 |
22.48 |
±SD |
52.68 |
0.53 |
1.09 |
0.04 |
0.04 |
0.03 |
1.17 |
3.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
140.08 |
1.78 |
4.83 |
0.15 |
0.09 |
0.05 |
14.98 |
24.56 |
±SD |
23.05 |
0.73 |
1.73 |
0.05 |
0.02 |
0.01 |
0.53 |
1.98 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
192.10* |
2.06 |
4.98 |
0.17 |
0.25 |
0.05 |
15.92 |
19.34* |
±SD |
30.17 |
0.60 |
2.77 |
0.07 |
0.24 |
0.02 |
1.17 |
2.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, M & 0 |
Mean |
126.60 |
30.52 |
0.58 |
51.60 |
25.60 |
7.74 |
3.47 |
±SD |
15.47 |
2.56 |
0.03 |
3.36 |
2.30 |
0.26 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
123.60 |
33.30 |
0.57 |
60.60 |
30.40 |
7.24* |
3.55 |
±SD |
5.55 |
3.91 |
0.04 |
4.83 |
6.07 |
0.33 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
122.60 |
33.78 |
0.60 |
58.00 |
29.40 |
7.44 |
3.65 |
±SD |
12.92 |
2.83 |
0.03 |
6.71 |
7.73 |
0.22 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
131.00 |
36.04 |
0.59 |
56.00 |
27.00 |
7.58 |
3.68 |
±SD |
19.79 |
4.26 |
0.02 |
9.57 |
6.16 |
0.29 |
0.24 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, M & 0 |
Mean |
61.20 |
111.20 |
125.80 |
0.05 |
9.36 |
6.48 |
±SD |
16.93 |
12.34 |
21.11 |
0.01 |
0.11 |
0.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
47.40 |
93.20 |
120.00 |
0.06 |
9.64 |
6.54 |
±SD |
8.96 |
13.46 |
31.92 |
0.03 |
0.47 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
40.00 |
81.60* |
127.20 |
0.06 |
10.40* |
6.82 |
±SD |
5.96 |
12.30 |
38.01 |
0.03 |
1.05 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
52.20 |
91.80 |
114.80 |
0.06 |
9.94 |
6.62 |
±SD |
24.52 |
18.69 |
28.70 |
0.02 |
0.30 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected) ; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, M & 0 |
Mean |
4.27 |
0.82 |
14.24 |
141.64 |
3.96 |
104.10 |
±SD |
0.30 |
0.09 |
1.19 |
0.94 |
0.25 |
2.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
3.69* |
0.97 |
15.54 |
142.16 |
3.71 |
105.38 |
±SD |
0.38 |
0.12 |
1.83 |
0.53 |
0.15 |
1.40 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
3.79* |
0.97 |
15.77 |
142.44 |
3.86 |
105.78 |
±SD |
0.12 |
0.10 |
1.32 |
0.93 |
0.36 |
1.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
3.90 |
0.95 |
16.82 |
142.76 |
3.85 |
106.40 |
±SD |
0.29 |
0.11 |
1.99 |
0.66 |
0.09 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, F & 0 |
Mean |
102.20 |
48.68 |
0.54 |
76.60 |
78.60 |
7.32 |
3.63 |
±SD |
26.22 |
8.11 |
0.05 |
22.67 |
26.83 |
1.08 |
0.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
121.20 |
51.14 |
0.52 |
67.80 |
59.40 |
7.34 |
3.41 |
±SD |
29.64 |
13.28 |
0.03 |
17.67 |
23.65 |
0.75 |
0.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
103.80 |
44.78 |
0.57 |
75.60 |
43.20 |
7.56 |
3.58 |
±SD |
13.81 |
19.81 |
0.04 |
14.91 |
21.48 |
0.29 |
0.32 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
114.60 |
51.66 |
0.57 |
75.80 |
105.20 |
7.76 |
3.70 |
±SD |
16.44 |
16.16 |
0.07 |
20.44 |
68.28 |
0.58 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, F & 0 |
Mean |
84.60 |
119.40 |
164.40 |
0.03 |
10.06 |
5.92 |
±SD |
14.43 |
14.31 |
75.62 |
0.04 |
1.06 |
0.95 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
113.80 |
143.80 |
420.00 |
0.02 |
9.42 |
5.50 |
±SD |
66.08 |
71.78 |
367.29 |
0.02 |
0.64 |
1.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
96.20 |
99.40 |
305.80 |
0.06 |
10.04 |
6.06 |
±SD |
82.35 |
16.01 |
412.83 |
0.02 |
0.85 |
1.93 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
88.60 |
101.80 |
212.40 |
0.03 |
10.38 |
6.38 |
±SD |
46.69 |
22.65 |
81.17 |
0.04 |
0.91 |
3.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, F & 0 |
Mean |
3.69 |
0.98 |
22.72 |
143.04 |
4.02 |
106.18 |
±SD |
0.50 |
0.11 |
3.79 |
1.34 |
0.81 |
2.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
3.93 |
0.88 |
23.87 |
142.18 |
3.57 |
107.22 |
±SD |
0.66 |
0.14 |
6.20 |
1.47 |
0.28 |
3.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
3.98 |
0.91 |
20.90 |
142.36 |
3.60 |
107.94 |
±SD |
0.40 |
0.16 |
9.25 |
1.61 |
0.33 |
2.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.06 |
0.92 |
24.11 |
142.62 |
3.86 |
107.06 |
±SD |
0.50 |
0.09 |
7.55 |
1.62 |
0.40 |
3.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1R, M & 0 |
Mean |
99.80 |
27.36 |
0.55 |
59.60 |
23.00 |
6.98 |
3.10 |
±SD |
6.53 |
3.92 |
0.02 |
16.21 |
5.52 |
0.26 |
0.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
99.40 |
25.74 |
0.56 |
68.80 |
31.60 |
7.12 |
3.05 |
±SD |
10.53 |
1.19 |
0.03 |
8.76 |
10.78 |
0.11 |
0.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
120.40 |
35.68 |
0.61 |
106.40 |
49.60 |
8.44 |
4.10 |
±SD |
7.16 |
7.57 |
0.02 |
17.07 |
34.09 |
0.56 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
104.00* |
31.42 |
0.59 |
89.20 |
41.60 |
8.04 |
3.70 |
±SD |
13.49 |
2.25 |
0.01 |
16.98 |
11.87 |
0.42 |
0.44 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1R, M & 0 |
Mean |
52.00 |
101.80 |
99.00 |
0.02 |
10.42 |
5.72 |
±SD |
40.34 |
53.17 |
23.40 |
0.02 |
0.37 |
0.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
42.60 |
98.40 |
105.20 |
0.02 |
10.02 |
5.26 |
±SD |
9.86 |
18.49 |
29.84 |
0.01 |
0.15 |
0.50 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
54.00 |
94.00 |
70.80 |
0.02 |
11.20 |
4.20 |
±SD |
28.82 |
36.89 |
40.92 |
0.02 |
0.45 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
53.80 |
103.20 |
69.00 |
0.04 |
10.90 |
4.42 |
±SD |
21.53 |
39.30 |
60.10 |
0.02 |
0.37 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1R, M & 0 |
Mean |
3.88 |
0.80 |
12.77 |
142.82 |
3.56 |
105.48 |
±SD |
0.27 |
0.06 |
1.83 |
0.36 |
0.41 |
0.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
4.07 |
0.75 |
12.01 |
143.16 |
3.59 |
108.06* |
±SD |
0.15 |
0.04 |
0.56 |
0.68 |
0.41 |
1.65 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.34 |
0.95 |
16.65 |
142.62 |
3.45 |
105.76 |
±SD |
0.42 |
0.08 |
3.53 |
0.94 |
0.17 |
1.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
4.34 |
0.85 |
14.66 |
142.26 |
3.62 |
106.40 |
±SD |
0.21 |
0.12 |
1.05 |
1.41 |
0.48 |
2.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 18. SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
5 |
5 |
5 |
5 |
Appearance |
Clear |
5 |
5 |
5 |
5 |
|
Volume (mL) |
Mean |
10.6 |
10.2 |
11.0 |
11.4 |
|
±SD |
0.7 |
1.4 |
0.8 |
0.4 |
||
Chemical Examination |
pH |
Mean |
7.5 |
7.4 |
7.4 |
7.5 |
±SD |
0.0 |
0.4 |
0.5 |
0.0 |
||
Specific Gravity |
Mean |
1.008 |
1.011 |
1.009 |
1.009 |
|
±SD |
0.003 |
0.002 |
0.002 |
0.002 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
2 |
- |
2 |
1 |
|
5 |
3 |
5 |
3 |
4 |
||
Blood (Ery/µL) |
Neg |
5 |
4 |
5 |
5 |
|
Ca80 |
- |
1 |
- |
- |
||
Protein (mg/dL) |
Neg |
3 |
- |
3 |
1 |
|
Trace |
2 |
4 |
1 |
4 |
||
30 |
- |
1 |
1 |
- |
||
Nitrite |
Neg |
4 |
4 |
5 |
1 |
|
Pos |
1 |
1 |
- |
4 |
||
Leucocytes |
Neg |
3 |
- |
3 |
1 |
|
Ca15 |
1 |
1 |
1 |
2 |
||
Ca70 |
1 |
3 |
1 |
2 |
||
Ca125 |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
- |
2 |
1 |
|
>15 |
2 |
5 |
2 |
4 |
||
15 |
3 |
- |
1 |
- |
||
Microscopic Examination |
Epi Cells |
0 |
3 |
4 |
2 |
4 |
0-1 |
1 |
1 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
Casts |
Absent |
4 |
4 |
4 |
5 |
|
Present |
1 |
1 |
1 |
- |
||
Crystals |
Present |
5 |
5 |
5 |
5 |
M:
Male; SD: Standard Deviation; Pos: Positive; Neg: Negative; Ca:
Calculated.
>=:
Greater than or equal to; >: Greater than.
TABLE 18 (Contd…). SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1R, M & 0 |
G4R, M &1000 |
G1R, F & 0 |
G4R, F & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
2 |
5 |
3 |
3 |
Yellow |
3 |
- |
2 |
2 |
||
Appearance |
Clear |
3 |
2 |
4 |
4 |
|
Turbid |
2 |
3 |
1 |
1 |
||
Volume (mL) |
Mean |
6.4 |
8.6 |
7.9 |
7.8 |
|
±SD |
1.7 |
3.1 |
2.2 |
0.8 |
||
Chemical Examination |
pH |
Mean |
6.7 |
7.3 |
6.8 |
7.6 |
±SD |
0.9 |
0.4 |
1.0 |
1.0 |
||
Specific Gravity |
Mean |
1.020 |
1.014 |
1.014 |
1.012 |
|
±SD |
0.007 |
0.002 |
0.007 |
0.008 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.6 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.8 |
||
Bilirubin (mg/dL) |
Neg |
2 |
5 |
5 |
2 |
|
1 |
3 |
- |
- |
3 |
||
Ketones (mg/dL) |
Neg |
1 |
2 |
5 |
5 |
|
5 |
4 |
3 |
- |
- |
||
Blood (Ery/µL) |
Neg |
5 |
5 |
5 |
4 |
|
Ca10 |
- |
- |
- |
1 |
||
Protein (mg/dL) |
Neg |
2 |
5 |
4 |
2 |
|
Trace |
2 |
- |
1 |
- |
||
30 |
1 |
- |
- |
- |
||
100 |
- |
- |
- |
1 |
||
>=300 |
- |
- |
- |
2 |
||
Nitrite |
Neg |
3 |
5 |
5 |
5 |
|
Pos |
2 |
- |
- |
- |
||
Leucocytes |
Neg |
- |
1 |
3 |
2 |
|
Ca15 |
1 |
4 |
2 |
- |
||
Ca70 |
4 |
- |
- |
3 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
1 |
3 |
1 |
|
>15 |
3 |
- |
1 |
3 |
||
15 |
2 |
4 |
1 |
1 |
||
Microscopic Examination\ |
Epi Cells |
0 |
3 |
3 |
2 |
2 |
0-1 |
1 |
2 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
2-3 |
- |
- |
- |
2 |
||
Casts |
Absent |
5 |
2 |
5 |
4 |
|
Present |
- |
3 |
- |
1 |
||
Crystals |
Absent |
- |
2 |
1 |
2 |
|
Present |
5 |
3 |
4 |
3 |
M:
Male; F: Female; R: Recovery; SD: Standard Deviation; Pos: Positive;
Neg: Negative.
Ca: Calculated; >=: Greater than
or equal to; >: Greater than.
TABLE 19. SUMMARY OF VAGINAL SMEAR EXAMINATION RECORD FOR DETERMINATION OF OESTRUS CYCLICITY
Group, Sex & Dose |
Total No. of Females Evaluated |
Females with Complete Regular Cycles |
Females with at least one Irregular Oestrus Cycle |
Average Length of Oestrus Cycle (Days) |
||
G1, F & 0 |
12 |
n |
11 |
1 |
Mean |
4.65 |
% |
91.7 |
8.3 |
±SD |
0.41 |
||
n |
12 |
|||||
G2, F & 111 |
12 |
n |
11 |
0 |
Mean |
4.43 |
% |
91.7 |
0.0 |
±SD |
0.42 |
||
n |
12 |
|||||
G3, F & 333 |
12 |
n |
12 |
0 |
Mean |
4.68 |
% |
100.0 |
0.0 |
±SD |
0.27 |
||
n |
12 |
|||||
G4, F & 1000 |
12 |
n |
11 |
1 |
Mean |
4.53 |
% |
91.7 |
8.3 |
±SD |
0.34 |
||
n |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals.
TABLE 20. SUMMARY OF DELIVERY AND LITTER OBSERVATIONS RECORD
Group, Sex & Dose |
Delivery Record At birth |
||||||||||||||||||
Litter Size (No.) |
Live Pups (No.) |
Dead Pups (No.) |
Cannibalized Pups (No.) |
Sex Ratio (m/f) at Birth |
Live Birth Index (%) |
||||||||||||||
Male |
Female |
Total |
Male |
Female |
Total |
Undetermined |
Male |
Female |
Total |
||||||||||
G1, F & 0 |
Mean |
12.18 |
6.27 |
5.73 |
12.00 |
0.18 |
0.00 |
0.18 |
0.00 |
0.00 |
0.00 |
0.00 |
|
1.14 |
98.86 |
||||
±SD |
2.68 |
1.90 |
1.35 |
2.41 |
0.40 |
0.00 |
0.40 |
0.00 |
0.00 |
0.00 |
0.00 |
0.42 |
2.54 |
||||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
||||||
G2, F & 111 |
Mean |
12.20 |
|
6.00 |
6.00 |
12.00 |
|
0.10 |
0.10 |
0.20 |
|
0.00 |
0.00 |
0.00 |
0.00 |
|
1.12 |
|
98.70 |
±SD |
3.29 |
1.94 |
1.89 |
3.09 |
0.32 |
0.32 |
0.42 |
0.00 |
0.00 |
0.00 |
0.00 |
0.57 |
2.76 |
||||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
||||||
G3, F & 333 |
Mean |
10.90 |
|
5.30 |
5.50 |
10.80 |
|
0.10 |
0.00 |
0.10 |
|
0.00 |
0.00 |
0.00 |
0.00 |
|
1.00 |
|
99.41 |
±SD |
2.77 |
2.00 |
1.27 |
2.53 |
0.32 |
0.00 |
0.32 |
0.00 |
0.00 |
0.00 |
0.00 |
0.39 |
1.86 |
||||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
||||||
G4, F & 1000 |
Mean |
12.82 |
|
6.36 |
6.09 |
12.45 |
|
0.18 |
0.18 |
0.36 |
|
0.00 |
0.00 |
0.00 |
0.00 |
|
1.16 |
|
96.57 |
±SD |
1.99 |
2.11 |
1.64 |
2.54 |
0.40 |
0.60 |
0.92 |
0.00 |
0.00 |
0.00 |
0.00 |
0.71 |
9.11 |
||||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams; m/f: Male/Female; %: Percentage.
TABLE 20 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS
Group, Sex & Dose weight/day) |
LD 1 to 4 |
Sex Ratio (m/f) on LD 4 |
Pup Survival Index (%) [LD 1 to 4] |
|||||||||||||
Live Pups (No.) |
Dead Pups (No.) |
Cannibalized Pups (No.) |
||||||||||||||
Male |
Female |
Total |
Male |
Female |
Total |
Male |
Female |
Total |
||||||||
G1, F & 0 |
Mean |
6.27 |
5.73 |
12.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.14 |
100.00 |
||||
±SD |
1.90 |
1.35 |
2.41 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.42 |
0.00 |
|||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
|||||
G2, F & 111 |
Mean |
6.00 |
6.00 |
12.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.12 |
100.00 |
||||
±SD |
1.94 |
1.89 |
3.09 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.57 |
0.00 |
|||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||
G3, F & 333 |
Mean |
5.30 |
5.50 |
10.80 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.00 |
100.00 |
||||
±SD |
2.00 |
1.27 |
2.53 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.39 |
0.00 |
|||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||
G4, F & 1000 |
Mean |
6.36 |
6.09 |
12.45 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.16 |
100.00 |
||||
±SD |
2.11 |
1.64 |
2.54 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.71 |
0.00 |
|||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams; m/f: Male/Female; %: Percentage.
TABLE 20 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS
Group, Sex & Dose |
Pups Sacrificed for Litter Standardization / Hormonal analysis (No.) |
Live Pups (No.) on LD 4 after Litter Standardization / Hormonal analysis (No.) |
LD 5 to 7 |
Sex Ratio (m/f) on LD 7 |
Pup Survival Index (%) [LD 5 to 7] |
|||||||||||||||||||
Live Pups (No.) |
Dead Pups (No.) |
Cannibalized (No.) |
||||||||||||||||||||||
Male |
Female |
Total |
Male |
Female |
Total |
Male |
Female |
Total |
Male |
Female |
Total |
Male |
Female |
Total |
||||||||||
G1, F & 0 |
Mean |
0.00 |
1.09 |
1.09 |
6.27 |
4.64 |
10.91 |
6.27 |
4.64 |
10.91 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.55 |
100.00 |
||||||
±SD |
0.00 |
1.04 |
1.04 |
1.90 |
1.36 |
1.58 |
1.90 |
1.36 |
1.58 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.86 |
0.00 |
|||||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
|||||||
G2, F & 111 |
Mean |
0.00 |
1.20 |
1.20 |
6.00 |
4.80 |
10.80 |
6.00 |
4.80 |
10.80 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.37 |
100.00 |
||||||
±SD |
0.00 |
1.03 |
1.03 |
1.94 |
1.23 |
2.20 |
1.94 |
1.23 |
2.20 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.62 |
0.00 |
|||||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||||
G3, F & 333 |
Mean |
0.00 |
0.70 |
0.70 |
5.30 |
4.80 |
10.10 |
5.30 |
4.80 |
10.10 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.21 |
100.00 |
||||||
±SD |
0.00 |
0.95 |
0.95 |
2.00 |
1.03 |
1.73 |
2.00 |
1.03 |
1.73 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.67 |
0.00 |
|||||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||||
G4, F & 1000 |
Mean |
0.00 |
1.64 |
1.64 |
6.36 |
4.45 |
10.82 |
6.36 |
4.45 |
10.82 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
2.07 |
100.00 |
||||||
±SD |
0.00 |
0.81 |
0.81 |
2.11 |
1.57 |
1.99 |
2.11 |
1.57 |
1.99 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
2.39 |
0.00 |
|||||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams; LD: Lactation Day; m/f: Male/Female.
TABLE 20 (Contd…). SUMMARY RECORD OF DELIVERY AND LITTER OBSERVATIONS
Group, Sex & Dose weight/day) |
LD 8 to 13 |
Sex Ratio (m/f) on LD 13 |
Pup Survival Index (%) [LD 8 to 13] |
|||||||||||||
Live Pups (No.) |
Dead Pups (No.) |
Cannibalized (No.) |
||||||||||||||
Male |
Female |
Total |
Male |
Female |
Total |
Male |
Female |
Total |
||||||||
G1, F & 0 |
Mean |
6.27 |
4.64 |
10.91 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.55 |
100.00 |
||||
±SD |
1.90 |
1.36 |
1.58 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.86 |
0.00 |
|||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
|||||
G2, F & 111 |
Mean |
6.00 |
4.80 |
10.80 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.37 |
100.00 |
||||
±SD |
1.94 |
1.23 |
2.20 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.62 |
0.00 |
|||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||
G3, F & 333 |
Mean |
5.30 |
4.80 |
10.10 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
1.21 |
100.00 |
||||
±SD |
2.00 |
1.03 |
1.73 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.67 |
0.00 |
|||||
n |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
|||||
G4, F & 1000 |
Mean |
6.36 |
4.45 |
10.82 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
2.07 |
100.00 |
||||
±SD |
2.11 |
1.57 |
1.99 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
2.39 |
0.00 |
|||||
n |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams; LD: Lactation Day; m/f: Male/Female; %: Percentage.
TABLE 21. SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose |
No. of Males with Evidence of Mating |
Male Mating Index (%) |
No. of Males Capable of Impregnating a Female |
Male Fertility Index (%) |
|
G1, M & 0 |
12 (12) |
100.0 |
11 (12) |
91.7 |
|
G2, M & 111 |
12 (12) |
100.0 |
10 (12) |
83.3 |
|
G3, M & 333 |
12 (12) |
100.0 |
10 (12) |
83.3 |
|
G4, M & 1000 |
12 (12) |
100.0 |
11 (12) |
91.7 |
M: Male.
TABLE 21 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose (mg/kg body weight/day) |
Cohabitation Record and Pre-coital Interval (Mean Time of Mating) |
|
Gestational Length (duration of pregnancy) |
||||
Pre-coital Interval (Days) |
Conceiving Days (1 to 5) |
Conceiving Days (More than 5 days) |
Gestation Length (Days) |
||||
G1, F & 0 |
Mean |
3.58 |
n |
8 |
4 |
22.55 |
|
SD |
3.80 |
% |
66.67 |
33.33 |
0.52 |
||
N |
12 |
11 |
|||||
G2, F & 111 |
Mean |
3.75 |
n |
9 |
3 |
22.20 |
|
SD |
4.45 |
% |
75 |
25 |
0.63 |
||
N |
12 |
10 |
|||||
G3, F & 333 |
Mean |
4.58 |
n |
8 |
4 |
22.50 |
|
SD |
5.00 |
% |
66.67 |
33.33 |
0.53 |
||
N |
12 |
10 |
|||||
G4, F & 1000 |
Mean |
4.67 |
n |
8 |
4 |
22.36 |
|
SD |
5.50 |
% |
66.67 |
33.33 |
0.50 |
||
N |
12 |
11 |
F: Female; SD: Standard Deviation; n: Number of females with evidence of mating (pre-coital interval); n: Number of pregnant females (gestation length).
TABLE 21 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose (mg/kg body weight/day) |
Female Mating Index (%) |
Female Fertility Index (%) |
|||
No. of Females with Evidence of Mating (No. of Females used for Mating) |
Female Mating Index (%) |
No. of Females Confirmed as Fertile |
Female Fertility Index (%) |
||
G1, F & 0 |
12 (12) |
100.0 |
11 (12) |
91.7 |
|
G2, F & 111 |
12 (12) |
100.0 |
10 (12) |
83.3 |
|
G3, F & 333 |
12 (12) |
100.0 |
10 (12) |
83.3 |
|
G4, F & 1000 |
12 (12) |
100.0 |
11 (12) |
91.7 |
F: Female.
TABLE 21 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose mg/kg body weight/day) |
Female Fecundity or Pregnancy Index (%) |
Gestation Index (%) |
|||||
No. of Pregnant Females |
No. of Females Confirmed with Mating |
Female Fecundity or Pregnancy Index (%) |
Females with Live Born Pups at Parturition |
No. of Females with Evidence of Pregnancy |
Gestation Index (%) |
||
G1, F & 0 |
11 |
12 |
91.7 |
11 |
11 |
100.0 |
|
G2, F & 111 |
10 |
12 |
83.3 |
10 |
10 |
100.0 |
|
G3, F & 333 |
10 |
12 |
83.3 |
10 |
10 |
100.0 |
|
G4, F & 1000 |
11 |
12 |
91.7 |
11 |
11 |
100.0 |
F: Female.
TABLE 21 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose (mg/kg body weight/day) |
Parturition index (%) |
||
No. of Females Littered |
No. of Females with evidence of pregnancy |
Parturition index (%) |
|
G1, F & 0 |
11 |
11 |
100.0 |
G2, F & 111 |
10 |
10 |
100.0 |
G3, F & 333 |
10 |
10 |
100.0 |
G4, F & 1000 |
11 |
11 |
100.0 |
F: Female.
TABLE 21 (Contd…). SUMMARY RECORD OF REPRODUCTIVE PERFORMANCE
Group, Sex & Dose weight/day) |
|
Post-implantation Loss (%) |
|
Post-natal Loss (%) |
||||
No. of Implantations |
No. of Viable (Live) Pups |
Post-implantation Loss (No.) |
Post-implantation Loss (%) |
Total No. of Pups Found Dead/ Cannibalized during lactation period |
Post-natal Loss (%) |
|||
G1, F & 0 |
Mean |
12.45 |
12.00 |
0.45 |
3.70 |
|
0.00 |
0.00 |
±SD |
2.42 |
2.41 |
0.52 |
4.40 |
|
0.00 |
0.00 |
|
n |
11 |
11 |
11 |
11 |
|
11 |
11 |
|
G2, F & 111 |
Mean |
12.70 |
12.00 |
0.70 |
6.02 |
|
0.00 |
0.00 |
±SD |
2.75 |
3.09 |
1.06 |
9.67 |
|
0.00 |
0.00 |
|
n |
10 |
10 |
10 |
10 |
|
10 |
10 |
|
G3, F & 333 |
Mean |
11.00 |
10.80 |
0.20 |
1.50 |
|
0.00 |
0.00 |
±SD |
2.75 |
2.53 |
0.42 |
3.25 |
|
0.00 |
0.00 |
|
n |
10 |
10 |
10 |
10 |
|
10 |
10 |
|
G4, F & 1000 |
Mean |
13.27 |
12.45 |
0.82 |
6.72 |
|
0.00 |
0.00 |
±SD |
1.74 |
2.54 |
1.40 |
11.56 |
|
0.00 |
0.00 |
|
n |
11 |
11 |
11 |
11 |
|
11 |
11 |
F: Female; n: Number of Dams.
TABLE 22. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1, M & 0 |
Mean |
0.0667 |
0.2891 |
0.7915 |
3.3315 |
1.4198 |
1.3943 |
2.9537 |
2.1193 |
±SD |
0.0045 |
0.0466 |
0.2701 |
0.3035 |
0.1420 |
0.2048 |
0.2510 |
0.0321 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
0.0719 |
0.3589 |
0.8023 |
3.4284 |
1.4112 |
1.5033 |
2.8196 |
2.1336 |
±SD |
0.0094 |
0.0292 |
0.0928 |
0.1782 |
0.1365 |
0.1061 |
0.1723 |
0.0957 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
0.0709 |
0.4450* |
0.8041 |
3.3728 |
1.4195 |
1.4754 |
2.8317 |
2.1467 |
±SD |
0.0060 |
0.0665 |
0.1455 |
0.2771 |
0.1776 |
0.1560 |
0.1507 |
0.0446 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0716 |
0.4129* |
0.8155 |
3.3454 |
1.5221 |
1.5218 |
3.0082 |
2.2033 |
±SD |
0.0115 |
0.1013 |
0.1404 |
0.2101 |
0.1812 |
0.3979 |
0.7565 |
0.1355 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
G1, M & 0 |
Mean |
10.0491 |
1.1499 |
1.6300 |
1.9467 |
0.0208 |
0.0296 |
±SD |
1.6192 |
0.1975 |
0.4468 |
0.1258 |
0.0014 |
0.0017 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
10.3930 |
1.1988 |
1.6027 |
2.0659 |
0.0197 |
0.0290 |
±SD |
0.4389 |
0.2552 |
0.3454 |
0.1175 |
0.0013 |
0.0020 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
10.6576 |
1.3430 |
1.7846 |
2.0478 |
0.0203 |
0.0301 |
±SD |
0.7376 |
0.3501 |
0.3700 |
0.1024 |
0.0009 |
0.0013 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
10.8065 |
1.2209 |
1.9124 |
2.0837 |
0.0205 |
0.0305 |
±SD |
2.8155 |
0.3931 |
0.5906 |
0.1492 |
0.0015 |
0.0023 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
0.0741 |
0.2781 |
0.7048 |
0.1738 |
0.5901 |
1.1848 |
±SD |
0.0083 |
0.0317 |
0.0646 |
0.0299 |
0.1167 |
0.1262 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
0.0884 |
0.2632 |
0.7503 |
0.1432* |
0.5097 |
1.1940 |
±SD |
0.0110 |
0.0345 |
0.1289 |
0.0332 |
0.1138 |
0.0729 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
0.0728 |
0.2267* |
0.6584 |
0.1291* |
0.5413 |
1.2001 |
±SD |
0.0094 |
0.0282 |
0.1051 |
0.0193 |
0.0886 |
0.0513 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
0.0775 |
0.2179* |
0.6109 |
0.1466* |
0.5283 |
1.3318 |
±SD |
0.0093 |
0.0063 |
0.0413 |
0.0190 |
0.1008 |
0.3482 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 22).
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
2.2668 |
2.0179 |
11.5641 |
1.2626 |
0.0179 |
0.0266 |
±SD |
0.1164 |
0.0746 |
0.5339 |
0.1185 |
0.0011 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
2.0463* |
2.0056 |
12.5985 |
1.5260 |
0.0183 |
0.0272 |
±SD |
0.1081 |
0.1131 |
2.0359 |
0.2954 |
0.0014 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
2.0269* |
1.9917 |
10.1148 |
1.3551 |
0.0176 |
0.0265 |
±SD |
0.0937 |
0.0552 |
1.8164 |
0.1082 |
0.0008 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
1.9230* |
2.0216 |
10.2708 |
1.3780 |
0.0180 |
0.0275 |
±SD |
0.0912 |
0.0446 |
1.3180 |
0.1188 |
0.0010 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1R, M & 0 |
Mean |
0.0671 |
0.2367 |
0.8804 |
3.3055 |
1.6954 |
1.6355 |
2.2619 |
2.0448 |
±SD |
0.0080 |
0.0348 |
0.0907 |
0.1930 |
0.0763 |
0.1477 |
0.3680 |
0.1172 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0638 |
0.2709 |
0.7442* |
3.4656 |
1.6882 |
1.6050 |
2.3506 |
2.0483 |
±SD |
0.0051 |
0.0738 |
0.0528 |
0.1133 |
0.0690 |
0.3581 |
0.3464 |
0.1621 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
12.6730 |
1.3824 |
1.8300 |
2.0437 |
0.0207 |
0.0299 |
±SD |
1.2027 |
0.2475 |
0.4858 |
0.5420 |
0.0009 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
12.5717 |
1.6038 |
1.8342 |
1.9398 |
0.0210 |
0.0306 |
±SD |
1.2099 |
0.1130 |
0.4887 |
0.0584 |
0.0011 |
0.0008 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
0.0706 |
0.2511 |
0.6464 |
0.1265 |
0.6499 |
1.0512 |
±SD |
0.0064 |
0.0443 |
0.0886 |
0.0164 |
0.0920 |
0.0882 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0702 |
0.2467 |
0.6261 |
0.1543* |
0.6334 |
1.0135 |
±SD |
0.0121 |
0.0337 |
0.1113 |
0.0105 |
0.0853 |
0.0746 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 22 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, F & 0 |
Mean |
1.9138 |
2.0075 |
9.6308 |
1.8480 |
0.0185 |
0.0278 |
±SD |
0.0978 |
0.0986 |
0.9760 |
0.0946 |
0.0009 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.8218 |
1.9767 |
8.6614 |
2.0609 |
0.0193 |
0.0271 |
±SD |
0.1551 |
0.0844 |
1.7719 |
0.4014 |
0.0014 |
0.0006 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 23. SUMMARY
OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1, M & 0 |
Mean |
440.14 |
0.0150 |
0.0648 |
0.1748 |
0.7637 |
0.3257 |
0.3099 |
±SD |
38.09 |
0.0018 |
0.0115 |
0.0484 |
0.1095 |
0.0493 |
0.0251 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G2, M & 111 |
Mean |
433.53 |
0.0162 |
0.0812 |
0.1809 |
0.7928 |
0.3262 |
0.3390 |
±SD |
29.89 |
0.0021 |
0.0090 |
0.0188 |
0.0447 |
0.0319 |
0.0185 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G3, M & 333 |
Mean |
437.73 |
0.0159 |
0.0995* |
0.1797 |
0.7734 |
0.3250 |
0.3314 |
±SD |
26.65 |
0.0016 |
0.0135 |
0.0302 |
0.0792 |
0.0413 |
0.0427 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, M & 1000 |
Mean |
443.94 |
0.0156 |
0.0891* |
0.1779 |
0.7570 |
0.3432 |
0.3304 |
±SD |
38.78 |
0.0013 |
0.0124 |
0.0187 |
0.0592 |
0.0298 |
0.0626 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, M & 0 |
Mean |
0.6591 |
0.4745 |
2.2336 |
0.2614 |
0.3768 |
0.4360 |
0.0047 |
0.0067 |
±SD |
0.0371 |
0.0334 |
0.2239 |
0.0389 |
0.1233 |
0.0428 |
0.0003 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
0.6380 |
0.4818 |
2.3449 |
0.2758 |
0.3681 |
0.4668 |
0.0044 |
0.0067 |
±SD |
0.0606 |
0.0272 |
0.0585 |
0.0505 |
0.0681 |
0.0350 |
0.0003 |
0.0006 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
0.6350 |
0.4812 |
2.3924 |
0.3052 |
0.4081 |
0.4594 |
0.0046 |
0.0069 |
±SD |
0.0467 |
0.0237 |
0.2415 |
0.0710 |
0.0824 |
0.0376 |
0.0001 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
0.6545 |
0.4865 |
2.3426 |
0.2767 |
0.4271 |
0.4575 |
0.0045 |
0.0069 |
±SD |
0.1286 |
0.0618 |
0.4199 |
0.0940 |
0.1161 |
0.0285 |
0.0002 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
305.54 |
0.0242 |
0.0912 |
0.2307 |
0.0571 |
0.1938 |
0.3872 |
±SD |
21.99 |
0.0035 |
0.0163 |
0.0360 |
0.0100 |
0.0422 |
0.0618 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
314.85 |
0.0286 |
0.0853 |
0.2428 |
0.0458* |
0.1635 |
0.3854 |
±SD |
19.21 |
0.0044 |
0.0142 |
0.0457 |
0.0115 |
0.0448 |
0.0220 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
302.78 |
0.0236 |
0.0730 |
0.2142 |
0.0431* |
0.1801 |
0.3879 |
±SD |
22.49 |
0.0038 |
0.0045 |
0.0429 |
0.0092 |
0.0352 |
0.0151 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
306.64 |
0.0245 |
0.0690* |
0.1938 |
0.0483 |
0.1749 |
0.4241 |
±SD |
25.44 |
0.0033 |
0.0062 |
0.0238 |
0.0080 |
0.0430 |
0.1222 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 23).
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
0.7409 |
0.6583 |
3.7703 |
0.4138 |
0.0058 |
0.0087 |
±SD |
0.0909 |
0.0663 |
0.3600 |
0.0696 |
0.0003 |
0.0005 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
0.6618 |
0.6488 |
4.0668 |
0.4903 |
0.0059 |
0.0087 |
±SD |
0.0563 |
0.0584 |
0.6665 |
0.0770 |
0.0002 |
0.0009 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
0.6560 |
0.6443 |
3.2646 |
0.4388 |
0.0057 |
0.0088 |
±SD |
0.0476 |
0.0330 |
0.5652 |
0.0452 |
0.0002 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
0.6097* |
0.6402 |
3.2355 |
0.4353 |
0.0057 |
0.0090 |
±SD |
0.0642 |
0.0516 |
0.3329 |
0.0373 |
0.0008 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1R, M & 0 |
Mean |
496.58 |
0.0136 |
0.0476 |
0.1785 |
0.6684 |
0.3430 |
0.3320 |
±SD |
40.88 |
0.0022 |
0.0051 |
0.0257 |
0.0554 |
0.0286 |
0.0478 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
502.58 |
0.0127 |
0.0538 |
0.1482* |
0.6902 |
0.3358 |
0.3184 |
±SD |
12.09 |
0.0010 |
0.0137 |
0.0126 |
0.0356 |
0.0088 |
0.0643 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
0.4554 |
0.4147 |
2.5665 |
0.2783 |
0.3746 |
0.4088 |
0.0042 |
0.0060 |
±SD |
0.0586 |
0.0488 |
0.3239 |
0.0415 |
0.1185 |
0.0840 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.4682 |
0.4080 |
2.4984 |
0.3193 |
0.3643 |
0.3862 |
0.0042 |
0.0061 |
±SD |
0.0730 |
0.0361 |
0.1858 |
0.0248 |
0.0941 |
0.0153 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
308.17 |
0.0229 |
0.0822 |
0.2106 |
0.0410 |
0.2112 |
0.3432 |
±SD |
16.88 |
0.0016 |
0.0185 |
0.0336 |
0.0043 |
0.0292 |
0.0498 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
311.82 |
0.0225 |
0.0791 |
0.2015 |
0.0495* |
0.2026 |
0.3256 |
±SD |
12.71 |
0.0037 |
0.0102 |
0.0405 |
0.0029 |
0.0205 |
0.0293 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 23 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, F & 0 |
Mean |
0.6217 |
0.6518 |
3.1221 |
0.6009 |
0.0060 |
0.0090 |
±SD |
0.0295 |
0.0166 |
0.2213 |
0.0411 |
0.0002 |
0.0005 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.5840 |
0.6342 |
2.7664 |
0.6616 |
0.0062 |
0.0087 |
±SD |
0.0386 |
0.0217 |
0.4774 |
0.1320 |
0.0003 |
0.0002 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 24. SUMMARY OF SERUM T4 HORMONE LEVELS (ng/mL) RECORD - ADULTS
Group, Sex & Dose (mg/kg body weight/day) |
Serum T4 Levels (ng/mL) |
|
G1, M & 0 |
Mean |
78.813 |
±SD |
7.616 |
|
n |
12 |
|
G2, M & 111 |
Mean |
67.002* |
±SD |
12.097 |
|
n |
12 |
|
G3, M & 333 |
Mean |
79.275 |
±SD |
10.083 |
|
n |
12 |
|
G4, M & 1000 |
Mean |
77.258 |
±SD |
13.137 |
|
n |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 25. SUMMARY RECORD OF PUP OBSERVATIONS DURING POSTNATAL PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
At Birth (PND 1) |
PND 1 to 4 |
Pups Sacrificed for Blood Collection on PND 4 (No.)* |
PND 5 to 7$ |
PND 8 to 13$ |
|
G1, F & 0 |
No. of Dams# |
11 |
11 |
6 |
11 |
11 |
No. of Live Pups |
132 |
132 |
11 |
120 |
120 |
|
Pup Observation/ No. of Pups observed |
N/132 |
N/132 |
- |
N/120 |
N/120 |
|
G2, F & 111 |
No. of Dams# |
10 |
10 |
6 |
10 |
10 |
No. of Live Pups |
120 |
120 |
12 |
108 |
108 |
|
Pup Observation/ No. of Pups observed |
N/120 |
N/120 |
- |
N/108 |
N/108 |
|
G3, F & 333 |
No. of Dams# |
10 |
10 |
4 |
10 |
10 |
No. of Live Pups |
108 |
108 |
7 |
101 |
101 |
|
Pup Observation/ No. of Pups observed |
N/108 |
N/108 |
- |
N/101 |
N/101 |
|
G4, F & 1000 |
No. of Dams# |
11 |
11 |
9 |
11 |
11 |
No. of Live Pups |
137 |
137 |
18 |
119 |
119 |
|
Pup Observation/ No. of Pups observed |
N/137 |
N/137 |
- |
N/119 |
N/119 |
F: Female; N: Normal; PND: Postnatal Day; #: Dams confirmed with littering.
*: Pups selected for blood collection from dams with litter size of more than 10; $: Pups sacrificed on PND 4 were excluded.
TABLE 26. SUMMARY RECORD OF MEAN PUP WEIGHT (g) PER LITTER
Group, Sex & Dose (mg/kg body weight/day) |
PND 1 |
PND 4 |
PND 7 |
PND 13 |
||||||||
Mean Pup Weight (g) |
Mean Pup Weight (g) |
|
Mean Pup Weight (g) |
|
Mean Pup Weight (g) |
|||||||
Male |
Female |
|
Male |
Female |
|
Male |
Female |
|
Male |
Female |
||
G1, F & 0 |
Mean |
6.79 |
6.23 |
|
10.88 |
10.35 |
|
14.87 |
14.37 |
|
28.44 |
27.57 |
±SD |
0.04 |
0.08 |
0.12 |
0.10 |
0.11 |
0.13 |
0.36 |
0.46 |
||||
n |
11 (69) |
11 (63) |
|
11 (69) |
11 (63) |
|
11 (69) |
11 (51) |
|
11 (69) |
11 (51) |
|
G2, F & 111 |
Mean |
6.79 |
6.28 |
|
10.89 |
10.35 |
|
14.88 |
14.39 |
|
28.29 |
27.56 |
±SD |
0.08 |
0.14 |
0.12 |
0.11 |
0.17 |
0.21 |
0.37 |
0.51 |
||||
n |
10 (60) |
10 (60) |
|
10 (60) |
10 (60) |
|
10 (60) |
10 (48) |
|
10 (60) |
10 (48) |
|
G3, F & 333 |
Mean |
6.84 |
6.30 |
|
10.91 |
10.37 |
|
14.91 |
14.42 |
|
28.50 |
27.90 |
±SD |
0.08 |
0.09 |
0.10 |
0.12 |
0.15 |
0.17 |
0.46 |
0.42 |
||||
n |
10 (53) |
10 (55) |
|
10 (53) |
10 (55) |
|
10 (53) |
10 (48) |
|
10 (53) |
10 (48) |
|
G4, F & 1000 |
Mean |
6.79 |
6.23 |
|
10.87 |
10.32 |
|
14.88 |
14.36 |
|
28.31 |
27.39 |
±SD |
0.06 |
0.07 |
0.09 |
0.11 |
0.12 |
0.17 |
0.44 |
0.37 |
||||
n |
11 (70) |
11 (67) |
|
11 (70) |
11 (67) |
|
11 (70) |
11 (49) |
|
11 (70) |
11 (49) |
F: Female; SD: Standard Deviation; n: Number of Litters (number of pups); PND: Postnatal Day.
TABLE 27. SUMMARY RECORD OF MEAN PUP ANOGENITAL DISTANCE (AGD) MEASUREMENT (mm) AND ANOGENITAL DISTANCE (AGD) RATIO PER LITTER ON POSTNATAL DAY 4
Group & Dose (mg/kg body weight/day) |
AGD Measurement (mm) |
AGD Ratio |
||||
Male |
Female |
Male |
Female |
|||
G1, F & 0 |
Mean |
4.81 |
2.45 |
2.17 |
1.13 |
|
±SD |
0.12 |
0.08 |
0.05 |
0.03 |
||
n |
11 (69) |
11 (63) |
|
11 (69) |
11 (63) |
|
G2, F & 111 |
Mean |
4.89 |
2.45 |
2.21 |
1.12 |
|
±SD |
0.09 |
0.08 |
0.03 |
0.03 |
||
n |
10 (60) |
10 (60) |
|
10 (60) |
10 (60) |
|
G3, F & 333 |
Mean |
4.95* |
2.46 |
2.23* |
1.13 |
|
±SD |
0.07 |
0.03 |
0.03 |
0.02 |
||
n |
10 (53) |
10 (55) |
|
10 (53) |
10 (55) |
|
G4, F & 1000 |
Mean |
4.89 |
2.50 |
2.21* |
1.15 |
|
±SD |
0.09 |
0.09 |
0.04 |
0.04 |
||
n |
11 (70) |
11 (67) |
|
11 (70) |
11 (67) |
F: Female; SD: Standard Deviation; n: Number of Litters (number of pups); AGD: Anogenital Distance.
*: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 28. SUMMARY RECORD OF OBSERVATION OF MALE PUPS FOR RETENTION OF NIPPLE/AREOLAE (No.) RECORD
Group & Dose |
|
Mean No. of Pups with Retention of Nipples/ Areolae on Postnatal Day 13 |
G1 & 0 |
Mean |
0.00 |
±SD |
0.00 |
|
n |
11 (69) |
|
G2 & 111 |
Mean |
0.00 |
±SD |
0.00 |
|
n |
10 (60) |
|
G3 & 333 |
Mean |
0.00 |
±SD |
0.00 |
|
n |
10 (53) |
|
G4 & 1000 |
Mean |
0.00 |
±SD |
0.00 |
|
n |
11 (70) |
F: Female; SD: Standard Deviation; n: Number of Litters (number of male pups).
TABLE 29. SUMMARY OF SERUM T4 HORMONE LEVELS (ng/mL) RECORD - POSTNATAL DAY (PND) 13 PUPS
Group & Dose (mg/kg body weight/day) |
Serum T4 Levels (ng/mL) |
|
G1, F & 0 |
Mean |
71.557 |
±SD |
6.196 |
|
n |
11 |
|
G2, F & 111 |
Mean |
58.207* |
±SD |
6.124 |
|
n |
10 |
|
G3, F & 333 |
Mean |
55.550* |
±SD |
3.863 |
|
n |
10 |
|
G4, F & 1000 |
Mean |
60.962* |
±SD |
6.316 |
|
n |
11 |
F: Female; SD: Standard Deviation; n: Number of Litters (number of pups); PND: Postnatal Day
Note: No pups were sacrificed from group G4, as the litter size is equal to or less than 10.
*: Statistically significant (P<0.05) change than the vehicle control group.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted on 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 5,12-dihydroquino[2,3-b]acridine-7,14-dione
- EC Number:
- 213-879-2
- EC Name:
- 5,12-dihydroquino[2,3-b]acridine-7,14-dione
- Cas Number:
- 1047-16-1
- Molecular formula:
- C20H12N2O2
- IUPAC Name:
- 5,12-dihydroquino[2,3-b]acridine-7,14-dione
- Test material form:
- solid: nanoform
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29ºC)
- Solubility and stability of the test substance in the solvent/vehicle: The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies.
The test item was stable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl cellulose with the concentrations of 5 mg/mL and 100 mg/mL.
FORM AS APPLIED IN THE TEST: The test item or vehicle were administered to the animals through the oral (gavage) route once daily
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is one of the standard laboratory rodent species used for toxicity assessment and also recommended by various regulatory authorities.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Hylasco Biotechnology India Pvt. Ltd, Charles River Technology Licensee, CPCSEA (Committee for the Purpose of Control and Supervision of Experiments on Animals) Registration No.: 1808/PO/RcBt/S/15/CPCSEA
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: Males: 254.36 to 291.64 g; Females: 200.54 to 211.92 g
- Housing: Animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
During acclimatization, two animals of same sex were housed.
i. Main Group Animals:
- Pre mating: Per cage two animals of same sex and group were housed.
- Cohabitation Period (mating): Per cage two animals (one male and one female) of same group were housed.
- Post-mating: After confirmation on presence of sperm in the vaginal smear (Day 0 of pregnancy), the mated pairs were separated. Males were housed with their former cage mates while females were housed individually. Sterilized paper shreds were provided as a nesting material for main group females from gestation day 20 onwards.
ii. Recovery Group Animals:
- Maximum of two animals per cage per group of same sex were housed, tunnels were provided as enrichment for the animals which were housed individually.
- Diet: Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG) was provided ad libitum to the animals throughout the experimental period.
- Water: Water was provided ad libitum throughout the experimental period. Deep bore-well water passed through reverse osmosis unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: 5 days
DETAILS OF FOOD AND WATER QUALITY: Analysis of food and water qaulity included as annexures in the study report.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 to 22.9 Degree Centigrade
- Humidity (%): 48 to 63%,
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 24 June 2021; To: 16 September 2021
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- The test item or vehicle were administered to the animals through the oral (gavage) route once daily.
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% w/v CMC (carboxymethyl cellulose)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): The test item was insoluble in distilled water and uniformly suspended in 0.5% w/v Carboxy Methyl Cellulose at the concentration of 100 mg/mL (the highest dose concentration selected for the study considering the dose volume of 10 mL/kg body weight) as per in-house solubility/suspendibility test results.
Hence, 0.5% w/v Carboxymethyl Cellulose was used as vehicle for test item formulations in consultation with sponsor.
0.5% w/v Carboxymethyl Cellulose is a routinely used and universally accepted vehicle of choice for the oral toxicity studies
- Concentration in vehicle: The concentrations of of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively
- Amount of vehicle (if gavage): 10mL/Kg body weight
- Batch no.: SLCH1520, expiry date: September 2026; Make Sigma Aldrich
- Purity: Medium viscocity grade - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The Dose formulation samples of the test item were analyzed for homogeneity and dose concentration by UV-Vis Method and the results are found within the range of 85 to 115% of the nominal concentration and the %RSD is <15%
Homogeneity and dose formulation analysis for dose concentration verification was performed during week 1 and week 5 of the treatment. The samples were collected in duplicates (5 mL each) from top, middle and bottom layers from low, mid and high dose concentrations and in duplicates from single layer from vehicle control.
The prepared test item formulations were stirred using magnetic stirrer during sampling.
The mean obtained results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%. - Duration of treatment / exposure:
- Males: 31 Days
Females: The females were treated for a two-week pre-mating period (14-days), during mating, pregnancy (gestation) and up to lactation day 13 (ranging from a total period of 50 to 62 days).
The females with positive mating signal, but no-evidence of pregnancy / littering were treated during two-week pre-mating period, during mating and further 24 days from the day of positive mating signal (group G1 - one female until experimental day 39; group G2 - one female until experimental day 52, one female until experimental day 46; G3 - two females until experimental day 49; group G4 - one female until experimental day 39).
Recovery group animals: 52 Days - Frequency of treatment:
- Once Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: mg/kg body weight/day
- Remarks:
- Vehicle Control
- Dose / conc.:
- 111 other: mg/kg body weight/day
- Remarks:
- Low Dose
- Dose / conc.:
- 333 other: mg/kg body weight/day
- Remarks:
- Mid Dose
- Dose / conc.:
- 1 000 other: mg/kg body weight/day
- Remarks:
- High Dose
- No. of animals per sex per dose:
- Main Group: 24 (12 Males + 12 Females)
Recovery Group: 10 (5 Males + 5 Females) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: There was no information or data available from repeated dose/reproduction toxicity and teratology studies for the test item.
The doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups for the dose range finding study (BIO-DTX 056) in consultation with the sponsor.
There were no test item-related related changes noted in any of the systemic, reproduction and developmental parameters up to the dose level of 1000 mg/kg body weight/day in the Dose Range Finding Study (BIO-DTX 056).
Hence, the same doses of 0, 111, 333 and 1000 mg/kg body weight/day were selected as control, low, mid and high dose groups respectively, for the present study in consultation with the sponsor.
- Rationale for animal assignment: The animals were weighed and arranged in ascending order of their body weights. These body weight stratified animals were distributed to all the main and recovery groups using Microsoft Excel Spreadsheet, such that body weight variation of animals selected for the study does not exceed ±20% (Males: -6.80 to 11.14%; Females: -12.58 to 8.29%) of the mean body weight of each sex. The grouping was done one day prior to initiation of treatment. Body weight of the animals were analyzed statistically for mean body weight to rule out statistical significant differences between groups within each sex.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All the animals were observed once daily for general clinical signs of toxicity. These observations were made approximately at the same time on each day after dose administration. All the animals were observed twice daily for mortality and morbidity.
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All the animals were subjected to detailed clinical examinations on day 1 before treatment and weekly thereafter during treatment. These observations were made outside the home cage and approximately at the same time.
BODY WEIGHT: Yes
- Time schedule for examinations: The main group males were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
The main group females were weighed at receipt, on the first day of dosing, weekly thereafter during pre-mating and until confirmation of mating. All the pregnant animals were weighed on gestation days (GD) 0, 7, 14 and 20 and on lactation days (LD) 1, 4, 7, 13 and 14 (terminal body weight). The non-pregnant animals were weighed weekly once until termination and the terminal body weights were recorded before scheduled sacrifice.
The recovery group animals were weighed at receipt, on the first day of dosing, weekly thereafter and at termination.
FOOD EFFICIENCY:
- Cage wise feed consumption was measured for all main group males and females, once in a week during premating period coinciding with body weight recording.
Cage wise feed consumption was measured for all pregnant animals during gestation day (GD) 0 to 7, 7 to 14 and 14 to 20, during lactation day (LD) 1 to 4, 4 to 7 and
7 to 13 coinciding with body weight recording.
Cage wise feed consumption was measured for all recovery group animals once in a week throughout the experimental period coinciding with body weight recording.
Average feed intake per animal (g/animal/day) was calculated using the amount of feed offered and left over in each cage and the number of rats per cage.
Feed consumption was not measured during following occasions, but offered ad libitum of feed:
- cohabitation period for both sexes of main groups;
- after GD 20 and until parturition for pregnant females;
- from day 20 after confirmation of mating until termination for non-pregnant females.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Ophthalmological examination was carried out for all animals before initiation of treatment i.e. after grouping and randomization (last day of acclimatization). Ophthalmological examination was also carried out at the end of dosing period for all males (shortly prior to scheduled sacrifice, i.e. day 30) and during lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13) and during last week (i.e. day 65) for the recovery group animals.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.16] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples of both males and females were collected on the day of scheduled terminal sacrifice (for main group males after completion of 31 days of dose administration, for main group females on lactation day 14 and for recovery group animals on the day of scheduled sacrifice.
- Animals fasted: Yes
- How many animals: 12 Males and 12 Femles from all the main groups; 5 Males and 5 Females from all the recovery groups.
- Parameters checked in table [No.17] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: Urine was collected from five randomly selected males of each main group and for all recovery animals at termination. The selected animals were placed in urine collection cages overnight and not given access to feed but water was provided ad libitum during their stay in the urine collection cages. The overnight urine volume (mL) collected from these animals were measured.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.18] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Neurological/Functional examination was performed for five males and five females, randomly selected from each group, towards the end of the dosing period for males (shortly prior to scheduled sacrifice, i.e. on day 30) and during the lactation period for females (shortly prior to scheduled sacrifice, i.e. on lactation day 13). Neurological/Functional examination was performed for all recovery group animals towards the end of the recovery period (shortly prior to scheduled sacrifice, i.e.
on day 65.
- Dose groups that were examined: G1/G1R, G2, G3 and G4/G4R.
- Battery of functions tested: sensory activity, grip strength, motor activity and Hindlimb Footsplay.
Thyroid Hormone Estimations: Blood collection for Thyroxine (T4) Level estimation: Blood samples were collected from all the main group animals for measurement of serum T4 levels on the following schedule:
- All dams at termination (lactation day 14).
- All adult males, at termination (after completion of 31 days of treatment).
The assessment of serum T4 levels was performed for adult males. Further assessment of T4 levels in serum samples from the dams was not assessed as there were no treatment-related effects observed in the T4 levels of adult males.
The collected blood samples were centrifuged at 5000 rpm for 10 minutes; the serum was separated and stored at freezing conditions (-80ºC ± 10ºC) till estimation.
The serum samples were estimated for thyroid hormonal levels (Thyroxine - T4) by the ELISA method using commercial assay kits. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- The statistical analysis tests followed for the interpretation of data are as mentioned below:
• Body weight (weekly/gestation/lactation)
• Percent Change in body weight (weekly/gestation/lactation)
• Feed consumption (weekly/gestation/lactation)
• Hematology
• Clinical chemistry
• Urinalysis
• Absolute/relative organ weights
• Functional Observation parameters
• Thyroid hormonal levels
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no clinical signs of toxicity recorded in any of the animals of both sexes from all the tested dose groups throughout the experimental period. However, dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4R animals. This coloration was due to colored nature of the test item but not any adverse signs.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food efficiency
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- other: THyroid hormonal lelves
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
TABLE 1. SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION AND
MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, M & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, M & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, M & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, M & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
M:
Male; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1, F & 0 |
12 |
N (12) |
NAD (12) |
0 (12) |
G2, F & 111 |
12 |
N (12) |
NAD (12) |
0 (12) |
G3, F & 333 |
12 |
N (12) |
NAD (12) |
0 (12) |
G4, F & 1000 |
12 |
N (12) |
NAD (12) |
0 (12) |
F:
Female; N: Normal; NAD: No Abnormality Detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 observation throughout the experiment period till termination in group G3 & G4 animals.
TABLE 1 (Contd…). SUMMARY
OF CLINICAL SIGNS OF TOXICITY, DETAILED CLINICAL EXAMINATION
AND MORTALITY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total No. of Animals |
Clinical Signs of Toxicitya: Observation |
Detailed Clinical Examinationb: Observation |
Mortalityc: No. of Mortalities |
G1R, M & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, M & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
G1R, F & 0 |
5 |
N (5) |
NAD (5) |
0 (5) |
G4R, F & 1000 |
5 |
N (5) |
NAD (5) |
0 (5) |
M:
Male; F: Female; R: Recovery; N: Normal; NAD: No abnormality detected.
a: observed once daily; b: observed once weekly; c: observed twice daily.
Note:Dark purple colored faeces were noted from day 2 throughout the experiment period till termination in group G4R animals.
TABLE 2. SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
|||||
1 |
7 |
14 |
21 |
28 |
|||
G1, M & 0 |
Mean |
400.75 |
421.20 |
438.19 |
446.01 |
458.77 |
|
±SD |
22.07 |
32.34 |
36.49 |
37.08 |
38.53 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
401.74 |
417.26 |
433.41 |
442.75 |
452.56 |
|
±SD |
20.39 |
24.35 |
30.70 |
31.29 |
30.16 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
402.72 |
419.51 |
438.54 |
444.84 |
456.36 |
|
±SD |
19.35 |
23.54 |
30.11 |
27.23 |
24.95 |
||
n |
12 |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
401.99 |
422.76 |
443.74 |
453.94 |
463.38 |
|
±SD |
21.50 |
27.21 |
34.32 |
36.83 |
39.17 |
||
n |
12 |
12 |
12 |
12 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||
1 |
7 |
14 |
21# |
|||
G1, F & 0 |
Mean |
250.88 |
257.35 |
267.91 |
280.34 |
|
±SD |
14.86 |
17.17 |
18.25 |
26.26 |
||
n |
12 |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
251.05 |
256.43 |
266.53 |
272.56 |
|
±SD |
12.78 |
15.62 |
15.30 |
25.98 |
||
n |
12 |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
251.13 |
256.32 |
261.08 |
260.46 |
|
±SD |
13.59 |
14.00 |
15.94 |
17.45 |
||
n |
12 |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
251.24 |
261.46 |
265.51 |
269.05 |
|
±SD |
15.56 |
18.91 |
20.71 |
24.37 |
||
n |
12 |
12 |
12 |
4 |
F: Female; SD: Standard Deviation; n: Number of Animals.
#: The data obtained from females in cohabitation only considered for mean calculations.
The data of day 21 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 2 (Contd…). SUMMARY OF BODY WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Body Weight (g) on Day |
||||||||||
1 |
7 |
14 |
21 |
28 |
35 |
42 |
49 |
56 |
63 |
|||
G1R, M & 0 |
Mean |
395.45 |
407.17 |
422.63 |
436.11 |
448.75 |
458.35 |
473.23 |
489.33 |
502.87 |
514.37 |
|
±SD |
21.72 |
21.10 |
31.29 |
32.45 |
32.78 |
34.62 |
33.67 |
33.58 |
34.92 |
37.99 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
396.36 |
412.35 |
430.15 |
444.31 |
454.98 |
464.82 |
475.04 |
493.68 |
508.20 |
519.69 |
|
±SD |
20.86 |
20.17 |
12.53 |
16.96 |
17.27 |
14.72 |
15.50 |
9.28 |
11.65 |
11.69 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
245.24 |
250.97 |
262.44 |
268.72 |
277.56 |
284.92 |
295.96 |
306.72 |
315.86 |
324.75 |
|
±SD |
10.97 |
10.11 |
13.68 |
15.80 |
15.60 |
15.72 |
19.40 |
19.59 |
17.41 |
15.21 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
245.66 |
248.99 |
264.41 |
270.43 |
278.43 |
286.33 |
298.35 |
308.32 |
318.51 |
327.87 |
|
±SD |
12.82 |
12.43 |
13.84 |
12.16 |
11.19 |
12.10 |
12.79 |
13.72 |
10.97 |
12.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 3. SUMMARY RECORD OF GESTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Gestation Day (GD) |
||||
0 |
7 |
14 |
20 |
||
G1, F & 0 |
Mean |
272.42 |
287.38 |
319.92 |
375.62 |
±SD |
18.33 |
21.41 |
28.89 |
35.87 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
269.81 |
286.87 |
328.45 |
391.71 |
±SD |
11.98 |
12.37 |
15.11 |
22.46 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
264.91 |
282.42 |
317.51 |
369.85 |
±SD |
15.69 |
14.58 |
20.68 |
32.90 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
273.49 |
291.35 |
327.07 |
382.89 |
±SD |
17.37 |
17.37 |
23.26 |
39.30 |
|
n |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis, but presented in individual animal data.
TABLE 4. SUMMARY RECORD OF LACTATION BODY WEIGHT (g)
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Lactation Day (LD) |
||||
1 |
4 |
7 |
13 |
||
G1, F & 0 |
Mean |
294.60 |
300.48 |
308.18 |
323.25 |
±SD |
22.07 |
22.28 |
22.06 |
20.39 |
|
n |
11 |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
306.24 |
309.48 |
314.78 |
330.57 |
±SD |
22.46 |
21.39 |
20.72 |
19.26 |
|
n |
10 |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
293.35 |
297.31 |
304.48 |
319.65 |
±SD |
19.47 |
20.23 |
20.46 |
22.22 |
|
n |
10 |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
303.31 |
306.82 |
313.01 |
325.64 |
±SD |
22.77 |
24.10 |
23.73 |
23.27 |
|
n |
11 |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 5. SUMMARY
OF PERCENT CHANGE IN BODY WEIGHT GAIN (%)
WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
||||
1 to 7 |
1 to 14 |
1 to 21 |
1 to 28 |
|||
G1, M & 0 |
Mean |
5.01 |
9.25 |
11.19 |
14.36 |
|
±SD |
3.10 |
4.96 |
4.86 |
4.98 |
||
n |
12 |
12 |
12 |
12 |
||
G2, M & 111 |
Mean |
3.84 |
7.80 |
10.13 |
12.59 |
|
±SD |
2.04 |
3.09 |
3.48 |
3.20 |
||
n |
12 |
12 |
12 |
12 |
||
G3, M & 333 |
Mean |
4.15 |
8.89 |
10.50 |
13.42 |
|
±SD |
2.15 |
5.14 |
5.14 |
5.61 |
||
n |
12 |
12 |
12 |
12 |
||
G4, M & 1000 |
Mean |
5.12 |
10.29 |
12.82 |
15.16 |
|
±SD |
1.91 |
3.83 |
4.55 |
5.27 |
||
n |
12 |
12 |
12 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 5 (Contd…). SUMMARY OF PERCENTCHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||
1 to 7 |
1 to 14 |
1 to 21# |
|||
G1, F & 0 |
Mean |
2.56 |
6.78 |
10.07 |
|
±SD |
2.21 |
3.23 |
3.01 |
||
n |
12 |
12 |
3 |
||
G2, F & 111 |
Mean |
2.12 |
6.21 |
9.94 |
|
±SD |
2.46 |
4.16 |
1.49 |
||
n |
12 |
12 |
3 |
||
G3, F & 333 |
Mean |
2.08 |
3.94 |
5.98 |
|
±SD |
1.81 |
2.08 |
1.64 |
||
n |
12 |
12 |
4 |
||
G4, F & 1000 |
Mean |
4.05 |
5.61 |
9.37 |
|
±SD |
3.24 |
3.20 |
3.75 |
||
n |
12 |
12 |
4 |
F: Female; SD: Standard Deviation; n: Number of Animals.
#: The data obtained from females in cohabitation only considered for mean calculations. The data of day 1 to 21 body weight was not subjected to statistical analysis due to uneven number of variables.
TABLE 5 (Contd…). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) WITH RESPECT TO DAY1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Percent Change in Body Weight (%) during Day |
|||||||||
1 to 7 |
1 to 14 |
1 to 21 |
1 to 28 |
1 to 35 |
1 to 42 |
1 to 49 |
1 to 56 |
1 to 63 |
|||
G1R, M & 0 |
Mean |
2.98 |
6.83 |
10.25 |
13.47 |
15.92 |
19.69 |
23.73 |
27.13 |
30.00 |
|
±SD |
0.92 |
4.09 |
4.67 |
5.29 |
6.27 |
5.81 |
4.88 |
4.25 |
4.30 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, M & 1000 |
Mean |
4.06 |
8.66 |
12.20 |
14.91 |
17.44 |
20.09 |
24.77 |
28.45 |
31.32 |
|
±SD |
1.73 |
3.60 |
3.33 |
3.84 |
4.90 |
6.78 |
5.51 |
6.10 |
5.14 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G1R, F & 0 |
Mean |
2.35 |
7.00 |
9.55 |
13.20 |
16.19 |
20.62 |
25.02 |
28.77 |
32.44 |
|
±SD |
0.72 |
2.36 |
3.15 |
4.61 |
4.45 |
4.14 |
4.54 |
3.55 |
3.44 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||
G4R, F & 1000 |
Mean |
1.37 |
7.66 |
10.20 |
13.45 |
16.65 |
21.52 |
25.60 |
29.78 |
33.57 |
|
±SD |
1.07 |
2.71 |
4.80 |
4.07 |
3.73 |
3.02 |
4.10 |
3.75 |
3.31 |
||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 6. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Gestation Day (GD) |
|||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
5.46 |
11.22 |
17.44 |
±SD |
1.77 |
2.82 |
4.18 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
6.35 |
14.52 |
19.23 |
±SD |
2.12 |
3.20 |
3.16 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
6.67 |
12.40 |
16.35 |
±SD |
1.92 |
3.55 |
3.43 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
6.56 |
12.23 |
16.88 |
±SD |
1.60 |
3.35 |
4.81 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis, but presented in individual animal data.
TABLE 7. SUMMARY RECORD OF PERCENT CHANGE IN BODY WEIGHT GAIN (%) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight Gain (%) during Lactation Day (LD) |
|||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
2.01 |
2.58 |
4.96 |
±SD |
0.96 |
0.73 |
1.51 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
1.08 |
1.74 |
5.07 |
±SD |
0.86 |
0.95 |
1.60 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
1.35 |
2.42 |
4.98 |
±SD |
0.95 |
1.29 |
1.32 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
1.14 |
2.04 |
4.06 |
±SD |
1.00 |
0.93 |
0.83 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 8. SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/animal/day) during Pre-mating Period |
||
Week 1 |
Week 2 |
||
G1, M & 0 |
Mean |
21.31 |
24.01 |
±SD |
2.38 |
1.81 |
|
n |
12 (6) |
12 (6) |
|
G2, M & 111 |
Mean |
21.39 |
23.12 |
±SD |
1.76 |
0.75 |
|
n |
12 (6) |
12 (6) |
|
G3, M & 333 |
Mean |
22.25 |
23.93 |
±SD |
2.39 |
1.85 |
|
n |
12 (6) |
12 (6) |
|
G4, M & 1000 |
Mean |
22.28 |
24.17 |
±SD |
1.23 |
0.67 |
|
n |
12 (6) |
12 (6) |
M: Male; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Feed Consumption (g/animal/day) during Pre-mating Period |
||
Week 1 |
Week 2 |
||
G1, F & 0 |
Mean |
18.14 |
19.17 |
±SD |
1.56 |
1.22 |
|
n |
12 (6) |
12 (6) |
|
G2, F & 111 |
Mean |
17.79 |
20.11 |
±SD |
1.85 |
1.70 |
|
n |
12 (6) |
12 (6) |
|
G3, F & 333 |
Mean |
18.26 |
19.22 |
±SD |
1.99 |
1.31 |
|
n |
12 (6) |
12 (6) |
|
G4, F & 1000 |
Mean |
18.43 |
20.07 |
±SD |
2.28 |
1.22 |
|
n |
12 (6) |
12 (6) |
F: Female; SD: Standard Deviation; n: Number of Animals (Number of cages).
TABLE 8 (Contd…). SUMMARY OF FEED CONSUMPTION (g/animal/day) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) |
||||||||
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
Week 7 |
Week 8 |
Week 9 |
||
G1R, M & 0 |
Mean |
23.52 |
24.34 |
25.11 |
26.35 |
27.86 |
29.05 |
30.75 |
31.83 |
32.47 |
±SD |
3.71 |
1.67 |
1.55 |
1.27 |
0.97 |
1.11 |
0.47 |
3.66 |
3.01 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, M & 1000 |
Mean |
22.84 |
23.75 |
24.26 |
27.17 |
28.86 |
30.05 |
31.07 |
32.19 |
33.03 |
±SD |
0.77 |
1.04 |
1.34 |
2.09 |
2.61 |
2.18 |
2.12 |
1.59 |
1.67 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G1R, F & 0 |
Mean |
17.44 |
18.36 |
19.45 |
10.21 |
23.17 |
24.20 |
25.35 |
26.19 |
27.04 |
±SD |
1.79 |
0.40 |
0.40 |
9.72 |
0.99 |
0.82 |
0.62 |
0.41 |
0.99 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
|
G4R, F & 1000 |
Mean |
17.21 |
19.05 |
20.42 |
11.29 |
24.18 |
25.37 |
26.19 |
27.14 |
27.89 |
±SD |
0.69 |
1.77 |
0.91 |
10.38 |
0.03 |
0.80 |
0.84 |
0.69 |
0.68 |
|
n |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
5 (3) |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals(Number of cages).
TABLE 9. SUMMARY RECORD OF FEED CONSUMPTION (g/animal/day) DURING GESTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) during Gestation Day (GD) |
||
0 to 7 |
7 to 14 |
14 to 20 |
||
G1, F & 0 |
Mean |
19.02 |
21.07 |
25.81 |
SD |
0.70 |
1.95 |
1.63 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
19.23 |
22.20 |
26.84 |
SD |
0.88 |
1.81 |
1.78 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
19.00 |
21.49 |
26.11 |
SD |
0.74 |
1.39 |
1.26 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
19.43 |
22.01 |
26.67 |
SD |
0.58 |
1.70 |
1.97 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
Note: Excluded the data of non-pregnant females for mean calculations and statistical analysis but presented in individual animal data.
TABLE 10. SUMMARY RECORD OF FEED CONSUMTION (g/animal/day) DURING LACTATION PERIOD
Group, Sex & Dose (mg/kg body weight/day) |
|
Feed Consumption (g/animal/day) during Lactation Day (LD) |
||
1 to 4 |
4 to 7 |
7 to 13 |
||
G1, F & 0 |
Mean |
25.21 |
35.80 |
40.88 |
SD |
1.20 |
7.26 |
1.43 |
|
n |
11 |
11 |
11 |
|
G2, F & 111 |
Mean |
24.58 |
32.72 |
41.09 |
SD |
1.34 |
0.99 |
0.98 |
|
n |
10 |
10 |
10 |
|
G3, F & 333 |
Mean |
25.11 |
32.75 |
40.54 |
SD |
1.42 |
1.16 |
0.94 |
|
n |
10 |
10 |
10 |
|
G4, F & 1000 |
Mean |
23.94 |
33.14 |
39.84 |
SD |
5.99 |
1.28 |
1.03 |
|
n |
11 |
11 |
11 |
F: Female; SD: Standard Deviation; n: Number of Dams.
TABLE 11. SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day -1 (Grouping and randomization) |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 30 |
||||||||
Group, Sex & Dose weight/day) → |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
M: Male; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Pregnant/Littered females: Lactation day 13; Non-pregnant females: (Experimental day 39 to 52) |
||||||||
Group, Sex & Dose weight/day) → |
G1, F & 0 |
G2, F & 111 |
G3, F & 333 |
G4, F & 1000 |
||||
Number of Animals→ |
12 |
12 |
12 |
12 |
||||
Observations↓ |
||||||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
N |
N |
N |
N |
F: Female; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, M & 0 |
G4R, M & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
M: Male; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 11 (Contd…). SUMMARY OF OPHTHALMOLOGICAL EXAMINATION RECORD
Day 65 |
||||
Group, Sex & Dose weight/day) → |
G1R, F & 0 |
G4R, F & 1000 |
||
Number of Animals→ |
5 |
5 |
||
Observations↓ |
||||
Eye→ Region↓ |
LE |
RE |
LE |
RE |
Eye Lids |
N |
N |
N |
N |
Cornea |
N |
N |
N |
N |
Iris |
N |
N |
N |
N |
Aqueous Humour |
N |
N |
N |
N |
Lens |
N |
N |
N |
N |
Vitreous Humour |
N |
N |
N |
N |
Retina/Optic disc |
N |
N |
N |
N |
Other findings: |
N |
N |
N |
N |
F: Female; R: Recovery; N: Normal; LE: Left Eye; RE: Right Eye.
TABLE 12. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Day 30 |
||||||
Parameters↓ |
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.4 |
4.8 |
4.8 |
4.8 |
|
±SD |
1.1 |
0.8 |
0.8 |
0.8 |
||
Number of urine pools |
Mean |
3.4 |
3.8 |
3.8 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.8 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.4 |
3.2 |
3.4 |
3.2 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.1 |
98.4 |
|
±SD |
0.5 |
0.4 |
0.3 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Home Cage Observations |
||||||
Home cage posture |
1 |
1 |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
1 |
1 |
||
Vocalization |
1 |
1 |
1 |
1 |
||
Palpebral closure |
1 |
1 |
1 |
1 |
||
Handling Observations |
||||||
Ease of removal from the cage |
2 |
2 |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
1 |
1 |
|
Nose |
1 |
1 |
1 |
1 |
||
Mouth |
1 |
1 |
1 |
1 |
||
Lacrimation |
1 |
1 |
1 |
1 |
||
Salivation |
1 |
1 |
1 |
1 |
||
Fur appearance |
1 |
1 |
1 |
1 |
||
Piloerection |
1 |
1 |
1 |
1 |
||
Eye prominence |
1 |
1 |
1 |
1 |
||
Muscle tone |
1 |
1 |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Lactation Day 13 |
||||||
Parameters↓ |
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
|
Dose (mg/kg body weight/day) |
0 |
111 |
333 |
1000 |
||
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Open Field Observations |
||||||
Mobility |
1 |
1 |
1 |
1 |
||
Gait |
1 |
1 |
1 |
1 |
||
Arousal |
3 |
3 |
3 |
3 |
||
Number of rearing |
Mean |
4.8 |
4.8 |
4.8 |
4.8 |
|
±SD |
0.8 |
0.8 |
0.8 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
2.8 |
3.2 |
|
±SD |
0.9 |
0.7 |
0.8 |
0.4 |
||
Clonic involuntary movement |
1 |
1 |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
2.6 |
3.0 |
|
±SD |
0.4 |
0.8 |
0.5 |
0.7 |
||
Sensory Observations |
||||||
Approach response |
2 |
2 |
2 |
2 |
||
Auditory response |
2 |
2 |
2 |
2 |
||
Touch response |
2 |
2 |
2 |
2 |
||
Pupil reflex |
2 |
2 |
2 |
2 |
||
Tail pinch response |
2 |
2 |
2 |
2 |
||
Righting reflex |
1 |
1 |
1 |
1 |
||
Physiological Observation |
||||||
Body temperature (°F) |
Mean |
98.4 |
98.4 |
98.8 |
98.7 |
|
±SD |
0.6 |
0.5 |
0.5 |
0.8 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & M |
G4R & M |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.4 |
|
±SD |
1.0 |
1.1 |
||
Numbers of urine pools |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Number of defecations |
Mean |
3.6 |
3.4 |
|
±SD |
0.5 |
0.5 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.6 |
3.2 |
|
±SD |
0.5 |
0.4 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.5 |
98.6 |
|
±SD |
0.5 |
0.5 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Home Cage Observations |
||||
Home cage posture |
1 |
1 |
||
Respiratory pattern |
1 |
1 |
||
Clonic involuntary movements |
1 |
1 |
||
Tonic involuntary movements |
1 |
1 |
||
Vocalization |
1 |
1 |
||
Palpebral closure |
1 |
1 |
||
Handling Observations |
||||
Ease of removal from the cage |
2 |
2 |
||
Ease of handling animal in hand |
2 |
2 |
||
Red or crusty deposits |
Eyes |
1 |
1 |
|
Nose |
1 |
1 |
||
Mouth |
1 |
1 |
||
Lacrimation |
1 |
1 |
||
Salivation |
1 |
1 |
||
Fur appearance |
1 |
1 |
||
Piloerection |
1 |
1 |
||
Eye prominence |
1 |
1 |
||
Muscle tone |
1 |
1 |
||
Home Cage Observations:Home cage posture - 1=Normal; Respiratory pattern - 1=Normal; Clonic involuntary movements - 1=None; Tonic involuntary movements - 1=None; Vocalization - 1=None; Palpebral closure - 1=Normal;Handling Observations:Ease of removal from the cage - 2=Normal; Ease of handling animal in hand - 2=Normal; Red or crusty deposits - 1=Absent; Lacrimation - 1=None; Salivation- 1=None; Fur appearance - 1=Normal; Piloerection - 1=None; Eye Prominence - 1=Normal; Muscle tone - 1=Normal |
TABLE 12 (Contd…). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)
Day 65 |
||||
Parameters↓ |
Group & Sex |
G1R & F |
G4R & F |
|
Dose (mg/kg body weight/day) |
0 |
1000 |
||
Number of Animals |
5 |
5 |
||
Open Field Observations |
||||
Mobility |
1 |
1 |
||
Gait |
1 |
1 |
||
Arousal |
3 |
3 |
||
Number of rearing |
Mean |
5.0 |
4.8 |
|
±SD |
1.0 |
0.8 |
||
Numbers of urine pools |
Mean |
3.6 |
3.8 |
|
±SD |
0.5 |
0.8 |
||
Number of defecations |
Mean |
3.4 |
3.0 |
|
±SD |
0.9 |
0.7 |
||
Clonic involuntary movement |
1 |
1 |
||
Tonic involuntary movement |
1 |
1 |
||
Stereotype behaviour |
1 |
1 |
||
Number of grooming |
Mean |
3.2 |
3.2 |
|
±SD |
0.4 |
0.8 |
||
Sensory Observations |
||||
Approach response |
2 |
2 |
||
Auditory response |
2 |
2 |
||
Touch response |
2 |
2 |
||
Pupil reflex |
2 |
2 |
||
Tail pinch response |
2 |
2 |
||
Righting reflex |
1 |
1 |
||
Physiological Observation |
||||
Body temperature (°F) |
Mean |
98.4 |
98.3 |
|
±SD |
0.5 |
0.7 |
||
Open Field Observations: Mobility- 1=Normal;Gait- 1=Normal;Arousal- 3=Normal;Clonic involuntary movement- 1=None;Tonic involuntary movement -1=None;Stereotype behaviour -1=Absent;Sensory Observations:Approach response- 2=Normal;Auditory response- 2=Normal;Touch response -2=Normal;Pupil reflex- 2=Normal;Tail pinch response- 2=Normal;Righting reflex- 1=Present |
TABLE 13. SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, M & 0 |
Mean |
1911.4 |
±SD |
108.9 |
|
n |
5 |
|
G2, M & 111 |
Mean |
1961.8 |
±SD |
138.9 |
|
n |
5 |
|
G3, M & 333 |
Mean |
1954.2 |
±SD |
126.1 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
1931.4 |
±SD |
104.0 |
|
n |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1, F & 0 |
Mean |
1923.4 |
±SD |
102.7 |
|
n |
5 |
|
G2, F & 111 |
Mean |
1941.4 |
±SD |
125.1 |
|
n |
5 |
|
G3, F & 333 |
Mean |
1989.0 |
±SD |
103.1 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
1973.2 |
±SD |
84.7 |
|
n |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 13 (Contd…). SUMMARY OF LOCOMOTOR ACTIVITY / MOVEMENT COUNTS RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Movement Counts (no.) |
|
G1R, M & 0 |
Mean |
2014.2 |
±SD |
210.7 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
1980.6 |
±SD |
197.8 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
1943.4 |
±SD |
87.8 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
1956.2 |
±SD |
91.6 |
|
n |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 14. SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 30 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, M & 0 |
Mean |
1.529 |
0.510 |
±SD |
0.023 |
0.025 |
|
n |
5 |
5 |
|
G2, M & 111 |
Mean |
1.501 |
0.539 |
±SD |
0.020 |
0.021 |
|
n |
5 |
5 |
|
G3, M & 333 |
Mean |
1.521 |
0.552* |
±SD |
0.048 |
0.008 |
|
n |
5 |
5 |
|
G4, M & 1000 |
Mean |
1.539 |
0.544* |
±SD |
0.040 |
0.015 |
|
n |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Lactation Day 13 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1, F & 0 |
Mean |
1.496 |
0.508 |
±SD |
0.009 |
0.008 |
|
n |
5 |
5 |
|
G2, F & 111 |
Mean |
1.493 |
0.488 |
±SD |
0.010 |
0.015 |
|
n |
5 |
5 |
|
G3, F & 333 |
Mean |
1.496 |
0.493 |
±SD |
0.009 |
0.021 |
|
n |
5 |
5 |
|
G4, F & 1000 |
Mean |
1.498 |
0.499 |
±SD |
0.011 |
0.020 |
|
n |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 14 (Contd…). SUMMARY OF AVERAGE GRIP STRENGTH (kgf) MEASUREMENT RECORD
Day 65 |
|||
Group, Sex & Dose (mg/kg body weight/day) |
Grip Strength (kgf) |
||
Forelimb |
Hindlimb |
||
G1R, M & 0 |
Mean |
1.515 |
0.534 |
±SD |
0.020 |
0.035 |
|
n |
5 |
5 |
|
G4R, M & 1000 |
Mean |
1.528 |
0.533 |
±SD |
0.029 |
0.009 |
|
n |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.516 |
0.499 |
±SD |
0.031 |
0.021 |
|
n |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.503 |
0.481 |
±SD |
0.012 |
0.012 |
|
n |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 15. SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 30 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, M & 0 |
Mean |
9.0 |
±SD |
1.0 |
|
n |
5 |
|
G2, M & 111 |
Mean |
8.8 |
±SD |
1.3 |
|
n |
5 |
|
G3, M & 333 |
Mean |
9.3 |
±SD |
0.6 |
|
n |
5 |
|
G4, M & 1000 |
Mean |
8.6 |
±SD |
0.6 |
|
n |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Lactation Day 13 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1, F & 0 |
Mean |
8.0 |
±SD |
0.5 |
|
n |
5 |
|
G2, F & 111 |
Mean |
7.9 |
±SD |
0.5 |
|
n |
5 |
|
G3, F & 333 |
Mean |
8.1 |
±SD |
1.0 |
|
n |
5 |
|
G4, F & 1000 |
Mean |
8.5 |
±SD |
0.9 |
|
n |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 15 (Contd…). SUMMARY OF AVERAGE HINDLIMB FOOT SPLAY (cm) RECORD
Day 65 |
||
Group, Sex & Dose (mg/kg body weight/day) |
Hindlimb Foot Splay (cm) |
|
G1R, M & 0 |
Mean |
8.6 |
±SD |
0.3 |
|
n |
5 |
|
G4R, M & 1000 |
Mean |
9.0 |
±SD |
0.4 |
|
n |
5 |
|
G1R, F & 0 |
Mean |
8.4 |
±SD |
0.4 |
|
n |
5 |
|
G4R, F & 1000 |
Mean |
7.6* |
±SD |
0.2 |
|
n |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, M & 0 |
Mean |
8.26 |
9.64 |
17.56 |
52.80 |
55.00 |
18.30 |
33.26 |
776.40 |
7.72 |
±SD |
1.95 |
1.09 |
1.34 |
4.49 |
3.09 |
1.14 |
0.53 |
330.86 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
9.68 |
9.37 |
16.82 |
51.32 |
54.72 |
17.94 |
32.80 |
1135.20 |
7.46 |
±SD |
2.59 |
0.15 |
0.33 |
0.89 |
1.12 |
0.29 |
0.58 |
184.30 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
8.67 |
9.40 |
16.58 |
50.78 |
54.12 |
17.64 |
32.62 |
962.60 |
7.72 |
±SD |
3.67 |
0.62 |
0.87 |
1.91 |
1.72 |
0.59 |
0.70 |
256.00 |
0.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
8.14 |
9.35 |
16.88 |
52.02 |
55.74 |
18.06 |
32.46 |
1017.60 |
7.50 |
±SD |
2.42 |
0.54 |
0.55 |
1.58 |
2.71 |
0.74 |
0.53 |
93.02 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, M & 0 |
Mean |
2.25 |
23.48 |
72.02 |
2.38 |
0.44 |
0.80 |
±SD |
1.24 |
9.09 |
9.80 |
1.15 |
0.17 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
1.87 |
19.66 |
75.74 |
2.28 |
1.04 |
0.54 |
±SD |
0.64 |
3.44 |
3.55 |
0.74 |
0.59 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
1.87 |
21.98 |
70.58 |
2.40 |
1.04 |
0.62 |
±SD |
0.60 |
5.35 |
7.57 |
2.37 |
0.34 |
0.61 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
2.01 |
20.86 |
75.78 |
1.42 |
0.72 |
0.54 |
±SD |
0.79 |
3.34 |
2.92 |
0.23 |
0.25 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, M & 0 |
Mean |
212.96 |
1.83 |
6.07 |
0.19 |
0.04 |
0.07 |
15.54 |
22.26 |
±SD |
101.87 |
0.42 |
2.01 |
0.08 |
0.02 |
0.06 |
0.78 |
6.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
174.50 |
1.91 |
7.33 |
0.23 |
0.10* |
0.05 |
15.72 |
25.28 |
±SD |
56.93 |
0.64 |
1.96 |
0.10 |
0.04 |
0.02 |
1.03 |
1.56 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
175.20 |
1.80 |
5.98 |
0.27 |
0.09* |
0.07 |
16.72 |
24.30 |
±SD |
59.25 |
0.52 |
1.97 |
0.39 |
0.03 |
0.11 |
1.49 |
1.59 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
184.78 |
1.70 |
6.17 |
0.11 |
0.06 |
0.04 |
15.98 |
26.78 |
±SD |
67.09 |
0.55 |
1.89 |
0.04 |
0.02 |
0.02 |
0.89 |
1.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1, F & 0 |
Mean |
10.56 |
7.85 |
15.74 |
46.26 |
59.02 |
20.04 |
34.04 |
752.60 |
6.02 |
±SD |
3.78 |
0.45 |
0.65 |
3.16 |
4.16 |
1.08 |
0.91 |
361.58 |
0.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
11.38 |
7.41 |
14.66 |
44.60 |
60.26 |
19.74 |
32.82 |
1130.00 |
6.72 |
±SD |
3.45 |
0.68 |
1.58 |
3.35 |
1.37 |
0.42 |
1.34 |
672.21 |
0.54 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
9.62 |
7.95 |
15.56 |
46.34 |
58.34 |
19.60 |
33.60 |
1030.20 |
6.42 |
±SD |
3.95 |
0.28 |
0.72 |
2.05 |
3.12 |
0.81 |
1.07 |
104.22 |
0.57 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
12.38 |
7.39 |
14.68 |
43.46 |
59.06 |
19.98 |
33.80 |
1003.00 |
6.92 |
±SD |
3.58 |
0.76 |
0.89 |
2.75 |
3.76 |
1.58 |
0.63 |
227.17 |
0.68 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1, F & 0 |
Mean |
2.28 |
32.72 |
60.66 |
3.68 |
1.46 |
0.60 |
±SD |
0.87 |
15.77 |
16.88 |
1.06 |
0.98 |
0.23 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
4.52 |
30.00 |
62.56 |
4.60 |
1.18 |
0.42 |
±SD |
4.56 |
11.00 |
11.24 |
1.35 |
0.63 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
1.49 |
25.26 |
66.92 |
4.46 |
1.22 |
0.80 |
±SD |
0.67 |
9.73 |
12.89 |
4.23 |
0.33 |
1.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.16 |
37.00 |
57.76 |
3.10 |
0.88 |
0.28 |
±SD |
2.72 |
20.56 |
20.80 |
0.97 |
0.47 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1, F & 0 |
Mean |
177.36 |
3.64 |
6.21 |
0.40 |
0.15 |
0.06 |
17.60 |
23.34 |
±SD |
60.94 |
2.11 |
2.30 |
0.19 |
0.09 |
0.03 |
1.02 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
313.86 |
3.59 |
6.91 |
0.56 |
0.12 |
0.05 |
22.06 |
27.48 |
±SD |
276.22 |
2.17 |
1.72 |
0.29 |
0.04 |
0.02 |
8.41 |
10.47 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
117.60 |
2.64 |
6.29 |
0.39 |
0.12 |
0.06 |
16.88 |
22.08 |
±SD |
50.69 |
2.06 |
2.26 |
0.31 |
0.07 |
0.08 |
3.84 |
7.81 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
291.70 |
4.81 |
6.94 |
0.38 |
0.10 |
0.04 |
15.66 |
19.92 |
±SD |
145.98 |
3.66 |
3.06 |
0.17 |
0.03 |
0.02 |
3.85 |
5.41 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Haemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Haemoglobin |
Mean Corpuscular Haemoglobin Concentration |
Platelet Count |
Mean Platelet Volume |
|
(WBC) |
(RBC) |
(HGB) |
(HCT) |
(MCV) |
(MCH) |
(MCHC) |
(PLT) |
(MPV) |
||
(103cells/µL) |
(106cells/µL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(103cells/µL) |
(fL) |
||
G1R, M & 0 |
Mean |
9.13 |
9.21 |
16.04 |
48.76 |
52.94 |
17.42 |
32.92 |
894.80 |
6.50 |
±SD |
0.78 |
0.14 |
0.43 |
1.79 |
1.78 |
0.39 |
0.42 |
134.10 |
0.31 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
9.55 |
9.14 |
15.80 |
48.54 |
53.08 |
17.30 |
32.62 |
1071.80 |
6.42 |
±SD |
1.05 |
0.32 |
0.65 |
2.25 |
0.91 |
0.30 |
0.57 |
268.87 |
0.37 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
6.97 |
7.65 |
14.26 |
42.16 |
55.20 |
18.64 |
33.78 |
873.60 |
6.32 |
±SD |
2.14 |
0.43 |
0.65 |
2.05 |
1.99 |
0.70 |
0.29 |
80.79 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
7.59 |
7.73 |
14.32 |
42.78 |
55.34 |
18.48 |
33.46 |
739.60 |
6.52 |
±SD |
3.51 |
0.22 |
0.57 |
1.63 |
2.15 |
0.70 |
0.25 |
253.21 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
|
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
||
G1R, M & 0 |
Mean |
1.63 |
25.28 |
69.00 |
1.76 |
2.30 |
0.88 |
±SD |
0.26 |
6.62 |
7.82 |
0.49 |
0.89 |
0.26 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
2.03 |
21.70 |
73.32 |
1.48 |
2.02 |
0.60 |
±SD |
0.50 |
5.52 |
5.80 |
0.37 |
0.36 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
1.84 |
26.12 |
68.68 |
2.30 |
1.34 |
0.68 |
±SD |
0.36 |
9.06 |
8.57 |
1.19 |
0.45 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
2.48* |
29.02 |
64.16 |
2.40 |
2.86* |
0.64 |
±SD |
0.39 |
7.89 |
6.96 |
0.87 |
1.30 |
0.13 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 16 (Contd…). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Absolute Reticulocyte Count |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
||
(109cells/L) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
||
G1R, M & 0 |
Mean |
150.40 |
2.27 |
6.35 |
0.16 |
0.21 |
0.08 |
16.00 |
21.56 |
±SD |
23.36 |
0.40 |
1.23 |
0.04 |
0.07 |
0.02 |
2.04 |
2.05 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
186.92 |
2.06 |
7.02 |
0.14 |
0.19 |
0.05 |
15.50 |
22.48 |
±SD |
52.68 |
0.53 |
1.09 |
0.04 |
0.04 |
0.03 |
1.17 |
3.12 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
140.08 |
1.78 |
4.83 |
0.15 |
0.09 |
0.05 |
14.98 |
24.56 |
±SD |
23.05 |
0.73 |
1.73 |
0.05 |
0.02 |
0.01 |
0.53 |
1.98 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
192.10* |
2.06 |
4.98 |
0.17 |
0.25 |
0.05 |
15.92 |
19.34* |
±SD |
30.17 |
0.60 |
2.77 |
0.07 |
0.24 |
0.02 |
1.17 |
2.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17. SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, M & 0 |
Mean |
126.60 |
30.52 |
0.58 |
51.60 |
25.60 |
7.74 |
3.47 |
±SD |
15.47 |
2.56 |
0.03 |
3.36 |
2.30 |
0.26 |
0.19 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
123.60 |
33.30 |
0.57 |
60.60 |
30.40 |
7.24* |
3.55 |
±SD |
5.55 |
3.91 |
0.04 |
4.83 |
6.07 |
0.33 |
0.15 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
122.60 |
33.78 |
0.60 |
58.00 |
29.40 |
7.44 |
3.65 |
±SD |
12.92 |
2.83 |
0.03 |
6.71 |
7.73 |
0.22 |
0.29 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
131.00 |
36.04 |
0.59 |
56.00 |
27.00 |
7.58 |
3.68 |
±SD |
19.79 |
4.26 |
0.02 |
9.57 |
6.16 |
0.29 |
0.24 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, M & 0 |
Mean |
61.20 |
111.20 |
125.80 |
0.05 |
9.36 |
6.48 |
±SD |
16.93 |
12.34 |
21.11 |
0.01 |
0.11 |
0.58 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
47.40 |
93.20 |
120.00 |
0.06 |
9.64 |
6.54 |
±SD |
8.96 |
13.46 |
31.92 |
0.03 |
0.47 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
40.00 |
81.60* |
127.20 |
0.06 |
10.40* |
6.82 |
±SD |
5.96 |
12.30 |
38.01 |
0.03 |
1.05 |
0.62 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
52.20 |
91.80 |
114.80 |
0.06 |
9.94 |
6.62 |
±SD |
24.52 |
18.69 |
28.70 |
0.02 |
0.30 |
0.49 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected) ; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, M & 0 |
Mean |
4.27 |
0.82 |
14.24 |
141.64 |
3.96 |
104.10 |
±SD |
0.30 |
0.09 |
1.19 |
0.94 |
0.25 |
2.51 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
3.69* |
0.97 |
15.54 |
142.16 |
3.71 |
105.38 |
±SD |
0.38 |
0.12 |
1.83 |
0.53 |
0.15 |
1.40 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
3.79* |
0.97 |
15.77 |
142.44 |
3.86 |
105.78 |
±SD |
0.12 |
0.10 |
1.32 |
0.93 |
0.36 |
1.73 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
3.90 |
0.95 |
16.82 |
142.76 |
3.85 |
106.40 |
±SD |
0.29 |
0.11 |
1.99 |
0.66 |
0.09 |
0.86 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals (randomly selected); *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1, F & 0 |
Mean |
102.20 |
48.68 |
0.54 |
76.60 |
78.60 |
7.32 |
3.63 |
±SD |
26.22 |
8.11 |
0.05 |
22.67 |
26.83 |
1.08 |
0.67 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
121.20 |
51.14 |
0.52 |
67.80 |
59.40 |
7.34 |
3.41 |
±SD |
29.64 |
13.28 |
0.03 |
17.67 |
23.65 |
0.75 |
0.30 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
103.80 |
44.78 |
0.57 |
75.60 |
43.20 |
7.56 |
3.58 |
±SD |
13.81 |
19.81 |
0.04 |
14.91 |
21.48 |
0.29 |
0.32 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
114.60 |
51.66 |
0.57 |
75.80 |
105.20 |
7.76 |
3.70 |
±SD |
16.44 |
16.16 |
0.07 |
20.44 |
68.28 |
0.58 |
0.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine |
Aspartate |
Alkaline |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1, F & 0 |
Mean |
84.60 |
119.40 |
164.40 |
0.03 |
10.06 |
5.92 |
±SD |
14.43 |
14.31 |
75.62 |
0.04 |
1.06 |
0.95 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
113.80 |
143.80 |
420.00 |
0.02 |
9.42 |
5.50 |
±SD |
66.08 |
71.78 |
367.29 |
0.02 |
0.64 |
1.64 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
96.20 |
99.40 |
305.80 |
0.06 |
10.04 |
6.06 |
±SD |
82.35 |
16.01 |
412.83 |
0.02 |
0.85 |
1.93 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
88.60 |
101.80 |
212.40 |
0.03 |
10.38 |
6.38 |
±SD |
46.69 |
22.65 |
81.17 |
0.04 |
0.91 |
3.11 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1, F & 0 |
Mean |
3.69 |
0.98 |
22.72 |
143.04 |
4.02 |
106.18 |
±SD |
0.50 |
0.11 |
3.79 |
1.34 |
0.81 |
2.96 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G2, F & 111 |
Mean |
3.93 |
0.88 |
23.87 |
142.18 |
3.57 |
107.22 |
±SD |
0.66 |
0.14 |
6.20 |
1.47 |
0.28 |
3.01 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G3, F & 333 |
Mean |
3.98 |
0.91 |
20.90 |
142.36 |
3.60 |
107.94 |
±SD |
0.40 |
0.16 |
9.25 |
1.61 |
0.33 |
2.63 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4, F & 1000 |
Mean |
4.06 |
0.92 |
24.11 |
142.62 |
3.86 |
107.06 |
±SD |
0.50 |
0.09 |
7.55 |
1.62 |
0.40 |
3.20 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals (randomly selected).
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Protein |
Albumin |
|
(GLU) |
- |
(CRE) |
(CHO) |
(TRI) |
(TPR) |
(ALB) |
||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
||
G1R, M & 0 |
Mean |
99.80 |
27.36 |
0.55 |
59.60 |
23.00 |
6.98 |
3.10 |
±SD |
6.53 |
3.92 |
0.02 |
16.21 |
5.52 |
0.26 |
0.07 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
99.40 |
25.74 |
0.56 |
68.80 |
31.60 |
7.12 |
3.05 |
±SD |
10.53 |
1.19 |
0.03 |
8.76 |
10.78 |
0.11 |
0.04 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
120.40 |
35.68 |
0.61 |
106.40 |
49.60 |
8.44 |
4.10 |
±SD |
7.16 |
7.57 |
0.02 |
17.07 |
34.09 |
0.56 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
104.00* |
31.42 |
0.59 |
89.20 |
41.60 |
8.04 |
3.70 |
±SD |
13.49 |
2.25 |
0.01 |
16.98 |
11.87 |
0.42 |
0.44 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alanine aminotransferase |
Aspartate aminotransferase |
Alkaline phosphatase |
Total Bilirubin |
Calcium |
Phosphorous |
|
(ALT) |
(AST) |
(ALP) |
(BIT) |
(CAL) |
(PHO) |
||
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
||
G1R, M & 0 |
Mean |
52.00 |
101.80 |
99.00 |
0.02 |
10.42 |
5.72 |
±SD |
40.34 |
53.17 |
23.40 |
0.02 |
0.37 |
0.34 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
42.60 |
98.40 |
105.20 |
0.02 |
10.02 |
5.26 |
±SD |
9.86 |
18.49 |
29.84 |
0.01 |
0.15 |
0.50 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
54.00 |
94.00 |
70.80 |
0.02 |
11.20 |
4.20 |
±SD |
28.82 |
36.89 |
40.92 |
0.02 |
0.45 |
0.38 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
53.80 |
103.20 |
69.00 |
0.04 |
10.90 |
4.42 |
±SD |
21.53 |
39.30 |
60.10 |
0.02 |
0.37 |
0.18 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals.
TABLE 17 (Contd…). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Globulin |
Albumin/ Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||
(g/dL) |
- |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
||
G1R, M & 0 |
Mean |
3.88 |
0.80 |
12.77 |
142.82 |
3.56 |
105.48 |
±SD |
0.27 |
0.06 |
1.83 |
0.36 |
0.41 |
0.92 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
4.07 |
0.75 |
12.01 |
143.16 |
3.59 |
108.06* |
±SD |
0.15 |
0.04 |
0.56 |
0.68 |
0.41 |
1.65 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G1R, F & 0 |
Mean |
4.34 |
0.95 |
16.65 |
142.62 |
3.45 |
105.76 |
±SD |
0.42 |
0.08 |
3.53 |
0.94 |
0.17 |
1.52 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
4.34 |
0.85 |
14.66 |
142.26 |
3.62 |
106.40 |
±SD |
0.21 |
0.12 |
1.05 |
1.41 |
0.48 |
2.88 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 18. SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1, M & 0 |
G2, M & 111 |
G3, M & 333 |
G4, M & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
5 |
5 |
5 |
5 |
Appearance |
Clear |
5 |
5 |
5 |
5 |
|
Volume (mL) |
Mean |
10.6 |
10.2 |
11.0 |
11.4 |
|
±SD |
0.7 |
1.4 |
0.8 |
0.4 |
||
Chemical Examination |
pH |
Mean |
7.5 |
7.4 |
7.4 |
7.5 |
±SD |
0.0 |
0.4 |
0.5 |
0.0 |
||
Specific Gravity |
Mean |
1.008 |
1.011 |
1.009 |
1.009 |
|
±SD |
0.003 |
0.002 |
0.002 |
0.002 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.2 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.0 |
||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Ketones (mg/dL) |
Neg |
2 |
- |
2 |
1 |
|
5 |
3 |
5 |
3 |
4 |
||
Blood (Ery/µL) |
Neg |
5 |
4 |
5 |
5 |
|
Ca80 |
- |
1 |
- |
- |
||
Protein (mg/dL) |
Neg |
3 |
- |
3 |
1 |
|
Trace |
2 |
4 |
1 |
4 |
||
30 |
- |
1 |
1 |
- |
||
Nitrite |
Neg |
4 |
4 |
5 |
1 |
|
Pos |
1 |
1 |
- |
4 |
||
Leucocytes |
Neg |
3 |
- |
3 |
1 |
|
Ca15 |
1 |
1 |
1 |
2 |
||
Ca70 |
1 |
3 |
1 |
2 |
||
Ca125 |
- |
1 |
- |
- |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
- |
2 |
1 |
|
>15 |
2 |
5 |
2 |
4 |
||
15 |
3 |
- |
1 |
- |
||
Microscopic Examination |
Epi Cells |
0 |
3 |
4 |
2 |
4 |
0-1 |
1 |
1 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
Casts |
Absent |
4 |
4 |
4 |
5 |
|
Present |
1 |
1 |
1 |
- |
||
Crystals |
Present |
5 |
5 |
5 |
5 |
M:
Male; SD: Standard Deviation; Pos: Positive; Neg: Negative; Ca:
Calculated.
>=:
Greater than or equal to; >: Greater than.
TABLE 18 (Contd…). SUMMARY OF URINALYSIS RECORD
Examination |
Group, Sex & Dose (mg/kg body weight/day) |
G1R, M & 0 |
G4R, M &1000 |
G1R, F & 0 |
G4R, F & 1000 |
|
Number of Animals (randomly selected) |
5 |
5 |
5 |
5 |
||
Physical Examination |
Color |
Pale Yellow |
2 |
5 |
3 |
3 |
Yellow |
3 |
- |
2 |
2 |
||
Appearance |
Clear |
3 |
2 |
4 |
4 |
|
Turbid |
2 |
3 |
1 |
1 |
||
Volume (mL) |
Mean |
6.4 |
8.6 |
7.9 |
7.8 |
|
±SD |
1.7 |
3.1 |
2.2 |
0.8 |
||
Chemical Examination |
pH |
Mean |
6.7 |
7.3 |
6.8 |
7.6 |
±SD |
0.9 |
0.4 |
1.0 |
1.0 |
||
Specific Gravity |
Mean |
1.020 |
1.014 |
1.014 |
1.012 |
|
±SD |
0.007 |
0.002 |
0.007 |
0.008 |
||
Urobilinogen (mg/dL) |
Mean |
0.2 |
0.2 |
0.2 |
0.6 |
|
±SD |
0.0 |
0.0 |
0.0 |
0.8 |
||
Bilirubin (mg/dL) |
Neg |
2 |
5 |
5 |
2 |
|
1 |
3 |
- |
- |
3 |
||
Ketones (mg/dL) |
Neg |
1 |
2 |
5 |
5 |
|
5 |
4 |
3 |
- |
- |
||
Blood (Ery/µL) |
Neg |
5 |
5 |
5 |
4 |
|
Ca10 |
- |
- |
- |
1 |
||
Protein (mg/dL) |
Neg |
2 |
5 |
4 |
2 |
|
Trace |
2 |
- |
1 |
- |
||
30 |
1 |
- |
- |
- |
||
100 |
- |
- |
- |
1 |
||
>=300 |
- |
- |
- |
2 |
||
Nitrite |
Neg |
3 |
5 |
5 |
5 |
|
Pos |
2 |
- |
- |
- |
||
Leucocytes |
Neg |
- |
1 |
3 |
2 |
|
Ca15 |
1 |
4 |
2 |
- |
||
Ca70 |
4 |
- |
- |
3 |
||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
|
Microalbumin (mg/dL) |
Neg |
- |
1 |
3 |
1 |
|
>15 |
3 |
- |
1 |
3 |
||
15 |
2 |
4 |
1 |
1 |
||
Microscopic Examination\ |
Epi Cells |
0 |
3 |
3 |
2 |
2 |
0-1 |
1 |
2 |
2 |
1 |
||
1-2 |
1 |
- |
1 |
- |
||
2-3 |
- |
- |
- |
2 |
||
Casts |
Absent |
5 |
2 |
5 |
4 |
|
Present |
- |
3 |
- |
1 |
||
Crystals |
Absent |
- |
2 |
1 |
2 |
|
Present |
5 |
3 |
4 |
3 |
M:
Male; F: Female; R: Recovery; SD: Standard Deviation; Pos: Positive;
Neg: Negative.
Ca: Calculated; >=: Greater than
or equal to; >: Greater than.
TABLE 19. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1, M & 0 |
Mean |
0.0667 |
0.2891 |
0.7915 |
3.3315 |
1.4198 |
1.3943 |
2.9537 |
2.1193 |
±SD |
0.0045 |
0.0466 |
0.2701 |
0.3035 |
0.1420 |
0.2048 |
0.2510 |
0.0321 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G2, M & 111 |
Mean |
0.0719 |
0.3589 |
0.8023 |
3.4284 |
1.4112 |
1.5033 |
2.8196 |
2.1336 |
±SD |
0.0094 |
0.0292 |
0.0928 |
0.1782 |
0.1365 |
0.1061 |
0.1723 |
0.0957 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G3, M & 333 |
Mean |
0.0709 |
0.4450* |
0.8041 |
3.3728 |
1.4195 |
1.4754 |
2.8317 |
2.1467 |
±SD |
0.0060 |
0.0665 |
0.1455 |
0.2771 |
0.1776 |
0.1560 |
0.1507 |
0.0446 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
|
G4, M & 1000 |
Mean |
0.0716 |
0.4129* |
0.8155 |
3.3454 |
1.5221 |
1.5218 |
3.0082 |
2.2033 |
±SD |
0.0115 |
0.1013 |
0.1404 |
0.2101 |
0.1812 |
0.3979 |
0.7565 |
0.1355 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
G1, M & 0 |
Mean |
10.0491 |
1.1499 |
1.6300 |
1.9467 |
0.0208 |
0.0296 |
±SD |
1.6192 |
0.1975 |
0.4468 |
0.1258 |
0.0014 |
0.0017 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
10.3930 |
1.1988 |
1.6027 |
2.0659 |
0.0197 |
0.0290 |
±SD |
0.4389 |
0.2552 |
0.3454 |
0.1175 |
0.0013 |
0.0020 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
10.6576 |
1.3430 |
1.7846 |
2.0478 |
0.0203 |
0.0301 |
±SD |
0.7376 |
0.3501 |
0.3700 |
0.1024 |
0.0009 |
0.0013 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
10.8065 |
1.2209 |
1.9124 |
2.0837 |
0.0205 |
0.0305 |
±SD |
2.8155 |
0.3931 |
0.5906 |
0.1492 |
0.0015 |
0.0023 |
|
n |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
0.0741 |
0.2781 |
0.7048 |
0.1738 |
0.5901 |
1.1848 |
±SD |
0.0083 |
0.0317 |
0.0646 |
0.0299 |
0.1167 |
0.1262 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
0.0884 |
0.2632 |
0.7503 |
0.1432* |
0.5097 |
1.1940 |
±SD |
0.0110 |
0.0345 |
0.1289 |
0.0332 |
0.1138 |
0.0729 |
|
n |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
0.0728 |
0.2267* |
0.6584 |
0.1291* |
0.5413 |
1.2001 |
±SD |
0.0094 |
0.0282 |
0.1051 |
0.0193 |
0.0886 |
0.0513 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
0.0775 |
0.2179* |
0.6109 |
0.1466* |
0.5283 |
1.3318 |
±SD |
0.0093 |
0.0063 |
0.0413 |
0.0190 |
0.1008 |
0.3482 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 22).
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
2.2668 |
2.0179 |
11.5641 |
1.2626 |
0.0179 |
0.0266 |
±SD |
0.1164 |
0.0746 |
0.5339 |
0.1185 |
0.0011 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
2.0463* |
2.0056 |
12.5985 |
1.5260 |
0.0183 |
0.0272 |
±SD |
0.1081 |
0.1131 |
2.0359 |
0.2954 |
0.0014 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
2.0269* |
1.9917 |
10.1148 |
1.3551 |
0.0176 |
0.0265 |
±SD |
0.0937 |
0.0552 |
1.8164 |
0.1082 |
0.0008 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
1.9230* |
2.0216 |
10.2708 |
1.3780 |
0.0180 |
0.0275 |
±SD |
0.0912 |
0.0446 |
1.3180 |
0.1188 |
0.0010 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
Kidneys |
Brain |
|
G1R, M & 0 |
Mean |
0.0671 |
0.2367 |
0.8804 |
3.3055 |
1.6954 |
1.6355 |
2.2619 |
2.0448 |
±SD |
0.0080 |
0.0348 |
0.0907 |
0.1930 |
0.0763 |
0.1477 |
0.3680 |
0.1172 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.0638 |
0.2709 |
0.7442* |
3.4656 |
1.6882 |
1.6050 |
2.3506 |
2.0483 |
±SD |
0.0051 |
0.0738 |
0.0528 |
0.1133 |
0.0690 |
0.3581 |
0.3464 |
0.1621 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
12.6730 |
1.3824 |
1.8300 |
2.0437 |
0.0207 |
0.0299 |
±SD |
1.2027 |
0.2475 |
0.4858 |
0.5420 |
0.0009 |
0.0015 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
12.5717 |
1.6038 |
1.8342 |
1.9398 |
0.0210 |
0.0306 |
±SD |
1.2099 |
0.1130 |
0.4887 |
0.0584 |
0.0011 |
0.0008 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
0.0706 |
0.2511 |
0.6464 |
0.1265 |
0.6499 |
1.0512 |
±SD |
0.0064 |
0.0443 |
0.0886 |
0.0164 |
0.0920 |
0.0882 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
0.0702 |
0.2467 |
0.6261 |
0.1543* |
0.6334 |
1.0135 |
±SD |
0.0121 |
0.0337 |
0.1113 |
0.0105 |
0.0853 |
0.0746 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 19 (Contd…). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, F & 0 |
Mean |
1.9138 |
2.0075 |
9.6308 |
1.8480 |
0.0185 |
0.0278 |
±SD |
0.0978 |
0.0986 |
0.9760 |
0.0946 |
0.0009 |
0.0014 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
1.8218 |
1.9767 |
8.6614 |
2.0609 |
0.0193 |
0.0271 |
±SD |
0.1551 |
0.0844 |
1.7719 |
0.4014 |
0.0014 |
0.0006 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20. SUMMARY
OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1, M & 0 |
Mean |
440.14 |
0.0150 |
0.0648 |
0.1748 |
0.7637 |
0.3257 |
0.3099 |
±SD |
38.09 |
0.0018 |
0.0115 |
0.0484 |
0.1095 |
0.0493 |
0.0251 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G2, M & 111 |
Mean |
433.53 |
0.0162 |
0.0812 |
0.1809 |
0.7928 |
0.3262 |
0.3390 |
±SD |
29.89 |
0.0021 |
0.0090 |
0.0188 |
0.0447 |
0.0319 |
0.0185 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G3, M & 333 |
Mean |
437.73 |
0.0159 |
0.0995* |
0.1797 |
0.7734 |
0.3250 |
0.3314 |
±SD |
26.65 |
0.0016 |
0.0135 |
0.0302 |
0.0792 |
0.0413 |
0.0427 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, M & 1000 |
Mean |
443.94 |
0.0156 |
0.0891* |
0.1779 |
0.7570 |
0.3432 |
0.3304 |
±SD |
38.78 |
0.0013 |
0.0124 |
0.0187 |
0.0592 |
0.0298 |
0.0626 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
M: Male; SD: Standard Deviation; n: Number of Animals.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, M & 0 |
Mean |
0.6591 |
0.4745 |
2.2336 |
0.2614 |
0.3768 |
0.4360 |
0.0047 |
0.0067 |
±SD |
0.0371 |
0.0334 |
0.2239 |
0.0389 |
0.1233 |
0.0428 |
0.0003 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G2, M & 111 |
Mean |
0.6380 |
0.4818 |
2.3449 |
0.2758 |
0.3681 |
0.4668 |
0.0044 |
0.0067 |
±SD |
0.0606 |
0.0272 |
0.0585 |
0.0505 |
0.0681 |
0.0350 |
0.0003 |
0.0006 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G3, M & 333 |
Mean |
0.6350 |
0.4812 |
2.3924 |
0.3052 |
0.4081 |
0.4594 |
0.0046 |
0.0069 |
±SD |
0.0467 |
0.0237 |
0.2415 |
0.0710 |
0.0824 |
0.0376 |
0.0001 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
|
G4, M & 1000 |
Mean |
0.6545 |
0.4865 |
2.3426 |
0.2767 |
0.4271 |
0.4575 |
0.0045 |
0.0069 |
±SD |
0.1286 |
0.0618 |
0.4199 |
0.0940 |
0.1161 |
0.0285 |
0.0002 |
0.0004 |
|
n |
5 |
5 |
5 |
12 |
12 |
5 |
5 |
12 |
M: Male; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
|
G1, F & 0 |
Mean |
305.54 |
0.0242 |
0.0912 |
0.2307 |
0.0571 |
0.1938 |
0.3872 |
±SD |
21.99 |
0.0035 |
0.0163 |
0.0360 |
0.0100 |
0.0422 |
0.0618 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G2, F & 111 |
Mean |
314.85 |
0.0286 |
0.0853 |
0.2428 |
0.0458* |
0.1635 |
0.3854 |
±SD |
19.21 |
0.0044 |
0.0142 |
0.0457 |
0.0115 |
0.0448 |
0.0220 |
|
n |
12 |
5 |
5 |
5 |
12 |
11@ |
5 |
|
G3, F & 333 |
Mean |
302.78 |
0.0236 |
0.0730 |
0.2142 |
0.0431* |
0.1801 |
0.3879 |
±SD |
22.49 |
0.0038 |
0.0045 |
0.0429 |
0.0092 |
0.0352 |
0.0151 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
|
G4, F & 1000 |
Mean |
306.64 |
0.0245 |
0.0690* |
0.1938 |
0.0483 |
0.1749 |
0.4241 |
±SD |
25.44 |
0.0033 |
0.0062 |
0.0238 |
0.0080 |
0.0430 |
0.1222 |
|
n |
12 |
5 |
5 |
5 |
12 |
12 |
5 |
F: Female; SD: Standard Deviation; n: Number of Animals.
@: One animal data from group G1 and G2 is excluded for mean calculations as the weight varies from normal uterus due to presence of dead foetus during necropsy, but the data is presented in individual animal data. (Appendix 23).
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1, F & 0 |
Mean |
0.7409 |
0.6583 |
3.7703 |
0.4138 |
0.0058 |
0.0087 |
±SD |
0.0909 |
0.0663 |
0.3600 |
0.0696 |
0.0003 |
0.0005 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G2, F & 111 |
Mean |
0.6618 |
0.6488 |
4.0668 |
0.4903 |
0.0059 |
0.0087 |
±SD |
0.0563 |
0.0584 |
0.6665 |
0.0770 |
0.0002 |
0.0009 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G3, F & 333 |
Mean |
0.6560 |
0.6443 |
3.2646 |
0.4388 |
0.0057 |
0.0088 |
±SD |
0.0476 |
0.0330 |
0.5652 |
0.0452 |
0.0002 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
|
G4, F & 1000 |
Mean |
0.6097* |
0.6402 |
3.2355 |
0.4353 |
0.0057 |
0.0090 |
±SD |
0.0642 |
0.0516 |
0.3329 |
0.0373 |
0.0008 |
0.0007 |
|
n |
5 |
5 |
5 |
5 |
5 |
12 |
F: Female; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…). SUMMARY OF TERMINAL BODY WEIGHT (g) AND
ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Testes |
Epididymides |
Heart |
|
G1R, M & 0 |
Mean |
496.58 |
0.0136 |
0.0476 |
0.1785 |
0.6684 |
0.3430 |
0.3320 |
±SD |
40.88 |
0.0022 |
0.0051 |
0.0257 |
0.0554 |
0.0286 |
0.0478 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
502.58 |
0.0127 |
0.0538 |
0.1482* |
0.6902 |
0.3358 |
0.3184 |
±SD |
12.09 |
0.0010 |
0.0137 |
0.0126 |
0.0356 |
0.0088 |
0.0643 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Kidneys |
Brain |
Liver |
Prostate |
Seminal vesicles with coagulating glands |
Lungs |
Pituitary |
Thyroid along with parathyroid# |
|
G1R, M & 0 |
Mean |
0.4554 |
0.4147 |
2.5665 |
0.2783 |
0.3746 |
0.4088 |
0.0042 |
0.0060 |
±SD |
0.0586 |
0.0488 |
0.3239 |
0.0415 |
0.1185 |
0.0840 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, M & 1000 |
Mean |
0.4682 |
0.4080 |
2.4984 |
0.3193 |
0.3643 |
0.3862 |
0.0042 |
0.0061 |
±SD |
0.0730 |
0.0361 |
0.1858 |
0.0248 |
0.0941 |
0.0153 |
0.0002 |
0.0003 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
M: Male; R: Recovery; SD: Standard Deviation; n: Number of Animals; #: Weighed post fixation.
TABLE 20 (Contd…).
SUMMARY OF TERMINAL BODY WEIGHT (g) AND ORGAN WEIGHT RELATIVE TO
TERMINAL BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
|
Terminal Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Ovaries |
Uterus with Cervix |
Heart |
G1R, F & 0 |
Mean |
308.17 |
0.0229 |
0.0822 |
0.2106 |
0.0410 |
0.2112 |
0.3432 |
±SD |
16.88 |
0.0016 |
0.0185 |
0.0336 |
0.0043 |
0.0292 |
0.0498 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
G4R, F & 1000 |
Mean |
311.82 |
0.0225 |
0.0791 |
0.2015 |
0.0495* |
0.2026 |
0.3256 |
±SD |
12.71 |
0.0037 |
0.0102 |
0.0405 |
0.0029 |
0.0205 |
0.0293 |
|
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
F: Female; R: Recovery; SD: Standard Deviation; n: Number of Animals; *: Statistically significant (P<0.05) change than the vehicle control group.
Applicant's summary and conclusion
- Conclusions:
- In conclusion, the oral administration of test item over the time of the study, carried out according to the OECD guideline 422 (for main group males with a total of 31 days, for main group females ranging from 50 to 62 days and for recovery group animals with a total period of 52 days) did not produce any indication of systemic, reproduction and developmental toxicity at the dose levels of 111, 333 and 1000 mg/kg body weight/day under experimental conditions employed.
Therefore, the no-observed-adverse-effect-level (NOAEL) of test item is considered as 1000 mg/kg body weight for systemic, reproduction and developmental toxicity end points. - Executive summary:
The objective of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test of the test item by oral gavage in Sprague Dawley Rats was to determine the possible health hazards likely to arise from repeated exposure to the test item over a relatively limited period of time. This study was also conducted to provide initial information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition and an estimate of the No Observed Adverse Effect Level (NOAEL).
A total of 116 (58 males + 58 females) Sprague Dawley rats were selected for the study and distributed to four main (G1, G2, G3 and G4) and two recovery groups (G1R and G4R). Each main group consisted of 12 males and 12 females and each recovery group consisted of 5 males and 5 females. The animals in group G1/G1R were administered with vehicle [0.5% w/v Carboxymethyl Cellulose], animals in groups G2, G3 and G4/G4R were administered with test item at the dose levels of 111, 333 and 1000 mg/kg body weight/day for low, mid and high/high dose recovery, respectively. Vehicle and test item formulations were administered orally by gavage with the dose volume of
10 mL/kg body weight/day once daily at similar times on each day for 7 days a week.All the main group males were administered with test item during pre-mating (14-days), during mating and during post-mating period (total of 31 days). The pregnant females from main groups were administered with test item during pre-mating (14-days), during mating, pregnancy (gestation) and up to lactation day 13.The females with positive mating signal, but no-evidence of pregnancy / litteringwere administered with test itemduringpre-mating (14-days),during mating, and further 24 days from the day of positive mating signal. All the recovery group animals were administered with test item for 50 days followed by a 14-day observation period without treatment.
The test item formulations werestable for 6 hours and 48 hours at room temperature in 0.5% w/v Carboxymethyl Cellulose with the concentrations of 5 mg/mL and 100 mg/mL.The homogeneity and dose form concentration analysis for preparedtest item formulations during treatment periodwas performed during week 1 and 5 and the mean results were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) is less than 15%.
For systemic toxicity assessment, all the animals (main and recovery groups) of both sexes were observed once daily for clinical signs, twice daily for mortality and morbidity and once in a week for detailed clinical examination. Body weight of all the animals (main and recovery groups) of both sexes were recorded once in a week until termination. Further, the body weight of all pregnant females was recorded on gestation day (GD) 0, 7, 14 and 20 during pregnancy and on lactation day (LD) 1, 4, 7, 13 and 14 during lactation.Body weight of all non-pregnant females was recorded once in a week until termination. Feed consumption for all the animals of both sexes were recorded once in a week during pre-mating for main groups and throughout the experimental period for recovery groups. Further, feed consumption of all pregnant females was recorded during GD 0 to 7, 7 to 14 and 14 to 20 and during LD 1 to 4, 4 to 7 and 7 to 13.Ophthalmological examination was carried out once before treatment and at the end of the dosing period for all males and females (main and recovery groups). Neurological/functional observations were performed for five randomly selected males and females from each main group, for all animals from recovery groups towards end of the dosing period. The investigations of haematology and clinical chemistry for all animals (main and recovery groups), investigations of urinalysis for five randomly selected males from each main group and for all recovery groups animals was conducted at termination. Serum thyroxine hormone (T4) levels were estimated for all main group males by ELISA. The organs were collected and weighed on the day of termination for all animals (main and recovery groups) of both sexes and organ weight relative to terminal body weight was calculated. All the animals (main and recovery groups) of both sexes were observed for both external and internal gross pathological changes during conduct of necropsy. Histopathological examination was conducted on all the tissues collected from the groups G1 and G4 animals with special emphasis on stages of spermatogenesis in the male gonads and histopathology of interstitial testicular cell structure.
For reproductive toxicity assessment, all the males (main groups) were evaluated for reproductive performances such as, mating and fertility indices. All the females (main groups) were evaluated for reproductive performances such as, mating, fertility, gestation and parturition indices. The females were also evaluated for pre-coital interval and gestation length. All females were evaluated for oestrus cyclicity during pre-mating period and the vaginal smear examination was continued until evidence of mating. At birth (delivery) parameters such as, number of live/dead pups born, litter size, sex ratio (m/f) and live birth index per litter were observed / calculated. The litter observations during lactation period such as, number of survived or dead pups, sex ratio (m/f) and pup survival index per litter were observed / calculated. The total number of implantation sites was recorded for each litter during necropsy and the post-implantation and postnatal losses per litter was calculated.
For developmental toxicity assessment, all survived pups from each litter were observed once daily for external behavioural changes and twice daily for mortality until termination [postnatal day (PND) 13]. All pups from each litter were weighed individually on PND 1, 4, 7 and 13 and measured for anogenital distance on PND 4. All male pups were observed for retention of nipples on PND 13. All the pups were subjected for both external and internal gross pathological changes during conduct of necropsy. The collected serum from PND 13 pups was subjected to estimation of thyroxine hormone (T4) levels using ELISA.
There were no clinical signs of toxicity and no mortality/morbidity noted in any of the animals from all the tested dose groups, howeverdark purple colored faeces were noted from day 2 observation throughout the experiment period till termination of treatment in group G3 & G4/G4Ranimals. This coloration is due to colored nature of the test item but not any adverse sign. Detailed clinical examination did not reveal any changes in any of the tested dose group animals. No changes noted in mean body weight, percent change in mean body weight gain and mean feed consumption in all the tested dose groups of both sexes. The ophthalmological examination and neurological/functional examinations did not reveal any test item-related changes in any of the animals from all the tested dose groups of both sexes. The obtained mean haematology, clinical chemistry and urinalysis values did not reveal any test item-related changes in all the tested dose groups. The estimated serum T4 levels did not reveal any changes. The absolute and relative organ weights of both sexes did not reveal any changes from all the tested dose groups.
No treatment related gross pathological changes were noted in any of the animals from all the tested dose groups during necropsy, however in test item administered animals of both sexes, the contents of gastrointestinal tract were found to be violet in color which was attributed to the color of the test item and was considered as non-adverse effect as the mucosa of gastrointestinal tract was found to be within normal limits.
No treatment related microscopic findings noted in any of the tissues/organs subjected for histopathological evaluation from both high dose group and vehicle control group animals of both sexes.
There were no effects noted on reproductive performance of both sexes in all the tested dose groups. No test item-related irregularities observed in oestrus cyclicity of the females from all the tested dose groups during treatment period. No changes were noted in ‘at birth’ (delivery) and or ‘litter observations’ in all the tested dose groups. No effects were noted for live birth index and pup survival index in all the tested dose groups. No test item-related post-implantation losses were noted in all the tested dose groups.
There were no developmental/external behavioural changes noted and no test item-related mortalities noted during postnatal period in any of pups from all the tested dose group litters. The mean pup weight, mean anogenital distance and its ratio in either sex of pups per litter were un-affected by the test item in all the tested dose groups. There were no incidences of retention of nipples in male pups examined on PND 13 from all the tested dose and control group litters. The estimated serum T4 levels of PND 13 (from all litters) pups did not reveal any changes in all the tested dose group litters. There were no gross pathological changes noted in any of the pups during scheduled sacrifice from all the tested dose and control group litters
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