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EC number: 947-922-8 | CAS number: -
- 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
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- 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:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 april 2018 to 08 June 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted on 03 October 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Reaction products of alcohols, C11-14-iso, C13 rich and phosphorus pentoxide
- EC Number:
- 947-922-8
- Molecular formula:
- n.a. (UVCB)
- IUPAC Name:
- Reaction products of alcohols, C11-14-iso, C13 rich and phosphorus pentoxide
- Test material form:
- liquid
- Details on test material:
- clear yellowish liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and batch No.of test material: DEG4 410913
- Expiration date of the batch: 2019-02-22
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 vehicle: soluble in corn oil and The stability of the test item Hostacor ITD in dose formulations was established under Bioneeds Study No.: BIO-ANM 813. As per the stability results, the test item formulations at the concentrations of 1 mg/mL and 100 mg/mL are stable up to 6 hours at room temperature
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- Rat is one of the recommended species by regulatory agencies for conducting preclinical toxicological studies among rodents
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 7 weeks
- Weight at study initiation: Males: 130.07 g to 149.99 g
Females: 122.05 g to 140.00 g
- Housing: L430 X B285 X H150 mm
- Diet (e.g. ad libitum): Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG)
- Water (e.g. ad libitum): Deep bore-well water passed through Reverse Osmosis Unit
- Acclimation period: 06 April 2018 to 11 April 2018
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4°C to 23.3°C
- Humidity (%): 41% to 66%
- 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: 12 april 2018 To: 09 May 2019
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- The test item was administered through oral route using stainless steel (gavage) cannula as it is the probable route in human
- Vehicle:
- corn oil
- Details on oral exposure:
VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil was used as vehicle for the preparation of formulations as evidenced by the in-house miscibility test results. Corn oil is the universally accepted vehicle in preclinical formulations- 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 done by Analytical Chemistry department of Bioneeds India Private Limited. The analysis was done as per methods detailed in the Study Plan No. BIO-ANM 813 and the results are presented in the report. Sampling and analysis of formulations was performed during week 1 and week 4 of the treatment. The samples were collected in duplicates from top, middle and bottom layer from low, mid and high dose concentrations, in duplicates from middle layer from vehicle control.
The collected samples were transferred to Analytical Chemistry department of Bioneeds India Private Limited for dose concentration analysis. One set of aliquot of each formulation was analyzed. The second set of samples was discarded as the analysis results of first set of samples were within the range of 85 to 115% of the nominal concentration and the relative standard deviation (% RSD) was ≤10%. - Duration of treatment / exposure:
- 28 consecutive days
- Frequency of treatment:
- 28 consecutive days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle control / Vehicle control recovery
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Low dose
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Mid dose
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- High dose/ High dose recovery
- No. of animals per sex per dose:
- 5 males and 5 females per sex per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses of 100, 300 and 1000 mg/kg body weight was selected as low (G2), mid (G3) and high dose (G4/G4R) levels for test item Hostacor ITD based on the results obtained from the dose range finding study (Bioneeds Study Number: BIO-TX 3133).
- Rationale for animal assignment: randomised
- Post-exposure recovery period in satellite groups: 14 days recovery period - Positive control:
- Not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once daily
- Cage side observations checked in table [No.1] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly once
BODY WEIGHT: Yes
- Time schedule for examinations: weekly once
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before start of the treatment and during week 4 of treatment for G1 and G4 group animals and during week 6 for recovery group animals (G1R and G4R)
- Dose groups that were examined: G1/G1R and G4/G4R
HAEMATOLOGY: Yes
- Time schedule for collection of blood: main groups on day 29 and from recovery group animals on day 43
- Anaesthetic used for blood collection: Yes
- Animals fasted: Yes
- How many animals: all the animals
- Parameters checked in table [No.11] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: main groups on day 29 and from recovery group animals on day 43
- Animals fasted: Yes
- How many animals: all the animals
- Parameters checked in table [No.12] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: main groups on day 29 and from recovery group animals on day 43
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table [No.13] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 4 for all the main group animals and during week 6 for recovery group animals (G1R and G4R)
- Dose groups that were examined: G1 to G4, G1R and G4R
- Battery of functions tested: sensory activity / grip strength / motor activity
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 16)
HISTOPATHOLOGY: Yes (see table 17) - Statistics:
- SPSS software version 22. One way ANOVA followed by Dunnett’s post test were done for different treatment and recovery groups comparing with the respective control group data. Data of recovery groups during recovery period was subjected to student’s t-test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No relevant clinical signs of toxicity was observed in any of the vehicle or test item administered animals up to the high dose group. A slight wet perineum was observed in a few high dose test item administered animals (males: 2/5 and females: 2/5 in main group animals; males: 1/5 and females: 2/5 in recovery group animals) which is not considered to be of toxicological relevance
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- No relevant clinical signs of toxicity was observed in any of the vehicle or test item administered animals up to the high dose group. A slight wet perineum was observed in a few high dose test item administered animals (males: 2/5 and females: 2/5 in main group animals; males: 1/5 and females: 2/5 in recovery group animals) which is not considered to be of toxicological relevance
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related changes in mean body weight and body weight gain (percent change in body weight with respect to Day 1) were noted. However, statistical significant decrease in mean body weight was observed on days 8, 15, 22 and 28 in G4 males and statistical significant decrease in percent change in body weight with respect to Day 1 was observed in G4 males during Day 1-8 to Day 1-28, and in G4R females during Day 1-8. All these changes are considered as incidental due to lack of dose dependency and also no concomitant changes were observed in feed consumption
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related changes in hematology parameters were noted.
A non-dose dependent statistically significant increase in percent and absolute monocytes in G3 males; increase in percent and absolute neutrophils in G4 males; decrease in percent lymphocytes in G4 males was observed. Statistical significant increase in percent and absolute neutrophils in G4 females; increase in percent and absolute monocytes in G4 females; decrease in percent lymphocytes in G4 females was observed. However, in the absence of significant variations in total leukocyte counts, the observed variations are considered incidental and also no such changes were noted at the end of recovery period.
At the end of recovery period, statistical significant increase in Haemoglobin, Mean corpuscular hemoglobin and Mean corpuscular haemoglobin concentration observed in G4 females are considered incidental and not related to treatment as these range of values are minimal and also similar changes were not noticed in main group animals - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In males, the non-dose dependent decrease in creatinine and A/G ratio in G3; decrease in urea and BUN in G2 and G3; decrease in cholesterol and calcium in G4; increase in ALP in G3 and increase in AST in G4 was observed. In females, statistically significant decrease in cholesterol, total protein, cholinesterase and globulin in G4; statistically significant increase ALP in G2, G3 and G4; increase in total bilirubin and ALT in G4 was noted. All these clinical chemistry variations are considered as incidental as there were no corresponding histopathological findings observed at high dose group animals
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related changes were observed in neurological/functional examination battery carried out during Week 4 for main group and Week 6 for recovery group animals. Statistical significant decrease in movement counts noted in G4 males was considered incidental due to lack of dose dependency and also none of the neuromuscular parameters
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In males, statistically significant increase in absolute and relative spleen weight in G2, increase in absolute and relative weight of Prostate+Seminal vesicles and coagulating gland in G3, increase in absolute epididymis and testes weight in G3, increase in absolute heart, kidneys and liver weight in G2 and G3 was noted. The statistical significant decrease in fasting body weight in G4, increase in relative kidneys and liver weight in G2, G3 and G4, increase in relative heart weight in G3 and increase in relative epididymis and testes weight in G4 was noted.
In females, statistical significant increase in absolute and relative kidneys weight in G4, increase in absolute liver weight in G4 and relative liver weight in G3 and G4 was noted.
All these observed changes are considered as incidental and not related to treatment as there were no corresponding histopathological findings observed at the high dose group. Also, a statistical significant increase in absolute and relative adrenals weight was observed in G4R animals is considered as incidental not related to treatment as these effects were not observed in main group animals - Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Lesions observed in animals from high dose group were MNC infiltration in liver, tubular basophilia in kidneys and perivascular MNC infiltration in lungs. Similar findings were also noticed in concurrent control group. Hence, these lesions were considered as spontaneous or background lesions.
A detailed qualitative examination of the testes was made taking into account the tubular stages of the spermatogenic cycle. The examination was conducted in order to identify treatment related effects such as missing germ cell layers or types, retained spermatids, multinucleate or apoptotic germ cells and sloughing of spermatogenic cells into the lumen or any cell or stage specificity of testicular findings
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
TABLE 1. SUMMARY OF CLINICAL SIGNS, MORTALITY AND DETAILED CLINICAL EXAMINATION RECORD
Group, Sex & Dose (mg/kg body weight/day) |
No. of Animals |
Clinical Sign(s)/ Number of Animals revealed |
Mortality (No. of incidence/ No. of animals) |
||||
G1, M & 0 |
5 |
N |
0/5 |
||||
G2, M & 100 |
5 |
N |
0/5 |
||||
G3, M & 300 |
5 |
N |
0/5 |
||||
G4, M & 1000 |
5 |
73+/2, N/3 |
0/5 |
||||
G1R, M & 0 |
5 |
N |
0/5 |
||||
G4R, M & 1000 |
5 |
73+/1, N/4 |
0/5 |
G: Group; M: Male; N: Normal; 73: Wet perineum; +: Slight; R: Recovery.
TABLE 1 (Contd..,). SUMMARY OF CLINICAL SIGNS, MORTALITY AND DETAILED CLINICAL EXAMINATION RECORD
Group, Sex & Dose (mg/kg body weight/day) |
No. of Animals |
Clinical Sign(s)/ Number of Animals revealed |
Mortality (No. of incidence/ No. of animals) |
||||
G1, F & 0 |
5 |
N |
0/5 |
||||
G2, F & 100 |
5 |
N |
0/5 |
||||
G3, F & 300 |
5 |
N |
0/5 |
||||
G4, F & 1000 |
5 |
73+/2, N/3 |
0/5 |
||||
G1R, F & 0 |
5 |
N |
0/5 |
||||
G4R, F & 1000 |
5 |
73+/2, N/3 |
0/5 |
G: Group; F: Female; N: Normal; 73: Wet perineum; +: Slight; R: Recovery.
TABLE 2. SUMMARY OF DETAILED CLINICAL EXAMINATION RECORD
Group: G4 Dose: 1000 mg/kg body weight/day Days: 15, 22 & 28
Examination |
Sex |
Male & Female |
|||
1. Skin & Fur |
0 |
||||
2. Eye Discharge |
0 |
||||
3. Mucous Membrane |
0 |
||||
4. Occurrence of Secretions & Excretions |
a. Salivation |
0 |
|||
b. Urine Staining |
1* (2-M & 2-F) |
||||
c. Fecal Staining or Diarrhoea |
0 |
||||
d. Nasal Discharge |
0 |
||||
5. Autonomic Activity |
a. Lacrimation |
0 |
|||
b. Piloerection |
0 |
||||
c. Pupillary Response |
1 |
||||
d. Un-usual Respiratory Pattern |
0 |
||||
6. Response to Handling |
1 |
||||
7. Changes in Gait |
0 |
||||
8. Posture |
0 |
||||
9. Clonic or Tonic Movements |
0 |
||||
10. Stereotypies |
a. Repetitive Circling |
0 |
|||
b. Excessive Grooming |
0 |
||||
11.Bizarre behavior |
a. Self-mutilation |
0 |
|||
b. Walking Backwards |
0 |
||||
12. Hair Thinning with Hair Re-growth |
0 |
0: Absent; 1: Present; *: slight wet perineum; M: Male; F: Female.
TABLE 2 (Contd..,) SUMMARY OF DETAILED CLINICAL EXAMINATION RECORD
Group: G4R Dose: 1000 mg/kg body weight/day Days: 15, 22 & 28
Examination |
Sex |
Male & Female |
|||
1. Skin & Fur |
0 |
||||
2. Eye Discharge |
0 |
||||
3. Mucous Membrane |
0 |
||||
4. Occurrence of Secretions & Excretions |
a. Salivation |
0 |
|||
b. Urine Staining |
1* (1-M & 2-F) |
||||
c. Fecal Staining or Diarrhoea |
0 |
||||
d. Nasal Discharge |
0 |
||||
5. Autonomic Activity |
a. Lacrimation |
0 |
|||
b. Piloerection |
0 |
||||
c. Pupillary Response |
1 |
||||
d. Un-usual Respiratory Pattern |
0 |
||||
6. Response to Handling |
1 |
||||
7. Changes in Gait |
0 |
||||
8. Posture |
0 |
||||
9. Clonic or Tonic Movements |
0 |
||||
10. Stereotypies |
a. Repetitive Circling |
0 |
|||
b. Excessive Grooming |
0 |
||||
11.Bizarre behavior |
a. Self-mutilation |
0 |
|||
b. Walking Backwards |
0 |
||||
12. Hair Thinning with Hair Re-growth |
0 |
0: Absent; 1: Present; *: slight wet perineum; M: Male; F: Female.
TABLE 3.SUMMARY OF BODY WEIGHTS (g)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Days |
|||||||||||||||||
1 |
8 |
15 |
22 |
28 |
35 |
42 |
||||||||||||
G1, M & 0 |
Mean |
174.07 |
209.29 |
236.88 |
271.53 |
291.43 |
- |
- |
||||||||||
±SD |
8.29 |
12.08 |
18.65 |
22.28 |
27.55 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G2, M & 100 |
Mean |
172.73 |
211.66 |
239.60 |
266.86 |
293.48 |
- |
- |
||||||||||
±SD |
7.91 |
12.32 |
18.56 |
19.06 |
21.78 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G3, M & 300 |
Mean |
176.21 |
212.58 |
244.39 |
273.80 |
299.72 |
- |
- |
||||||||||
±SD |
7.30 |
12.37 |
15.26 |
14.44 |
17.50 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G4, M & 1000 |
Mean |
176.36 |
189.75* |
206.52* |
224.04* |
251.00* |
- |
- |
||||||||||
±SD |
8.17 |
5.69 |
13.62 |
12.48 |
12.31 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G1R, M & 0 |
Mean |
174.11 |
208.03 |
243.25 |
267.42 |
295.11 |
336.49 |
344.25 |
||||||||||
±SD |
8.39 |
15.14 |
22.49 |
26.45 |
26.35 |
32.11 |
33.85 |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||
G4R, M & 1000 |
Mean |
173.58 |
200.74 |
225.96 |
257.62 |
279.12 |
320.29 |
326.71 |
||||||||||
±SD |
6.03 |
9.39 |
14.13 |
16.03 |
20.04 |
18.47 |
19.00 |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; -: Not Applicable
*: Statistically significant (p<0.05)
TABLE 3 (Contd..,) SUMMARY OF BODY WEIGHTS (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Body Weight (g) on Days |
|||||||||||||||||
1 |
8 |
15 |
22 |
28 |
35 |
42 |
||||||||||||
G1, F & 0 |
Mean |
154.53 |
176.53 |
195.19 |
208.48 |
221.06 |
- |
- |
||||||||||
±SD |
8.20 |
11.12 |
17.10 |
16.78 |
18.79 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G2, F & 100 |
Mean |
156.49 |
181.40 |
197.76 |
209.43 |
220.60 |
- |
- |
||||||||||
±SD |
6.28 |
5.96 |
6.66 |
6.75 |
8.44 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G3, F & 300 |
Mean |
156.49 |
180.41 |
195.66 |
208.53 |
223.71 |
- |
- |
||||||||||
±SD |
9.18 |
9.88 |
6.24 |
7.03 |
6.92 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G4, F & 1000 |
Mean |
156.21 |
171.64 |
187.95 |
202.06 |
215.70 |
- |
- |
||||||||||
±SD |
8.41 |
11.37 |
17.06 |
16.75 |
16.90 |
- |
- |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
- |
- |
|||||||||||
G1R, F & 0 |
Mean |
155.81 |
179.12 |
191.93 |
207.70 |
218.68 |
245.02 |
248.74 |
||||||||||
±SD |
5.45 |
9.37 |
9.72 |
9.29 |
10.75 |
9.75 |
10.14 |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||
G4R, F & 1000 |
Mean |
156.07 |
169.48 |
184.50 |
201.39 |
219.60 |
246.26 |
249.13 |
||||||||||
±SD |
6.50 |
8.50 |
6.25 |
12.48 |
18.03 |
15.06 |
15.46 |
|||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; -: Not Applicable
TABLE 4. SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight (%) during Days |
|||||||||||||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
1 to 35 |
1 to 42 |
|||||||||||
G1, M & 0 |
Mean |
20.19 |
35.96 |
55.83 |
67.20 |
- |
- |
|||||||||
±SD |
1.64 |
5.42 |
6.65 |
9.42 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G2, M & 100 |
Mean |
22.50 |
38.58 |
54.39 |
69.79 |
- |
- |
|||||||||
±SD |
2.96 |
5.41 |
5.54 |
6.96 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G3, M & 300 |
Mean |
20.61 |
38.66 |
55.37 |
70.02 |
- |
- |
|||||||||
±SD |
3.66 |
5.24 |
4.18 |
4.10 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G4, M & 1000 |
Mean |
7.68* |
17.31* |
27.22* |
42.56* |
- |
- |
|||||||||
±SD |
2.96 |
9.75 |
8.82 |
9.65 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G1R, M & 0 |
Mean |
19.39 |
39.56 |
53.39 |
69.30 |
93.05 |
97.47 |
|||||||||
±SD |
4.00 |
8.03 |
9.64 |
8.73 |
12.03 |
12.73 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, M & 1000 |
Mean |
15.64 |
30.09 |
48.33 |
60.68 |
84.47 |
88.15 |
|||||||||
±SD |
3.01 |
4.44 |
5.06 |
7.28 |
7.01 |
6.57 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n: Number of animals; -: Not Applicable
*: Statistically significant (p<0.05)
TABLE 4 (Contd..,). SUMMARY OF PERCENT CHANGE IN BODY WEIGHT (%) WITH RESPECT TO DAY 1 RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Percent Change in Body Weight (%) during Days |
|||||||||||||||
1 to 8 |
1 to 15 |
1 to 22 |
1 to 28 |
1 to 35 |
1 to 42 |
|||||||||||
G1, F & 0 |
Mean |
14.21 |
26.24 |
34.85 |
42.98 |
- |
- |
|||||||||
±SD |
2.40 |
7.10 |
6.58 |
7.67 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G2, F & 100 |
Mean |
15.96 |
26.44 |
33.91 |
41.04 |
- |
- |
|||||||||
±SD |
2.47 |
3.63 |
3.98 |
4.66 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G3, F & 300 |
Mean |
15.36 |
25.21 |
33.44 |
43.24 |
- |
- |
|||||||||
±SD |
3.79 |
4.34 |
4.57 |
7.27 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G4, F & 1000 |
Mean |
9.84 |
20.25 |
29.33 |
38.09 |
- |
- |
|||||||||
±SD |
2.31 |
7.44 |
7.44 |
7.89 |
- |
- |
||||||||||
n |
5 |
5 |
5 |
5 |
- |
- |
||||||||||
G1R, F & 0 |
Mean |
14.91 |
23.14 |
33.36 |
40.39 |
57.35 |
59.72 |
|||||||||
±SD |
2.94 |
2.97 |
5.66 |
6.36 |
6.93 |
6.46 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 1000 |
Mean |
8.61* |
18.30 |
29.03 |
40.60 |
57.77 |
59.64 |
|||||||||
±SD |
3.58 |
3.73 |
5.36 |
7.90 |
6.43 |
7.30 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n: Number of animals; -: Not Applicable
*: Statistically significant (p<0.05)
TABLE 5. SUMMARY OF FEED CONSUMPTION (g/rat/day)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
||||||||||
G1, M & 0 |
Mean |
19.22 |
19.40 |
20.06 |
22.48 |
- |
- |
|||||||||
±SD |
3.62 |
3.27 |
3.96 |
3.49 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G2, M & 100 |
Mean |
17.79 |
17.97 |
18.30 |
21.21 |
- |
- |
|||||||||
±SD |
2.67 |
2.62 |
2.97 |
2.61 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G3, M & 300 |
Mean |
17.98 |
18.27 |
18.95 |
21.04 |
- |
- |
|||||||||
±SD |
2.80 |
2.29 |
2.54 |
2.10 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G4, M & 1000 |
Mean |
16.03 |
16.10 |
17.28 |
20.18 |
- |
- |
|||||||||
±SD |
1.04 |
0.51 |
0.73 |
1.03 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G1R, M & 0 |
Mean |
19.42 |
19.60 |
20.31 |
22.32 |
20.23 |
19.44 |
|||||||||
±SD |
3.73 |
4.15 |
4.52 |
4.66 |
3.82 |
3.27 |
||||||||||
n |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
G4R, M & 1000 |
Mean |
16.31 |
16.86 |
17.57 |
20.50 |
19.14 |
18.20 |
|||||||||
±SD |
0.74 |
0.90 |
1.78 |
2.61 |
3.39 |
2.99 |
||||||||||
n |
2 |
2 |
2 |
2 |
2 |
2 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation, n: Number of cages; -: Not Applicable
TABLE 5 (Contd..,). SUMMARY OF FEED CONSUMPTION (g/rat/day)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Week 1 |
Week 2 |
Week 3 |
Week 4 |
Week 5 |
Week 6 |
||||||||||
G1, F & 0 |
Mean |
16.14 |
17.17 |
17.65 |
19.61 |
- |
- |
|||||||||
±SD |
1.22 |
1.33 |
1.36 |
1.74 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G2, F & 100 |
Mean |
14.55 |
14.55 |
14.98 |
16.62 |
- |
- |
|||||||||
±SD |
1.75 |
1.55 |
1.99 |
1.84 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G3, F & 300 |
Mean |
13.74 |
14.59 |
15.37 |
17.52 |
- |
- |
|||||||||
±SD |
1.47 |
1.24 |
1.58 |
2.24 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G4, F & 1000 |
Mean |
12.05 |
13.05 |
12.98 |
14.48 |
- |
- |
|||||||||
±SD |
1.06 |
2.17 |
2.21 |
1.83 |
- |
- |
||||||||||
n |
2 |
2 |
2 |
2 |
- |
- |
||||||||||
G1R, F & 0 |
Mean |
14.72 |
15.57 |
16.46 |
17.22 |
16.48 |
16.57 |
|||||||||
±SD |
0.92 |
1.09 |
1.08 |
1.57 |
1.74 |
0.66 |
||||||||||
n |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
G4R, F & 1000 |
Mean |
11.88 |
12.55 |
12.31 |
14.67 |
13.58 |
14.04 |
|||||||||
±SD |
0.76 |
1.47 |
1.30 |
2.55 |
2.16 |
2.52 |
||||||||||
n |
2 |
2 |
2 |
2 |
2 |
2 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n: Number of cages; -: Not Applicable
TABLE 6. SUMMARY OF OPHTHALMOSCOPIC EXAMINATION RECORD
Week 4 |
|||||||||||||||||||
Group & Sex |
G1 & M |
G4 & M |
G1 & F |
G4 & F |
|||||||||||||||
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
|||||||||||||||
No. of Animals |
5 |
5 |
5 |
5 |
|||||||||||||||
Observations |
|||||||||||||||||||
Eye Parameters ↓ |
L |
R |
L |
R |
L |
R |
L |
R |
|||||||||||
Adnexa |
Lids |
N |
N |
N |
N |
N |
N |
N |
N |
||||||||||
Ducts |
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 |
Vessels |
N |
N |
N |
N |
N |
N |
N |
N |
||||||||||
Macula |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Tapetum lucidum |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Tapetum nigrum |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Other findings |
N |
N |
N |
N |
N |
N |
N |
N |
G: Group; M: Male; F: Female; N: No abnormality detected; L: Left; R: Right.
TABLE 6 (Contd..,). SUMMARY OF OPHTHALMOSCOPIC EXAMINATION RECORD
Week 6 |
|||||||||||||||||||
Group & Sex |
G1R & M |
G4R & M |
G1R & F |
G4R & F |
|||||||||||||||
Dose (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
|||||||||||||||
No. of Animals |
5 |
5 |
5 |
5 |
|||||||||||||||
Observations |
|||||||||||||||||||
Eye Parameters ↓ |
L |
R |
L |
R |
L |
R |
L |
R |
|||||||||||
Adnexa |
Lids |
N |
N |
N |
N |
N |
N |
N |
N |
||||||||||
Ducts |
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 |
Vessels |
N |
N |
N |
N |
N |
N |
N |
N |
||||||||||
Macula |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Optic disc |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Tapetum lucidum |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Tapetum nigrum |
N |
N |
N |
N |
N |
N |
N |
N |
|||||||||||
Other findings |
N |
N |
N |
N |
N |
N |
N |
N |
G: Group; M: Male; F: Female; N: No abnormality detected; L: Left; R: Right
TABLE 7. SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB)RECORD
Parameters↓ |
|
Week 4 |
Week 6 |
|||||||||||||
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
G1R & M |
G4R & M |
||||||||||
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||||||||||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Home cage observations a. Convulsions |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
b. Tremors |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
c. Palpebral closure |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
Handling observation a. Ease of removal from the cage |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
b. Ease of handling animal in hand |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
c. Lacrimation |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
d. Red deposits around
|
Eyes |
1 |
1 |
1 |
1 |
1 |
1 |
|||||||||
Nose |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
Mouth |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
e. Crusty depositsaround
|
Eyes |
1 |
1 |
1 |
1 |
1 |
1 |
|||||||||
Nose |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
Mouth |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
f. Salivation |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
g. Fur appearance |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
h. Piloerection |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
i. Palpebral Closure |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
j. RespiratoryCharacter |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
k. EyeProminence |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
l. Muscle Tone |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
Home cage observations: a. Convulsions -1=Absentb. Tremors-1=Absentc. Palpebral closure -1=Normal, Handling observation : a. Ease of removal from the cage -2=Normal, b. Ease of handling animal in hand -2=Normal, c. Lacrimation -1=None, d. Red deposits around -1=Absente. Crusty deposits around -1=Absentf. Salivation-1=Normal, g. Fur Appearance -1=Normal, h. Piloerection -1=None, i. Palpebral Closure -1=Normal, j. Respiratory character -1=Normal, k. Eye Prominence -1=Normal, l. Muscle tone -1=Normal |
||||||||||||||||
G: Group; M: Male; R: Recovery;
TABLE 7 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Parameters↓ |
|
Week 4 |
Week 6 |
|||||||||||||
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
G1R & M |
G4R & M |
||||||||||
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
||||||||||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Open field Observation a. Mobility |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
b. Gait |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
c. Arousal |
3 |
3 |
3 |
3 |
3 |
3 |
||||||||||
d. Rearing |
Mean |
4.2 |
3.8 |
3.6 |
4.2 |
4.0 |
4.0 |
|||||||||
±SD |
0.8 |
0.8 |
0.9 |
0.8 |
0.7 |
0.7 |
||||||||||
e. Urination Numbers of pools of urine |
Mean |
2.4 |
2.4 |
2.0 |
2.4 |
1.6 |
1.4 |
|||||||||
±SD |
1.1 |
1.1 |
0.7 |
1.1 |
0.5 |
0.9 |
||||||||||
f. Defecation Number of fecal pellets |
Mean |
1.8 |
1.8 |
1.6 |
2.0 |
1.2 |
1.2 |
|||||||||
±SD |
0.4 |
0.4 |
0.5 |
0.7 |
0.8 |
0.8 |
||||||||||
g. Stereotypies- repetitive circling |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
h. Excessive grooming |
Mean |
2.6 |
2.4 |
2.4 |
2.6 |
3.2 |
3.4 |
|||||||||
±SD |
0.5 |
0.5 |
0.5 |
0.5 |
0.8 |
0.5 |
||||||||||
Sensory observations a.Startle response |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
b. Touch response |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
c. Pupil response |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
d. Response to nociceptive stimuli |
2 |
2 |
2 |
2 |
2 |
2 |
||||||||||
e. Righting reflex |
1 |
1 |
1 |
1 |
1 |
1 |
||||||||||
Physiological observation Body temperature (°F) |
Mean |
98.8 |
99.3 |
99.0 |
99.0 |
99.4 |
99.3 |
|||||||||
±SD |
0.6 |
0.4 |
0.6 |
0.6 |
0.7 |
0.4 |
||||||||||
Open field Observation: a. Mobility- 1=Normal,b. Gait- 1=Normal,c. Arousal- 3=Normal, g. Stereotypies- repetitive circling - 1=Absent,Sensory Observations: a. Startle Response-2=Normal,b. Touch Response- 2=Normal,c. Pupil Response2=Normal,d. Response to Nociceptive stimuli- 2=Normal, e. Righting Reflex- 1=Present |
||||||||||||||||
G: Group; M: Male; R: Recovery; Slight were perineum was noted in G4M (2/5) and G4F (2/5)
TABLE 7 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Parameters↓ |
|
Week 4 |
Week 6 |
|
|||||||||||||
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
G1R & F |
G4R & F |
|
||||||||||
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
|
||||||||||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
|
||||||||||
Home cage observations a. Convulsions |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
b. Tremors |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
c. Palpebral closure |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
Handling observation a. Ease of removal from the cage |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
b. Ease of handling animal in hand |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
c. Lacrimation |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
d. Red deposits around
|
Eyes |
1 |
1 |
1 |
1 |
1 |
1 |
|
|||||||||
Nose |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
Mouth |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
e. Crusty depositsaround
|
Eyes |
1 |
1 |
1 |
1 |
1 |
1 |
|
|||||||||
Nose |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
Mouth |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
f. Salivation |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
g. Fur appearance |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
h. Piloerection |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
i. Palpebral Closure |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
j. RespiratoryCharacter |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
k. EyeProminence |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
l. Muscle Tone |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
Home cage observations: a. Convulsions -1=Absentb. Tremors-1=Absentc. Palpebral closure -1=Normal, Handling observation : a. Ease of removal from the cage -2=Normal, b. Ease of handling animal in hand -2=Normal, c. Lacrimation -1=None, d. Red deposits around -1=Absente. Crusty deposits around -1=Absentf. Salivation-1=Normal, g. Fur Appearance -1=Normal, h. Piloerection -1=None, i. Palpebral Closure -1=Normal, j. Respiratory character -1=Normal, k. Eye Prominence -1=Normal, l. Muscle tone -1=Normal |
|||||||||||||||||
G: Group; F: Female; R: Recovery
TABLE 7 (Contd..,). SUMMARY OF NEUROLOGICAL/FUNCTIONAL OBSERVATION BATTERY (FOB) RECORD
Parameters↓ |
|
Week 4 |
Week 6 |
|
|||||||||||||
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
G1R & F |
G4R & F |
|
||||||||||
Dose (mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
|
||||||||||
Number of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
|
||||||||||
Open field Observation a. Mobility |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
b. Gait |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
c. Arousal |
3 |
3 |
3 |
3 |
3 |
3 |
|
||||||||||
d. Rearing |
Mean |
3.8 |
3.6 |
3.4 |
3.8 |
4.0 |
4.0 |
|
|||||||||
±SD |
0.8 |
0.5 |
0.5 |
0.8 |
0.7 |
0.7 |
|
||||||||||
e. Urination Numbers of pools of urine |
Mean |
1.6 |
2.0 |
1.8 |
1.6 |
1.4 |
1.4 |
|
|||||||||
±SD |
1.1 |
0.7 |
0.8 |
1.1 |
0.5 |
0.5 |
|
||||||||||
f. Defecation Number of fecal pellets |
Mean |
1.4 |
1.6 |
1.6 |
1.4 |
1.4 |
1.4 |
|
|||||||||
±SD |
0.9 |
0.5 |
0.5 |
0.9 |
0.5 |
0.5 |
|
||||||||||
g. Stereotypies- repetitive circling |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
h. Excessive grooming |
Mean |
2.6 |
2.8 |
2.6 |
2.4 |
2.8 |
3.0 |
|
|||||||||
±SD |
0.5 |
0.4 |
0.5 |
0.5 |
0.4 |
0.7 |
|
||||||||||
Sensory observations a.Startle response |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
b. Touch response |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
c. Pupil response |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
d. Response to nociceptive stimuli |
2 |
2 |
2 |
2 |
2 |
2 |
|
||||||||||
e. Righting reflex |
1 |
1 |
1 |
1 |
1 |
1 |
|
||||||||||
Physiological observation Body temperature (°F) |
Mean |
99.6 |
99.2 |
99.2 |
99.7 |
99.5 |
99.3 |
|
|||||||||
±SD |
0.7 |
0.9 |
0.8 |
0.5 |
0.8 |
0.7 |
|
||||||||||
Open field Observation: a. Mobility- 1=Normal,b. Gait- 1=Normal,c. Arousal- 3=Normal, g. Stereotypies- repetitive circling - 1=Absent,Sensory Observations: a. Startle Response-2=Normal,b. Touch Response- 2=Normal,c. Pupil Response2=Normal,d. Response to Nociceptive stimuli- 2=Normal, e. Righting Reflex- 1=Present |
|||||||||||||||||
G: Group; F: Female; R: Recovery
TABLE 8. SUMMARY OF LANDING FOOT SPLAY (cm) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Hind Limb Foot Splay (cm) |
||||
G1, M & 0 |
Mean |
6.1 |
|||
±SD |
0.4 |
||||
n |
5 |
||||
G2, M & 100 |
Mean |
6.1 |
|||
±SD |
0.3 |
||||
n |
5 |
||||
G3, M & 300 |
Mean |
6.4 |
|||
±SD |
0.3 |
||||
n |
5 |
||||
G4, M & 1000 |
Mean |
6.4 |
|||
±SD |
0.3 |
||||
n |
5 |
||||
G1, F & 0 |
Mean |
5.5 |
|||
±SD |
0.9 |
||||
n |
5 |
||||
G2, F & 100 |
Mean |
5.4 |
|||
±SD |
0.3 |
||||
n |
5 |
||||
G3, F & 300 |
Mean |
5.2 |
|||
±SD |
0.2 |
||||
n |
5 |
||||
G4, F & 1000 |
Mean |
5.2 |
|||
±SD |
0.3 |
||||
n |
5 |
||||
G1R, M & 0 |
Mean |
6.6 |
|||
±SD |
0.8 |
||||
n |
5 |
||||
G4R, M & 1000 |
Mean |
6.5 |
|||
±SD |
0.5 |
||||
n |
5 |
||||
G1R, F & 0 |
Mean |
5.3 |
|||
±SD |
0.8 |
||||
n |
5 |
||||
G4R, F & 1000 |
Mean |
5.4 |
|||
±SD |
0.5 |
||||
n |
5 |
G: Group; M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals
TABLE 9. SUMMARY OF PHOTOACTOMETER READING RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Movement counts |
||||
G1, M & 0 |
Mean |
619.2 |
|||
±SD |
41.6 |
||||
n |
5 |
||||
G2, M & 100 |
Mean |
603.6 |
|||
±SD |
22.9 |
||||
n |
5 |
||||
G3, M & 300 |
Mean |
561.6 |
|||
±SD |
91.1 |
||||
n |
5 |
||||
G4, M & 1000 |
Mean |
523.0* |
|||
±SD |
52.2 |
||||
n |
5 |
||||
G1, F & 0 |
Mean |
665.6 |
|||
±SD |
35.4 |
||||
n |
5 |
||||
G2, F & 100 |
Mean |
600.4 |
|||
±SD |
45.7 |
||||
n |
5 |
||||
G3, F & 300 |
Mean |
625.6 |
|||
±SD |
55.6 |
||||
n |
5 |
||||
G4, F & 1000 |
Mean |
584.6 |
|||
±SD |
70.9 |
||||
n |
5 |
||||
G1R, M & 0 |
Mean |
653.4 |
|||
±SD |
50.4 |
||||
n |
5 |
||||
G4R, M & 1000 |
Mean |
580.8 |
|||
±SD |
66.9 |
||||
n |
5 |
||||
G1R, F & 0 |
Mean |
711.4 |
|||
±SD |
55.0 |
||||
n |
5 |
||||
G4R, F & 1000 |
Mean |
697.8 |
|||
±SD |
43.1 |
||||
n |
5 |
G: Group; M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals;
*: Statistically significant (p<0.05)
TABLE 10.SUMMARY OF GRIP STRENGTH (kgf) MEASUREMENT RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fore limb |
Hind limb |
|||||
G1, M & 0 |
Mean |
1.511 |
0.526 |
||||
±SD |
0.041 |
0.027 |
|||||
n |
5 |
5 |
|||||
G2, M & 100 |
Mean |
1.525 |
0.518 |
||||
±SD |
0.040 |
0.025 |
|||||
n |
5 |
5 |
|||||
G3, M & 300 |
Mean |
1.523 |
0.529 |
||||
±SD |
0.040 |
0.020 |
|||||
n |
5 |
5 |
|||||
G4, M & 1000 |
Mean |
1.507 |
0.516 |
||||
±SD |
0.032 |
0.037 |
|||||
n |
5 |
5 |
|||||
G1, F & 0 |
Mean |
1.518 |
0.510 |
||||
±SD |
0.023 |
0.040 |
|||||
n |
5 |
5 |
|||||
G2, F & 100 |
Mean |
1.531 |
0.536 |
||||
±SD |
0.024 |
0.025 |
|||||
n |
5 |
5 |
|||||
G3, F & 300 |
Mean |
1.541 |
0.550 |
||||
±SD |
0.024 |
0.020 |
|||||
n |
5 |
5 |
|||||
G4, F & 1000 |
Mean |
1.516 |
0.502 |
||||
±SD |
0.015 |
0.039 |
|||||
n |
5 |
5 |
|||||
G1R, M & 0 |
Mean |
1.493 |
0.506 |
||||
±SD |
0.016 |
0.053 |
|||||
n |
5 |
5 |
|||||
G4R, M & 1000 |
Mean |
1.487 |
0.505 |
||||
±SD |
0.019 |
0.043 |
|||||
n |
5 |
5 |
|||||
G1R, F & 0 |
Mean |
1.483 |
0.489 |
||||
±SD |
0.034 |
0.042 |
|||||
n |
5 |
5 |
|||||
G4R, F & 1000 |
Mean |
1.478 |
0.481 |
||||
±SD |
0.026 |
0.053 |
|||||
n |
5 |
5 |
G: Group; M: Male; F: Female; R: Recovery; SD: Standard Deviation; n: number of animals.
TABLE 11. SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Hemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Hemoglobin |
Mean Corpuscular Hemoglobin 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 |
8.88 |
7.15 |
13.72 |
42.30 |
59.22 |
19.20 |
32.40 |
917.60 |
7.44 |
|||||||||||
±SD |
3.00 |
0.38 |
0.54 |
1.48 |
1.70 |
0.56 |
0.24 |
215.31 |
0.53 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G2, M & 100 |
Mean |
8.85 |
7.41 |
13.96 |
43.18 |
58.32 |
18.88 |
32.38 |
890.40 |
7.54 |
|||||||||||
±SD |
3.67 |
0.40 |
0.68 |
1.98 |
1.52 |
0.39 |
0.45 |
66.20 |
0.17 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G3, M & 300 |
Mean |
10.74 |
7.35 |
13.18 |
41.56 |
56.86 |
18.08 |
31.68 |
916.00 |
8.58 |
|||||||||||
±SD |
1.72 |
0.48 |
1.76 |
3.05 |
6.98 |
3.05 |
2.16 |
290.00 |
1.60 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4, M & 1000 |
Mean |
10.86 |
6.94 |
12.36 |
40.60 |
58.58 |
17.72 |
30.30 |
882.20 |
8.02 |
|||||||||||
±SD |
2.93 |
0.33 |
2.43 |
1.50 |
1.12 |
3.22 |
5.56 |
101.56 |
0.55 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G1R, M & 0 |
Mean |
10.64 |
7.10 |
13.42 |
40.18 |
56.74 |
18.98 |
33.42 |
983.20 |
7.56 |
|||||||||||
±SD |
2.48 |
0.59 |
0.73 |
2.12 |
2.13 |
1.30 |
1.22 |
110.08 |
0.21 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4R, M & 1000 |
Mean |
9.93 |
6.85 |
13.28 |
39.48 |
57.66 |
19.40 |
33.60 |
1007.40 |
7.64 |
|||||||||||
±SD |
1.56 |
0.15 |
0.26 |
0.73 |
0.29 |
0.30 |
0.51 |
68.20 |
0.38 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n:number of animals.
TABLE 11 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Reticulocyte Count |
||||||||||
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Retic) |
|||||||||||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(109cells/L) |
|||||||||||
G1, M & 0 |
Mean |
1.86 |
21.46 |
73.04 |
3.16 |
0.78 |
0.58 |
133.36 |
|||||||||
±SD |
0.52 |
4.08 |
4.68 |
0.58 |
0.30 |
0.13 |
38.89 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, M & 100 |
Mean |
1.66 |
22.36 |
72.26 |
3.22 |
0.56 |
0.54 |
122.72 |
|||||||||
±SD |
0.30 |
4.44 |
4.17 |
0.27 |
0.15 |
0.11 |
21.50 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, M & 300 |
Mean |
2.11 |
19.40 |
72.80 |
4.78* |
1.16 |
0.48 |
156.70 |
|||||||||
±SD |
0.66 |
2.28 |
3.53 |
1.29 |
0.45 |
0.15 |
56.89 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, M & 1000 |
Mean |
1.43 |
35.58* |
57.80* |
4.00 |
0.52 |
0.48 |
98.70 |
|||||||||
±SD |
0.39 |
10.83 |
9.60 |
0.92 |
0.28 |
0.25 |
23.42 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, M & 0 |
Mean |
2.04 |
23.58 |
72.16 |
2.06 |
0.62 |
0.48 |
145.42 |
|||||||||
±SD |
0.27 |
7.88 |
8.27 |
0.63 |
0.08 |
0.16 |
29.01 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, M & 1000 |
Mean |
1.97 |
17.08 |
78.26 |
2.64 |
0.66 |
0.44 |
135.14 |
|||||||||
±SD |
0.22 |
0.61 |
1.09 |
0.55 |
0.24 |
0.05 |
13.87 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G:
Group; M: Male; R: Recovery; SD: Standard Deviation; n:number
of animals;
*: Statistically significant (p<0.05)
TABLE 11 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
||||||||||
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
|||||||||||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
|||||||||||
G1, M & 0 |
Mean |
1.87 |
6.52 |
0.28 |
0.07 |
0.06 |
20.78 |
25.86 |
|||||||||
±SD |
0.68 |
2.28 |
0.10 |
0.04 |
0.02 |
2.59 |
2.40 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, M & 100 |
Mean |
1.93 |
6.44 |
0.29 |
0.05 |
0.05 |
18.72 |
23.72 |
|||||||||
±SD |
0.79 |
2.80 |
0.11 |
0.02 |
0.02 |
1.12 |
3.61 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, M & 300 |
Mean |
2.08 |
7.80 |
0.53* |
0.12 |
0.06 |
17.58 |
25.48 |
|||||||||
±SD |
0.39 |
1.23 |
0.21 |
0.05 |
0.02 |
2.95 |
3.46 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, M & 1000 |
Mean |
4.10* |
6.07 |
0.43 |
0.05 |
0.05 |
18.66 |
23.20 |
|||||||||
±SD |
2.47 |
0.77 |
0.12 |
0.02 |
0.02 |
1.90 |
3.39 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, M & 0 |
Mean |
2.65 |
7.52 |
0.23 |
0.07 |
0.05 |
33.00 |
26.68 |
|||||||||
±SD |
1.66 |
0.79 |
0.12 |
0.02 |
0.02 |
18.75 |
7.74 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, M & 1000 |
Mean |
1.70 |
7.76 |
0.27 |
0.06 |
0.04 |
20.86 |
31.50 |
|||||||||
±SD |
0.28 |
1.20 |
0.09 |
0.02 |
0.01 |
2.23 |
3.22 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n:number of animals; *: Statistically significant (p<0.05)
TABLE 11 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Total Leucocyte Count |
Total Erythrocyte Count |
Hemoglobin |
Haematocrit |
Mean Corpuscular Volume |
Mean Corpuscular Hemoglobin |
Mean Corpuscular Hemoglobin 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 |
8.82 |
6.90 |
13.46 |
40.78 |
59.12 |
19.50 |
33.00 |
905.80 |
7.56 |
|||||||||||
±SD |
3.75 |
0.25 |
0.51 |
1.11 |
1.18 |
0.19 |
0.51 |
165.01 |
0.05 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G2, F & 100 |
Mean |
9.03 |
6.73 |
13.38 |
40.14 |
59.74 |
19.94 |
33.40 |
889.80 |
7.86 |
|||||||||||
±SD |
1.51 |
0.34 |
0.70 |
1.69 |
1.32 |
0.22 |
0.58 |
98.85 |
0.36 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G3, F & 300 |
Mean |
8.76 |
6.42 |
12.38 |
38.48 |
60.04 |
19.30 |
32.14 |
941.20 |
7.76 |
|||||||||||
±SD |
4.34 |
0.40 |
0.80 |
1.41 |
1.80 |
0.51 |
1.31 |
186.29 |
0.21 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4, F & 1000 |
Mean |
12.08 |
7.06 |
13.50 |
41.38 |
58.70 |
19.14 |
32.60 |
1020.80 |
7.96 |
|||||||||||
±SD |
3.28 |
0.72 |
1.06 |
3.45 |
1.25 |
0.49 |
0.27 |
145.92 |
0.47 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G1R, F & 0 |
Mean |
8.76 |
6.81 |
13.10 |
38.36 |
56.42 |
19.28 |
34.14 |
914.80 |
7.32 |
|||||||||||
±SD |
3.15 |
0.30 |
0.28 |
1.11 |
1.24 |
0.83 |
0.70 |
138.18 |
0.19 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4R, F & 1000 |
Mean |
9.69 |
6.74 |
13.80* |
39.34 |
58.34 |
20.50* |
35.18* |
1033.20 |
7.20 |
|||||||||||
±SD |
1.64 |
0.18 |
0.34 |
1.05 |
2.03 |
0.72 |
0.18 |
83.29 |
0.12 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 11 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Reticulocyte Count |
Neutrophils |
Lymphocytes |
Monocytes |
Eosinophils |
Basophils |
Absolute Reticulocyte Count |
||||||||||
(Retic) |
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(Retic) |
|||||||||||
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(109cells/L) |
|||||||||||
G1, F & 0 |
Mean |
1.61 |
19.76 |
75.22 |
2.46 |
0.84 |
0.46 |
110.56 |
|||||||||
±SD |
0.31 |
2.55 |
1.87 |
0.61 |
0.35 |
0.13 |
20.46 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 100 |
Mean |
1.58 |
24.28 |
70.00 |
3.40 |
0.56 |
0.42 |
106.28 |
|||||||||
±SD |
0.57 |
9.05 |
9.06 |
0.89 |
0.25 |
0.19 |
38.40 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 300 |
Mean |
1.22 |
21.50 |
73.50 |
2.48 |
0.88 |
0.38 |
78.84 |
|||||||||
±SD |
0.41 |
6.95 |
7.64 |
0.80 |
0.64 |
0.25 |
29.53 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 1000 |
Mean |
1.71 |
35.84* |
56.92* |
5.20* |
0.52 |
0.48 |
120.26 |
|||||||||
±SD |
0.52 |
8.33 |
9.49 |
1.89 |
0.08 |
0.16 |
36.41 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, F & 0 |
Mean |
1.65 |
18.14 |
76.88 |
2.48 |
0.98 |
0.44 |
111.38 |
|||||||||
±SD |
0.47 |
4.38 |
5.31 |
0.65 |
0.24 |
0.11 |
30.61 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 1000 |
Mean |
1.89 |
21.12 |
73.92 |
2.56 |
1.02 |
0.44 |
126.46 |
|||||||||
±SD |
1.01 |
5.07 |
5.53 |
0.65 |
0.26 |
0.09 |
65.74 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals; *: Statistically significant (p<0.05)
TABLE 11 (Contd..,). SUMMARY OF HAEMATOLOGY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Absolute Neutrophils |
Absolute Lymphocytes |
Absolute Monocytes |
Absolute Eosinophils |
Absolute Basophils |
Prothrombin Time |
Activated Prothrombin Time |
||||||||||
(Neut) |
(Lymph) |
(Mono) |
(Eos) |
(Baso) |
(PT) |
(APTT) |
|||||||||||
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(103cells/µL) |
(Seconds) |
(Seconds) |
|||||||||||
G1, F & 0 |
Mean |
1.72 |
6.65 |
0.22 |
0.07 |
0.05 |
19.28 |
23.44 |
|||||||||
±SD |
0.76 |
2.88 |
0.09 |
0.06 |
0.03 |
1.81 |
2.31 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G2, F & 100 |
Mean |
2.19 |
6.32 |
0.31 |
0.05 |
0.04 |
18.70 |
19.72 |
|||||||||
±SD |
0.86 |
1.36 |
0.10 |
0.03 |
0.02 |
0.53 |
1.77 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G3, F & 300 |
Mean |
1.69 |
6.66 |
0.20 |
0.06 |
0.04 |
19.94 |
26.46 |
|||||||||
±SD |
0.57 |
4.03 |
0.07 |
0.03 |
0.05 |
3.60 |
5.13 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4, F & 1000 |
Mean |
4.44* |
6.74 |
0.65* |
0.06 |
0.06 |
18.46 |
26.38 |
|||||||||
±SD |
1.83 |
1.61 |
0.37 |
0.02 |
0.02 |
1.68 |
2.67 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G1R, F & 0 |
Mean |
1.50 |
6.84 |
0.21 |
0.08 |
0.04 |
19.68 |
28.84 |
|||||||||
±SD |
0.28 |
2.83 |
0.05 |
0.03 |
0.01 |
3.05 |
5.11 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
G4R, F & 1000 |
Mean |
2.02 |
7.20 |
0.24 |
0.10 |
0.04 |
27.44 |
21.28 |
|||||||||
±SD |
0.47 |
1.57 |
0.03 |
0.04 |
0.02 |
7.74 |
6.50 |
||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 12. SUMMARY OF CLINICAL CHEMISTRYRECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Bilirubin |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
|||||||||||||
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(BIT) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
|||||||||||||||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
||||||||||||||
G1, M & 0 |
Mean |
78.00 |
28.22 |
0.48 |
53.40 |
54.40 |
0.06 |
5.86 |
3.21 |
48.60 |
100.80 |
||||||||||||
±SD |
29.83 |
1.79 |
0.03 |
5.86 |
12.76 |
0.02 |
0.21 |
0.20 |
8.23 |
8.38 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, M & 100 |
Mean |
72.40 |
21.92* |
0.47 |
42.40 |
55.00 |
0.05 |
6.16 |
3.25 |
50.20 |
105.40 |
||||||||||||
±SD |
8.79 |
3.56 |
0.03 |
14.31 |
8.75 |
0.03 |
0.46 |
0.20 |
8.14 |
7.60 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, M & 300 |
Mean |
52.80 |
21.54* |
0.44* |
49.60 |
60.80 |
0.04 |
5.98 |
3.10 |
55.60 |
112.60 |
||||||||||||
±SD |
9.52 |
3.25 |
0.01 |
7.57 |
16.77 |
0.03 |
0.30 |
0.10 |
7.44 |
18.28 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, M & 1000 |
Mean |
59.40 |
28.28 |
0.45 |
35.80* |
54.60 |
0.09 |
5.66 |
3.11 |
68.00 |
136.60* |
||||||||||||
±SD |
7.02 |
3.50 |
0.02 |
5.17 |
21.36 |
0.01 |
0.38 |
0.14 |
24.11 |
22.22 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, M & 0 |
Mean |
90.20 |
27.82 |
0.60 |
44.80 |
44.20 |
0.02 |
6.50 |
3.17 |
42.40 |
75.40 |
||||||||||||
±SD |
7.19 |
2.53 |
0.05 |
9.09 |
5.97 |
0.00 |
0.14 |
0.09 |
1.95 |
9.91 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, M & 1000 |
Mean |
88.60 |
28.86 |
0.60 |
49.40 |
51.60 |
0.03 |
6.48 |
3.16 |
45.40 |
86.00 |
||||||||||||
±SD |
10.01 |
2.13 |
0.02 |
7.92 |
11.28 |
0.01 |
0.32 |
0.10 |
7.23 |
8.89 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 12 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alkaline phosphatase |
Calcium |
Phosphorous |
Cholinesterase |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|||||||||||||
(ALP) |
(CAL) |
(PHO) |
(CHE) |
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||||||||||||||
(U/L) |
(mg/dL) |
(mg/dL) |
(U/L) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||||||||||||||
G1, M & 0 |
Mean |
192.80 |
9.70 |
7.72 |
120.40 |
2.65 |
1.21 |
13.17 |
145.46 |
3.60 |
107.20 |
||||||||||||
±SD |
27.47 |
0.29 |
1.13 |
33.59 |
0.10 |
0.09 |
0.83 |
0.96 |
0.56 |
0.85 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, M & 100 |
Mean |
300.80 |
9.62 |
7.62 |
124.00 |
2.91 |
1.12 |
10.23* |
147.06 |
3.36 |
107.80 |
||||||||||||
±SD |
121.48 |
0.28 |
0.13 |
25.72 |
0.27 |
0.06 |
1.66 |
1.90 |
0.14 |
1.73 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, M & 300 |
Mean |
409.00* |
9.50 |
8.42 |
107.60 |
2.88 |
1.08* |
10.05* |
146.90 |
3.69 |
108.28 |
||||||||||||
±SD |
90.27 |
0.12 |
0.64 |
26.67 |
0.23 |
0.06 |
1.52 |
1.18 |
0.27 |
1.89 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, M & 1000 |
Mean |
229.80 |
8.94* |
7.46 |
136.40 |
2.55 |
1.23 |
13.20 |
147.30 |
3.46 |
109.52 |
||||||||||||
±SD |
81.87 |
0.52 |
0.76 |
39.82 |
0.25 |
0.08 |
1.63 |
1.92 |
0.39 |
2.14 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, M & 0 |
Mean |
149.60 |
10.02 |
6.96 |
173.80 |
3.33 |
0.96 |
12.98 |
142.24 |
3.34 |
106.58 |
||||||||||||
±SD |
37.75 |
0.18 |
0.23 |
18.32 |
0.16 |
0.06 |
1.18 |
1.19 |
0.33 |
0.90 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, M & 1000 |
Mean |
168.40 |
9.90 |
7.32 |
167.00 |
3.32 |
0.96 |
13.47 |
142.68 |
3.44 |
106.72 |
||||||||||||
±SD |
30.36 |
0.14 |
0.28 |
20.92 |
0.26 |
0.07 |
0.99 |
0.95 |
0.52 |
1.62 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 12 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Glucose |
Urea |
Creatinine |
Total Cholesterol |
Triglycerides |
Total Bilirubin |
Total Protein |
Albumin |
Alanine aminotransferase |
Aspartate aminotransferase |
|||||||||||||
(GLU) |
(CRE) |
(CHO) |
(TRI) |
(BIT) |
(TPR) |
(ALB) |
(ALT) |
(AST) |
|||||||||||||||
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(g/dL) |
(g/dL) |
(U/L) |
(U/L) |
||||||||||||||
G1, F & 0 |
Mean |
72.60 |
26.48 |
0.50 |
55.20 |
41.20 |
0.06 |
6.40 |
3.33 |
37.40 |
104.20 |
||||||||||||
±SD |
11.93 |
2.64 |
0.02 |
4.71 |
4.15 |
0.01 |
0.32 |
0.20 |
6.07 |
15.43 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, F & 100 |
Mean |
80.80 |
23.94 |
0.49 |
56.20 |
39.40 |
0.07 |
6.52 |
3.38 |
46.40 |
101.60 |
||||||||||||
±SD |
21.43 |
4.09 |
0.02 |
7.53 |
8.50 |
0.02 |
0.18 |
0.11 |
5.86 |
12.60 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, F & 300 |
Mean |
63.20 |
25.76 |
0.49 |
48.20 |
39.60 |
0.09 |
6.28 |
3.38 |
50.20 |
104.20 |
||||||||||||
±SD |
12.07 |
2.66 |
0.03 |
12.30 |
7.50 |
0.02 |
0.34 |
0.19 |
11.65 |
15.67 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, F & 1000 |
Mean |
62.80 |
27.80 |
0.49 |
26.20* |
35.80 |
0.13* |
5.82* |
3.19 |
59.60* |
123.00 |
||||||||||||
±SD |
7.53 |
4.18 |
0.05 |
4.97 |
6.91 |
0.04 |
0.39 |
0.25 |
17.81 |
10.20 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, F & 0 |
Mean |
100.40 |
35.60 |
0.70 |
63.40 |
43.00 |
0.02 |
7.06 |
3.57 |
34.00 |
74.60 |
||||||||||||
±SD |
11.24 |
3.43 |
0.03 |
10.67 |
4.00 |
0.01 |
0.30 |
0.18 |
2.55 |
6.35 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, F & 1000 |
Mean |
112.00 |
38.52 |
0.67 |
53.60 |
44.80 |
0.02 |
7.02 |
3.46 |
36.20 |
74.20 |
||||||||||||
±SD |
22.51 |
4.71 |
0.05 |
9.56 |
15.17 |
0.00 |
0.33 |
0.26 |
7.05 |
10.69 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 12 (Contd..,). SUMMARY OF CLINICAL CHEMISTRY RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Alkaline phosphatase |
Calcium |
Phosphorous |
Cholinesterase |
Globulin |
Albumin/Globulin ratio |
Blood Urea Nitrogen |
Sodium |
Potassium |
Chloride |
|||||||||||||
(ALP) |
(CAL) |
(PHO) |
(CHE) |
(GLO) |
(A/G Ratio) |
(BUN) |
(Na) |
(K) |
(CLO) |
||||||||||||||
(U/L) |
(mg/dL) |
(mg/dL) |
(U/L) |
(g/dL) |
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
|||||||||||||||
G1, F & 0 |
Mean |
90.80 |
9.64 |
6.72 |
584.80 |
3.07 |
1.09 |
12.36 |
147.58 |
3.21 |
109.32 |
||||||||||||
±SD |
14.52 |
0.15 |
0.63 |
113.06 |
0.21 |
0.08 |
1.24 |
1.10 |
0.32 |
1.39 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, F & 100 |
Mean |
155.60* |
9.80 |
7.04 |
420.00 |
3.14 |
1.08 |
11.17 |
147.62 |
3.31 |
108.40 |
||||||||||||
±SD |
24.54 |
0.42 |
1.19 |
98.38 |
0.19 |
0.09 |
1.91 |
1.19 |
0.35 |
1.37 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, F & 300 |
Mean |
201.20* |
9.46 |
6.84 |
489.00 |
2.90 |
1.16 |
12.02 |
147.36 |
3.12 |
107.94 |
||||||||||||
±SD |
39.75 |
0.42 |
0.47 |
114.72 |
0.16 |
0.04 |
1.24 |
0.93 |
0.26 |
1.82 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, F & 1000 |
Mean |
191.00* |
9.20 |
6.40 |
293.60* |
2.63* |
1.21 |
12.97 |
145.62 |
3.16 |
107.96 |
||||||||||||
±SD |
40.32 |
0.25 |
0.54 |
158.83 |
0.23 |
0.12 |
1.95 |
1.95 |
0.39 |
2.37 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, F & 0 |
Mean |
88.40 |
10.16 |
6.06 |
746.00 |
3.49 |
1.02 |
16.61 |
142.98 |
3.31 |
107.54 |
||||||||||||
±SD |
26.50 |
0.23 |
0.45 |
147.97 |
0.14 |
0.03 |
1.60 |
0.83 |
0.08 |
0.59 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, F & 1000 |
Mean |
101.40 |
10.02 |
6.14 |
607.80 |
3.56 |
0.97 |
17.98 |
142.82 |
3.63 |
106.44 |
||||||||||||
±SD |
24.93 |
0.40 |
0.30 |
414.52 |
0.12 |
0.07 |
2.20 |
0.79 |
0.50 |
0.92 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 13. SUMMARY OF URINE ANALYSIS RECORD
|
Group & Sex |
G1 & M |
G2 & M |
G3 & M |
G4 & M |
G1R & M |
G4R & M |
||||||||||
Dose(mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
|||||||||||
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||
Physical |
Colour |
Pale Yellow |
2 |
4 |
4 |
5 |
4 |
5 |
|||||||||
Yellow |
3 |
1 |
1 |
- |
1 |
- |
|||||||||||
Appearance |
Clear |
3 |
3 |
4 |
5 |
4 |
5 |
||||||||||
Turbid |
2 |
2 |
1 |
- |
1 |
- |
|||||||||||
Volume (mL) |
Mean ±SD |
6.4 |
6.2 |
5.7 |
6.0 |
5.4 |
5.8 |
||||||||||
1.5 |
0.9 |
1.0 |
1.4 |
0.4 |
0.9 |
||||||||||||
Chemical |
pH |
Mean ±SD |
8.0 |
7.0 |
7.1 |
7.2 |
8.2 |
8.0 |
|||||||||
0.7 |
0.5 |
0.5 |
0.8 |
0.3 |
0.5 |
||||||||||||
Specific gravity |
Mean ±SD |
1.011 |
1.011 |
1.014 |
1.010 |
1.010 |
1.009 |
||||||||||
0.005 |
0.005 |
0.009 |
0.000 |
0.000 |
0.002 |
||||||||||||
Urobilinogen (mg/dL) |
Mean ±SD |
0.4 |
0.2 |
0.2 |
0.2 |
0.2 |
0.2 |
||||||||||
0.4 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
||||||||||||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Ketones (mg/dL) |
5 |
3 |
3 |
1 |
2 |
5 |
- |
||||||||||
Neg |
2 |
2 |
4 |
3 |
- |
5 |
|||||||||||
Blood (Ery/µL)
|
Neg |
3 |
- |
2 |
- |
1 |
5 |
||||||||||
Ca10 |
1 |
1 |
1 |
2 |
- |
- |
|||||||||||
Ca25 |
1 |
4 |
2 |
3 |
3 |
- |
|||||||||||
Ca80 |
- |
- |
- |
- |
1 |
- |
|||||||||||
Proteins (mg/dL) |
Trace |
1 |
1 |
3 |
2 |
4 |
1 |
||||||||||
Neg |
1 |
2 |
1 |
3 |
- |
4 |
|||||||||||
30 |
1 |
2 |
1 |
- |
- |
- |
|||||||||||
100 |
1 |
- |
- |
- |
1 |
- |
|||||||||||
>=300 |
1 |
- |
- |
- |
- |
- |
|||||||||||
Nitrite |
Neg |
4 |
5 |
1 |
3 |
5 |
5 |
||||||||||
Pos |
1 |
- |
4 |
2 |
- |
- |
|||||||||||
Leucocytes (Leu/µL) |
Neg |
3 |
5 |
5 |
5 |
4 |
4 |
||||||||||
Ca15 |
2 |
- |
- |
- |
1 |
1 |
|||||||||||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Microscopic |
Epithelial cells |
0 |
4 |
4 |
3 |
4 |
3 |
3 |
|||||||||
0-1 |
1 |
- |
2 |
1 |
1 |
1 |
|||||||||||
1-2 |
- |
1 |
- |
- |
1 |
1 |
|||||||||||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; Ca: Calculated approximately; SD: Standard Deviation;
-: No observations noted;
TABLE 13 (Contd..,). SUMMARY OF URINE ANALYSIS RECORD
|
Group & Sex |
G1 & F |
G2 & F |
G3 & F |
G4 & F |
G1R & F |
G4R & F |
||||||||||
Dose(mg/kg body weight/day) |
0 |
100 |
300 |
1000 |
0 |
1000 |
|||||||||||
Number of animals |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||
Physical |
Colour |
Pale Yellow |
3 |
5 |
- |
3 |
2 |
3 |
|||||||||
Yellow |
2 |
- |
5 |
2 |
3 |
2 |
|||||||||||
Appearance |
Clear |
4 |
4 |
2 |
3 |
2 |
3 |
||||||||||
Turbid |
1 |
1 |
3 |
2 |
3 |
2 |
|||||||||||
Volume (mL) |
Mean ±SD |
5.9 |
6.2 |
6.5 |
5.6 |
5.6 |
5.3 |
||||||||||
1.9 |
1.2 |
1.1 |
1.5 |
1.2 |
1.1 |
||||||||||||
Chemical |
pH |
Mean ±SD |
7.9 |
8.1 |
7.1 |
7.8 |
8.5 |
8.5 |
|||||||||
0.4 |
0.2 |
0.9 |
0.8 |
0.0 |
0.0 |
||||||||||||
Specific gravity |
Mean ±SD |
1.011 |
1.008 |
1.018 |
1.012 |
1.006 |
1.009 |
||||||||||
0.007 |
0.003 |
0.010 |
0.008 |
0.002 |
0.004 |
||||||||||||
Urobilinogen (mg/dL) |
Mean ±SD |
0.2 |
0.2 |
0.2 |
0.2 |
0.5 |
0.2 |
||||||||||
0.0 |
0.0 |
0.0 |
0.0 |
0.4 |
0.0 |
||||||||||||
Bilirubin (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Ketones (mg/dL) |
5 |
- |
- |
4 |
1 |
4 |
5 |
||||||||||
Neg |
5 |
5 |
1 |
4 |
1 |
- |
|||||||||||
Blood (Ery/µL)
|
Neg |
2 |
1 |
3 |
4 |
5 |
3 |
||||||||||
Ca10 |
- |
1 |
1 |
1 |
- |
1 |
|||||||||||
Ca25 |
3 |
3 |
1 |
- |
- |
1 |
|||||||||||
Proteins (mg/dL) |
Trace |
3 |
5 |
- |
3 |
- |
1 |
||||||||||
30 |
1 |
- |
4 |
2 |
2 |
1 |
|||||||||||
100 |
1 |
- |
1 |
- |
- |
3 |
|||||||||||
>=300 |
- |
- |
- |
- |
3 |
- |
|||||||||||
Nitrite |
Neg |
3 |
3 |
1 |
2 |
1 |
5 |
||||||||||
Pos |
2 |
2 |
4 |
3 |
4 |
- |
|||||||||||
Leucocytes (Leu/µL) |
Neg |
4 |
5 |
4 |
5 |
- |
2 |
||||||||||
Ca15 |
1 |
- |
1 |
- |
3 |
2 |
|||||||||||
Ca70 |
- |
- |
- |
- |
- |
1 |
|||||||||||
Ca125 |
- |
- |
- |
- |
2 |
- |
|||||||||||
Glucose (mg/dL) |
Neg |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Microscopic |
Epithelial cells |
0 |
2 |
4 |
2 |
2 |
3 |
3 |
|||||||||
0-1 |
2 |
1 |
1 |
2 |
1 |
1 |
|||||||||||
1-2 |
1 |
- |
1 |
1 |
- |
1 |
|||||||||||
2-3 |
- |
- |
1 |
- |
1 |
- |
|||||||||||
Casts |
Absent |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||
Crystals |
Present |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; Ca: Calculated approximately; SD: Standard Deviation;
-: No observations noted.
TABLE 14. SUMMARY OF ABSOLUTE ORGAN WEIGHT (g)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Epididymis |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
|||||||||||||
G1, M & 0 |
Mean |
0.0632 |
0.3659 |
0.4042 |
1.0439 |
2.7126 |
0.8938 |
2.0984 |
1.8804 |
7.9667 |
1.6624 |
||||||||||||
±SD |
0.0155 |
0.0929 |
0.0493 |
0.0149 |
0.1284 |
0.0321 |
0.0489 |
0.0680 |
0.5287 |
0.2292 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, M & 100 |
Mean |
0.0653 |
0.4366 |
0.5396* |
1.1197 |
2.6714 |
1.0447* |
2.5895* |
1.9089 |
10.4089* |
1.8938 |
||||||||||||
±SD |
0.0093 |
0.0707 |
0.1257 |
0.0585 |
0.2764 |
0.0886 |
0.2819 |
0.0777 |
1.8151 |
0.0731 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, M & 300 |
Mean |
0.0650 |
0.5026 |
0.5181 |
1.1774* |
3.0695* |
1.1089* |
2.9429* |
2.0547 |
11.0130* |
2.3908* |
||||||||||||
±SD |
0.0095 |
0.0592 |
0.0359 |
0.0743 |
0.1480 |
0.0819 |
0.0495 |
0.2537 |
0.5488 |
0.5153 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, M & 1000 |
Mean |
0.0557 |
0.3316 |
0.4204 |
1.0225 |
2.8182 |
0.8916 |
2.2137 |
1.8334 |
9.6882 |
1.7699 |
||||||||||||
±SD |
0.0053 |
0.1217 |
0.0302 |
0.0683 |
0.1642 |
0.0402 |
0.2962 |
0.0606 |
1.5450 |
0.3296 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, M & 0 |
Mean |
0.0467 |
0.3566 |
0.4846 |
1.2428 |
2.8844 |
1.1545 |
2.3934 |
1.9366 |
9.6305 |
2.8592 |
||||||||||||
±SD |
0.0037 |
0.1127 |
0.0726 |
0.0746 |
0.1545 |
0.0923 |
0.3351 |
0.0947 |
0.8507 |
0.3037 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, M & 1000 |
Mean |
0.0569 |
0.3963 |
0.5472 |
1.2226 |
3.0443 |
1.2380 |
2.7301 |
2.0031 |
10.0676 |
2.7223 |
||||||||||||
±SD |
0.0098 |
0.0409 |
0.0790 |
0.0690 |
0.0783 |
0.0834 |
0.4558 |
0.0691 |
1.0711 |
0.2980 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; M: Male; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 14 (Contd..,). SUMMARY OF ABSOLUTE ORGAN WEIGHT (g) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
||||||||||||
G1, F & 0 |
Mean |
0.0687 |
0.4911 |
0.4541 |
0.4964 |
0.1554 |
0.8303 |
1.7937 |
1.8833 |
7.4558 |
|||||||||||
±SD |
0.0077 |
0.0901 |
0.0832 |
0.1060 |
0.0191 |
0.1074 |
0.3057 |
0.0928 |
1.3075 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G2, F & 100 |
Mean |
0.0802 |
0.4696 |
0.4551 |
0.5508 |
0.1450 |
0.8371 |
1.7849 |
1.7964 |
7.9453 |
|||||||||||
±SD |
0.0080 |
0.0815 |
0.0193 |
0.1484 |
0.0260 |
0.0593 |
0.1003 |
0.1504 |
0.1984 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G3, F & 300 |
Mean |
0.0689 |
0.4435 |
0.4854 |
0.5317 |
0.1554 |
0.8306 |
1.9649 |
1.9528 |
8.6017 |
|||||||||||
±SD |
0.0101 |
0.1219 |
0.0949 |
0.1248 |
0.0197 |
0.0454 |
0.0877 |
0.0634 |
0.4803 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4, F & 1000 |
Mean |
0.0803 |
0.5359 |
0.5362 |
0.5131 |
0.1453 |
0.8156 |
2.0959* |
1.9882 |
9.2202* |
|||||||||||
±SD |
0.0154 |
0.1220 |
0.1095 |
0.0434 |
0.0238 |
0.1035 |
0.1080 |
0.0863 |
0.3073 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G1R, F & 0 |
Mean |
0.0590 |
0.3688 |
0.4692 |
0.6375 |
0.1525 |
0.8816 |
1.7360 |
1.9808 |
7.2510 |
|||||||||||
±SD |
0.0107 |
0.1099 |
0.1049 |
0.1581 |
0.0252 |
0.0700 |
0.1980 |
0.0704 |
0.5332 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||
G4R, F & 1000 |
Mean |
0.0789* |
0.3649 |
0.4532 |
0.5133 |
0.1533 |
1.0073 |
1.7925 |
1.8895 |
8.0583 |
|||||||||||
±SD |
0.0111 |
0.0650 |
0.0937 |
0.1131 |
0.0257 |
0.3164 |
0.1536 |
0.1411 |
1.0192 |
||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 15. SUMMARY OF ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT(%)RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Epididymis |
Testes |
Heart |
Kidneys |
Brain |
Liver |
Prostate+Seminal vesicles with coagulating glands (PSC) |
||||||||||||||
G1, M & 0 |
Mean |
266.88 |
0.0241 |
0.1390 |
0.1527 |
0.3941 |
1.0233 |
0.3380 |
0.7919 |
0.7112 |
3.0142 |
0.6302 |
|||||||||||||
±SD |
26.22 |
0.0074 |
0.0429 |
0.0250 |
0.0386 |
0.1006 |
0.0410 |
0.0734 |
0.0864 |
0.4135 |
0.1227 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||||
G2, M & 100 |
Mean |
269.28 |
0.0244 |
0.1616 |
0.1987* |
0.4168 |
0.9969 |
0.3886 |
0.9621* |
0.7129 |
3.8483* |
0.7074 |
|||||||||||||
±SD |
21.68 |
0.0044 |
0.0182 |
0.0316 |
0.0191 |
0.1282 |
0.0275 |
0.0845 |
0.0683 |
0.4465 |
0.0700 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||||
G3, M & 300 |
Mean |
276.03 |
0.0236 |
0.1817 |
0.1884 |
0.4271 |
1.1139 |
0.4035* |
1.0700* |
0.7488 |
3.9980* |
0.8656* |
|||||||||||||
±SD |
16.65 |
0.0040 |
0.0129 |
0.0189 |
0.0263 |
0.0608 |
0.0463 |
0.0801 |
0.1222 |
0.2607 |
0.1828 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||||
G4, M & 1000 |
Mean |
228.95* |
0.0243 |
0.1446 |
0.1840 |
0.4477* |
1.2354* |
0.3901 |
0.9643* |
0.8038 |
4.2342* |
0.7731 |
|||||||||||||
±SD |
13.09 |
0.0010 |
0.0515 |
0.0152 |
0.0382 |
0.1185 |
0.0217 |
0.0830 |
0.0670 |
0.6522 |
0.1370 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||||
G1R, M & 0 |
Mean |
321.27 |
0.0148 |
0.1134 |
0.1514 |
0.3918 |
0.9080 |
0.3620 |
0.7477 |
0.6088 |
3.0095 |
0.8953 |
|||||||||||||
±SD |
38.28 |
0.0026 |
0.0425 |
0.0195 |
0.0558 |
0.1161 |
0.0356 |
0.0842 |
0.0699 |
0.1788 |
0.1008 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
||||||||||||||
G4R, M & 1000 |
Mean |
307.69 |
0.0184 |
0.1286 |
0.1780 |
0.3980 |
0.9921 |
0.4033 |
0.8841 |
0.6536 |
3.2694 |
0.8859 |
|||||||||||||
±SD |
18.09 |
0.0026 |
0.0080 |
0.0248 |
0.0235 |
0.0629 |
0.0352 |
0.1107 |
0.0566 |
0.2560 |
0.0950 |
||||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group;M: Male;R: Recovery; SD: Standard Deviation; n: Number of animals;*: Statistically significant (p<0.05)
TABLE 15 (Contd..,). SUMMARY OF ORGAN WEIGHT RELATIVE TO FASTING BODY WEIGHT (%) RECORD
Group, Sex & Dose (mg/kg body weight/day) |
Fasting Body Weight (g) |
Adrenals |
Thymus |
Spleen |
Uterus |
Ovaries |
Heart |
Kidneys |
Brain |
Liver |
|||||||||||||
G1, F & 0 |
Mean |
206.98 |
0.0333 |
0.2371 |
0.2183 |
0.2399 |
0.0758 |
0.4005 |
0.8635 |
0.9150 |
3.5821 |
||||||||||||
±SD |
18.48 |
0.0036 |
0.0367 |
0.0252 |
0.0495 |
0.0136 |
0.0292 |
0.0861 |
0.0841 |
0.3018 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G2, F & 100 |
Mean |
206.48 |
0.0389 |
0.2281 |
0.2204 |
0.2651 |
0.0705 |
0.4051 |
0.8646 |
0.8694 |
3.8530 |
||||||||||||
±SD |
8.63 |
0.0034 |
0.0420 |
0.0044 |
0.0596 |
0.0143 |
0.0141 |
0.0401 |
0.0537 |
0.1769 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G3, F & 300 |
Mean |
209.10 |
0.0331 |
0.2110 |
0.2313 |
0.2536 |
0.0745 |
0.3971 |
0.9407 |
0.9344 |
4.1201* |
||||||||||||
±SD |
7.03 |
0.0054 |
0.0525 |
0.0388 |
0.0558 |
0.0104 |
0.0151 |
0.0547 |
0.0325 |
0.3113 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4, F & 1000 |
Mean |
202.34 |
0.0399 |
0.2678 |
0.2648 |
0.2543 |
0.0719 |
0.4029 |
1.0393* |
0.9854 |
4.5709* |
||||||||||||
±SD |
14.44 |
0.0083 |
0.0746 |
0.0485 |
0.0229 |
0.0118 |
0.0396 |
0.0788 |
0.0611 |
0.2768 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G1R, F & 0 |
Mean |
231.70 |
0.0256 |
0.1578 |
0.2014 |
0.2743 |
0.0657 |
0.3805 |
0.7485 |
0.8564 |
3.1304 |
||||||||||||
±SD |
10.00 |
0.0053 |
0.0406 |
0.0376 |
0.0619 |
0.0090 |
0.0255 |
0.0677 |
0.0539 |
0.2156 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|||||||||||||
G4R, F & 1000 |
Mean |
231.78 |
0.0340* |
0.1591 |
0.1959 |
0.2205 |
0.0662 |
0.4384 |
0.7776 |
0.8158 |
3.4799 |
||||||||||||
±SD |
15.01 |
0.0040 |
0.0358 |
0.0419 |
0.0407 |
0.0108 |
0.1540 |
0.0997 |
0.0446 |
0.3997 |
|||||||||||||
n |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
G: Group; F: Female; R: Recovery; SD: Standard Deviation; n:number of animals;*: Statistically significant (p<0.05)
TABLE 16.SUMMARY OF GROSS PATHOLOGY FINDINGS
Organs/ Lesions |
Group |
G1 |
G1R |
G2 |
G3 |
G4 |
G4R |
||||||
Dose (mg/kg body weight/day) |
0 |
0 |
100 |
300 |
1000 |
1000 |
|||||||
Sex |
M |
F |
M |
F |
M |
F |
M |
F |
M |
F |
M |
F |
|
No. of Animals |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
No Abnormality Detected |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
The numeral indicates number of animal/s; M: Male; F: Female; G: Group.
TABLE 17.SUMMARY OFHISTOPATHOLOGY FINDINGS
Sex |
Male |
Female |
||
Group |
G1 |
G4 |
G1 |
G4 |
Dosage (mg/kg body weight/day) |
0 |
1000 |
0 |
1000 |
Liver |
5 |
5 |
5 |
5 |
MNC infiltration:Minimal |
0 |
0 |
1 |
1 |
Kidneys |
5 |
5 |
5 |
5 |
Cortex; tubular basophilia; unilateral : Minimal |
1 |
0 |
0 |
1 |
Lungs |
5 |
5 |
5 |
5 |
Perivascular MNC infiltration: Minimal |
1 |
1 |
0 |
0 |
Thyroid |
5 |
5 |
5 |
5 |
Ectopic thymus |
1 |
0 |
0 |
1 |
Note: The numeral indicates number of animal/s with lesion; G: group; MNC: Mononuclear cell.
Applicant's summary and conclusion
- Conclusions:
- Based on the observed results, the No Observed Adverse Effect Level (NOAEL) of test item Hostacor ITD is 1000 mg/kg/day when administered for a period of 28 consecutive days by oral (gavage) route to Sprague Dawley under the test conditions and doses employed.
- Executive summary:
The objective of this studywas to assess the toxic potential of the test item Hostacor ITD when administered for a period of 28 consecutive days repeatedly by oral (gavage) to Sprague Dawley rats. This studyprovidesinformation on major toxic effects, target organs, possibility of cumulative effects and also to assess the reversibility of effects (after 14 days recovery period) and an estimate of the No Observed Adverse Effect Level (NOAEL). This study wasperformed in accordance with OECD Guideline No. 407, “Repeated Dose 28-Day Oral Toxicity Study in Rodents” adopted on 03 October 2008.
A total of 60 Sprague Dawleyrats(30males +30females)were distributed to4mainand2recovery groups. Each main groupand recovery groupconsisted of 5animals/sex/group.The test item was formulated using corn oil.The animals allocated togroupsG2, G3 and G4/G4Rwere administeredwithoral dosesof100, 300 and 1000 mg/kg body weight/day of test item, respectivelythrough oral gavage.The animals allocated togroupG1/G1Rreceived vehicle corn oil. The vehicle/test item formulations were administered at an equivolume of 10 mL/kg.
The dose formulations wereanalyzed duringweek 1 andweek 4of the treatment period and the results indicated that the obtained concentrationswere within the acceptable range of 85 to 115%of the nominal concentrationwith less than 10% RelativeStandardDeviation.
All animals were observed once daily for clinical signs and twice daily for mortality; weekly for detailed clinical examination, body weight and feed consumption; ophthalmoscopic examination was performed during acclimatization and during week4for main groups (G1andG4) and during week6for recovery groups (G1RandG4R). Functional observational battery was performed during week4forallmain groupanimalsand during week6for recovery groupanimals(G1RandG4R).
At the end of treatment and recovery period (day 29 for main group and day 43 for recovery group), blood and urine samples were collected and analyzed. Subsequently, the animals were sacrificed and subjected to gross pathological examination and the organs were collected and subjected to histopathological examination.
Norelevantclinical signs of toxicity was observed in any of the vehicle or test item administered animals up tothe high dosegroup. Aslight wet perineum was observed ina fewhigh dose test item administered animals (males: 2/5 and females: 2/5 in main group animals; males: 1/5 and females: 2/5 in recovery group animals)which is not considered to be of toxicological relevance.
No treatment related changes in body weight, percent change in body weight with respect to day 1, feed consumption and ophthalmoscopic examination were noted. No adverse treatment related changes were noted in haematology, clinical chemistry and urinalysis parameters. No toxicologically significant changes were noted in organ weights and its ratios.
No treatment related gross and histopathology changes were noted in any organ and/or tissue.
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