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EC number: 239-555-0 | CAS number: 15520-05-5
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- DECEMBER 2020 to JULY 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- Adopted in 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2,2'-(octylimino)bisethanol
- EC Number:
- 239-555-0
- EC Name:
- 2,2'-(octylimino)bisethanol
- Cas Number:
- 15520-05-5
- Molecular formula:
- C12H27NO2
- IUPAC Name:
- 2-[(2-hydroxyethyl)(octyl)amino]ethan-1-ol
Constituent 1
- Specific details on test material used for the study:
- Batch No. ESD0033823
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Historically, the rat has been found to be a suitable model for pre-clinical safety evaluation studies and is recommended by regulatory agencies. The Wistar rat has shown to be sensitive to toxic effects of a variety of drugs and other chemicals. Therefore, the species and strain is a reasonable alternative to larger mammals for toxicity testing with respect to human safety assessment. This study is designed to use the fewest number of animals possible, consistent with the objectives of the study, contemporary scientific needs and standards, and in consideration of regulatory requirements.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Temperature : 19.5 to 24.7 °C
Relative humidity : 40 - 69%
Light/dark cycle (photoperiod) : 12 h light and 12 h dark cycle
Fresh air changes : Minimum 12 air-changes/hour
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- The dose formulations of vehicle/test item were administered to respective groups by oral route once daily for 90 days at the dose volume of 5 mL/kg b.w. Dose was administered using a calibrated disposable syringe attached to 16 gauge stainless steel ball tipped oral gavage needle. Dose volumes were calculated based on the most recently recorded body weight of individual animal.
- Vehicle:
- corn oil
- Details on oral exposure:
- The test item dose formulations and vehicle were administered orally by gavage.
Dose selection rationale: A 28-day repeated dose oral toxicity study of Genamin 3920 in Wistar rats conducted at 20, 100 and 500 mg/kg (ECHA, 2020). Mortality was observed at 500 mg/kg b.w. Maximum Tolerated Dose and No Observed Effect Level were 100 and 20 mg/kg b.w. respectively (REACH, EC number: 239-555-0 | CAS number: 15520-05-5). On the basis of published data, the highest dose (350 mg/kg b.w.) selected in this study is expected to produce toxicity. Further, lower doses of 25, 75 and 150 mg/kg b.w. were selected in order to produce a gradation of toxic effects, if any. Concurrent control group animals will be treated with vehicle alone.
In a prenatal developmental study (according to OECD 414) pregnant Wistar rats were administered the test item at the dose levels of 75, 150 and 350 through oral route, once daily, from gestation days (GD) 5 to 19. As mortality was observed at the dose level of 350 mg/kg/day (high dose) during different gestation days, the dose was reduced to 300 mg/kg/day for this group.
Based on all available data summerizd here the use of 350 mg/kg bw per day as highest dose in the OECD 408 study is scientifcally justified and in line with animal welfare consideration. - Analytical verification of doses or concentrations:
- yes
- Remarks:
- The results revealed homogenous distribution in the dose formulation. The observed concentrations at pre-dose, during 6th week and last week of treatment were in the range between 94.0% - 105.7% as compared to the nominal concentrations
- Details on analytical verification of doses or concentrations:
- The results revealed homogenous distribution in the dose formulation. The observed concentrations at pre-dose, during 6th week and last week of treatment were in the range between 94.0% - 105.7% as compared to the nominal concentrations
- Duration of treatment / exposure:
- 90 consecutive days
- Frequency of treatment:
- Once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 350 mg/kg bw/day (nominal)
- Remarks:
- Dose selection rationale: A 28-day repeated dose oral toxicity study of Genamin 3920 in Wistar rats conducted at 20, 100 and 500 mg/kg (ECHA, 2020). Mortality was observed at 500 mg/kg b.w. Maximum Tolerated Dose and No Observed Effect Level were 100 and 20 mg/kg b.w. respectively (REACH, EC number: 239-555-0 | CAS number: 15520-05-5- Study No 134233).
In a prenatal developmental study (according to OECD 414) pregnant Wistar rats were administered the test item at the dose levels of 75, 150 and 350 through oral route, once daily, from gestation days (GD) 5 to 19. As mortality was observed at the dose level of 350 mg/kg/day (high dose) during different gestation days, the dose was reduced to 300 mg/kg/day for this group.
On the basis of all published data, the highest dose (350 mg/kg b.w.) selected in this study is expected to produce toxicity. Further, lower doses of 25, 75 and 150 mg/kg b.w. were selected in order to produce a gradation of toxic effects, if any. Concurrent control group animals will be treated with vehicle alone.
Based on all available data summerizd here the use of 350 mg/kg bw per day as highest dose in the OECD 408 study is scientifcally justified and in line with animal welfare consideration.
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- Dose / conc.:
- 75 mg/kg bw/day (nominal)
- Dose / conc.:
- 25 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 m and 10 f in each main dose group; 5 m and 5 f in each recovery dose group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A 28-day repeated dose oral toxicity study of Genamin 3920 in Wistar rats conducted at 20, 100 and 500 mg/kg (ECHA, 2020). Mortality was observed at 500 mg/kg b.w. Maximum Tolerated Dose and No Observed Effect Level were 100 and 20 mg/kg b.w. respectively (REACH, EC number: 239-555-0 | CAS number: 15520-05-5). On the basis of published data, the highest dose (350 mg/kg b.w.) selected in this study is expected to produce toxicity. Further, lower doses of 25, 75 and 150 mg/kg b.w. were selected in order to produce a gradation of toxic effects, if any. Concurrent control group animals will be treated with vehicle alone. The doses were selected based on available literature and in consultation with the sponsor’s suggestions.
- Rationale for animal assignment (if not random): Animals were randomised into four treatment and one control groups with 10 rats/sex/group. Additionally, 5 /sex/group were maintained for control and high dose recovery. The animals were identified by accession numbers and randomised into treatment and control groups based on body weight. The body weight variation did not exceed ± 20% of the mean body weight range.
- Fasting period before blood sampling for clinical biochemistry:Blood was collected from overnight fasted (water allowed) animals via retro-orbital plexus under isoflurane anaesthesia:
- Rationale for selecting satellite groups: to check for reversibility or occurrence of delayed toxic effects.
- Post-exposure recovery period in satellite groups: 28 days post 90-day treatment
Examinations
- Observations and examinations performed and frequency:
- Clinical Observation
Routine cage-side observations were made for all animals once a day throughout the study period for general signs of toxicity and twice a day to check morbidity and mortality.
Detailed Clinical Examination
Detailed clinical examination was carried out once in a week (± 1 day) with exception during last week of treatment and recovery periods. During detailed clinical examination, all animals were observed for changes in skin, fur, eyes, mucous membrane, occurrence of secretions and excretions, autonomic activity such as lacrimation, piloerection, pupil size, unusual respiratory pattern, changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes and bizarre behaviour.
Ophthalmoscopic Examination
Ophthalmologic examination for all group animals was carried out once prior to randomisation for all animals and during the last week of treatment period, for control (G1) and test item high dose group (G5) animals. As no abnormality was observed at test item high dose (G5), the examination was not extended to lower and recovery groups. Mydriasis was induced before examination by instilling 1% Tropicamide.
Body Weight
Individual animal body weights for all the groups of animals were recorded prior to initiation of treatment and at weekly intervals thereafter.
Feed Consumption
Feed consumption was measured at weekly intervals.
Neurobehavioral Examination / FOB (functional observation battery)
Animals in the cage were observed for posture and convulsions.
The animals were observed for the ease of removal from the cage. During handling observation, the animals were observed for ease of handling, palpebral closure, lacrimation, eye examination, piloerection and salivation.
Animals were placed in an open field arena with a clean absorbent paper underneath. Animals were observed for approximately 2 minutes for gait, mobility, arousal, respiration, tonic and clonic movements, stereotypic behaviour, bizarre behaviour, urination, defecation, vocalizations and rearing.
Sensory reactivity and neuromuscular measurements were performed on all animals belonging to the main and recovery groups during the last week of exposure/recovery periods respectively.
Sensory reactivity of all animals were assessed by subjecting them to approach response, touch response, click response, tail pinch response and pupil response measurements.
The animal was held in a supine position and dropped from a height of approximately 30 cm. The ease and uprightness of landing was recorded in a single score as normal or abnormal.
The fore limb and hind limb grip strengths (g) of the animals were measured with the help of a grip strength meter (Orchid Scientific). The fore and hind limb grip strength of each animal was measured 3 consecutive times and average values were calculated.
The tarsal joint pad of each hind foot of the animals was marked with non-permanent non-toxic ink. The animals were suspended in a prone position and dropped from a height of approximately 30 cm on to a recording sheet. The procedure was repeated thrice and the average was calculated.
Motor activity (total and ambulatory activities) were evaluated for all main and recovery group animals during the last week of exposure and recovery periods respectively using OPTO VARIMEX and automated animal activity measuring system (Columbus Instruments, USA) equipped with a computer analyser. Animals were monitored for 3 consecutive ten-minute intervals allowing examination of exploratory and acclimatization activity levels. Stereotypic activity was calculated by subtracting ambulatory activity from total activity.
Clinical Pathology
Clinical Pathology investigations were performed for all animals of main groups and recovery groups on Day 91 and Day 119 respectively. Blood was collected from overnight fasted (water allowed) animals via retro-orbital plexus under isoflurane anaesthesia:
Blood (~0.5 mL) was collected in tubes containing 10% w/v K2EDTA and samples were analysed for following haematological parameters as listed below using haematology analyser (ADVIA, 2120, Siemens).
Red Blood Cell count (RBC)
White Blood Cell count (WBC)
Haemoglobin (HGB)
Haematocrit (HCT)
Mean Corpuscular Haemoglobin Concentration (MCHC)
Mean Corpuscular Volume (MCV)
Mean Corpuscular Haemoglobin (MCH)
Platelet Count (PLT)
Mean Platelet Volume (MPV)
Red Cell Distribution Width (RDW)
Reticulocyte Count (RET)
Differential Leukocyte Count (DLC)
Neutrophils (Neu)
Lymphocytes (Lymp)
Basophils (Baso)
Eosinophils (Eosi)
Monocytes (Mono)
Blood (~1 mL) for coagulation parameters were collected in tubes containing 3.2% w/v Sodium Citrate (Approximately 1:9 ratio of anticoagulant to blood). Following coagulation parameters as listed below were analysed using automatic coagulometer (Diagnostica Start-4, Stago, France).
Prothrombin Time (PT)
Activated Partial Thromboplastin Time (APTT)
Blood (~2 mL) was collected in tubes without anticoagulant. Serum was collected by centrifugation at 3500 rpm for 10 min at 4 ºC. Samples were analysed with an automatic biochemical analyser (Vitros 4600, Ortho Clinical Diagnostics) using standard reagent kits and laboratory methodology. The following parameters were analysed.
Glucose (GLU)
Total Protein (TP)
Albumin (Alb)
Globulin (Glo)
Albumin/Globulin ratio (A/GR) (Calculated)
Alanine Aminotransferase (ALT)
Aspartate Aminotransferase (AST)
Alkaline Phosphatase (ALP)
Total Bilirubin (BIL)
Blood Urea Nitrogen (BUN)
Creatinine (Crea)
Sodium (Na)
Potassium (K)
Chloride (Cl)
Calcium (Ca)
Phosphorus (P)
Triglycerides (TRG)
Total Cholesterol (CHO)
HDL Cholesterol (HDL)
LDL Cholesterol (LDL)
Total bile acids
Urea
T3
T4
TSH
Urine output (24 hour ± 30 min) was measured for all surviving animals during last week of treatment and recovery periods.
Urine was collected from all surviving animals using metabolic cages on experimental Days 91 and 119 for main and recovery group animals respectively. Urine was analysed for following parameters using urine analyser (Uriscan Pro II).
Timed Urine Volume Collection#
Colour
Appearance/Clarity*
Specific Gravity
pH
Protein
Glucose
Ketone Bodies
Urobilinogen
Bilirubin
Leucocytes
Nitrites
Blood/Blood cells
An aliquot of the urine sample was centrifuged and the resulting deposit spread on a microscope slide. The deposit was examined for the presence of Epithelial cells (E), Crystals (Cr) and other abnormal constituents (A). - Sacrifice and pathology:
- All animals of main and recovery groups were euthanized on Day 91 and Day 119 respectively by CO2 asphyxiation followed by exsanguination. Before scheduled euthanasia, the animals were fasted overnight (water allowed) and terminal body weights were recorded. The animals were subjected to detailed gross pathological observation during necropsy.
All the organs as listed and specified below were collected, weighed and preserved.
All gross lesions
Adrenal glands*
Aorta
Brain - Cerebrum, Cerebellum, Mid brain, & Medulla
Epididymides*
Eyes with optic nerve
Femur with bone marrow
Heart
Kidneys*
Large intestine (Caecum, Colon and Rectum)
Liver*
Lungs with bronchi and bronchioles
Lymph node (Mesenteric and Mandibular)
Oesophagus
Ovaries*
Pancreas
Pituitary#
Prostate with Seminal vesicles and coagulating glands
Salivary glands- Submandibular, Parotid, Sublingual
Sciatic Nerve
Skeletal muscle
Skin along with Mammary Glands
Small intestine (Duodenum, Jejunum, Ileum with Peyer’s Patch)
Spinal Cord (Cervical, Thoracic, Lumbar)
Spleen
Stomach
Testes*
Thymus
Thyroid and parathyroid gland#
Trachea
Urinary bladder
Uterus with cervix
Vagina
Lungs were preserved by inflation with fixative.
*- Paired organs were weighed together. #-Weighed after partial fixation
Relative organ weights were calculated for those organs weighed using the following formula.
Relative organ weight (%) = absolute organ weight (g)/terminal body weight (g) X 100
The organs except testes and eyes were preserved in 10% neutral buffered formalin. Testes were preserved in Modified Davidson’s fixative and eyes were preserved in Davidson’s fixative.
Bone marrow smears were prepared for all animals of main and recovery groups at the time of necropsy by paint brush technique and stained with Giemsa stain. As there was no treatment related changes observed in haematological parameters, examination of bone marrow smears was not performed.
At the time of necropsy, progressive sperm motility was determined manually in vas deferens sperm samples for all the males. Additionally, sperm smears were also prepared from vas deferens of all males and fixed in methanol. Sperm morphology evaluation was restricted to control and high-dose males. As there was no treatment related changes observed in high dose group, the evaluation was not extended to lower dose and recovery high dose groups. The oestrus cycle of all females were determined by taking vaginal smears before terminal sacrifice.
Histopathology examination was carried out on all dead animals, gross lesions and preserved organs of vehicle control and high dose main group animals. As there was a histophatological changes observed in stomach, trachea and kidneys in high dose group/found dead animals, the evaluation was extended to lower dose and recovery high dose groups.
Tissues selected for histopathological evaluation were processed, embedded and sections were cut at 3 - 5 μ. Sections were placed on grease-free slides and stained with Haematoxylin and Eosin. A 5-step grading system of minimum, mild, moderate, marked and severe was used to rank microscopic findings for comparison among groups. Data was compiled based on incidences and severity of changes. - Statistics:
- The data was analysed using Graphpad Prism, version 4.00. Statistical comparisons were carried out for all continuous data between treatment and control groups using parametric (one-way analysis of variance (ANOVA), Dunnett's t-Test) or non-parametric (Kruskal-Wallis test, Mann Whitney’s Test) test procedures. The choice of parametric or non-parametric test was based on whether the groups satisfy the homogeneity of variance as evaluated by Bartlett’s test. Statistical significance was evaluated at p ≤ 0.05 and/or p ≤ 0.01. All quantitative data was summarized and expressed as Mean ± SD. Comparison between recovery groups was done by Student’s t-test.
Note: Statistical analysis of Bilirubin and LDL parameters was not performed as the results of the parameters for most of the animals were below detectable range.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Animals from mid high (150 mg/kg bw per day) (Male: 3/10; Female: 9/10) and high (350 mg/kg bw per day) (Male: 9/10; Female: 8/10) dose groups displayed transient salivation from Days 51 to 60.
Weekly detailed clinical observations did not reveal any abnormalities in animals treated with test item as well as vehicle control. One male animal from high dose (350 mg/kg bw per day)exhibited bronchial rales and one female animal from vehicle control was having mild alopecia-bilateral from Week 9 to Week 13. Due to the isolated incidences these effects are not considered to be of toxicological relevance.
For more details see attached table - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One animal each from low (T107/023) and mid high (T107/067) dose groups were found dead on Day 41 presumed to be gavaging error.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There were no significant changes in weekly body weights of the all test item treated animals when compared to the vehicle control.
Statistically significant increase in body weight was recorded on Day 43 and Day 50 in recovery high dose females. However, no correlating changes were observed in feed consumption and normal body weight gain was observed at the end of treatment period and was considered as incidental finding
For more details see attached table - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No treatment related changes were recorded in the average daily feed consumption of the test item treated groups when compared to vehicle control throughout the treatment and recovery periods. An isolated marginal (~12%) decrease in feed consumption of high dose recovery females was observed on Day 29 when compared to recovery vehicle control animals.
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No ocular abnormalities were detected in ophthalmoscopic examinations carried out during pre-dose observations in all animals and during the last week of treatment period.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No treatment related changes were observed in any of the haematology parameters in test item treated groups including recovery groups as compared with respective vehicle controls. Significant increase in MCH in low dose females, HCT in recovery high dose males and decrease in relative eosinophil count in mid and mid high dose group females were considered not related to test item as the values are within historical control ranges and because of absence of dose relationship or associated changes in other parameters.
For more details see attached table - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Significant increase in triglycerides and calcium was observed in high dose females. In absence of associated changes in other parameters, it was not attributed to test item effect. Significant decrease in BUN and urea in low and high dose females were not dose dependent. Significant increase in cholesterol, BUN, HDL, T3 and urea was observed in recovery high dose males and significant increase in globulin, cholesterol, HDL, chloride and bile acids was observed in recovery high dose females when compared to concurrent control groups. These changes were within the normal biological range, hence were considered as incidental findings and not related to test item treatment.
For more details see attached table - Endocrine findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No treatment related significant changes were observed in any of the urinalysis parameters in main and recovery group animals in both sexes when compared to respective vehicle controls. Significant increase in pH in high dose males, decrease in pH in low, mid and mid high dose group females and increase in volume in recovery high dose males were observed. In absence of associated histopathological changes/dose dependency, these changes were considered not related to test item treatment. Furthermore, all the changes observed are within historical control ranges.
For more details see attached table - Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No relevant effects were observed in any of the parameters of the functional observation battery performed at the end of the treatment and recovery periods.
Statistically significant decrease in foot splay and increase in stereotypic behaviour was observed in recovery high dose females and males respectively. The animals from the recovery high dose were apparently healthy and in absence of test item related changes in other neurobehavioral observations, these changes were considered incidental.
Sensory Reactivity Measurements
All animals of test item treated groups as well as the control groups displayed normal approach, tail pinch, touch, click and pupil responses.
Air Righting Reflex
Air righting reflex of all the animals of both the control and test item treated groups were found to be normal.
Grip Strength
No alterations in the fore and hind limb grip strength were recorded in any of the treated group animals as compared to concurrent control groups
Hind Limb Foot Splay
The hind limb foot splay of all test item treated groups were comparable to concurrent control groups. Statistically significant decrease in foot splay was observed in recovery high dose females. The observed difference was minimal and in absence of test item related changes in other neurobehavioral observations, the observed change did not have any toxicological significance.
Motor Activity
Administration of test item did not cause any significant alterations in the total, ambulatory and stereotypic activities of treated rats as compared to respective control group animalsStatistically significant increase in stereotypic behaviour was observed in recovery high dose males when compared to recovery vehicle control. The animals from the recovery high dose were apparently healthy, in absence of test item related changes in other neurobehavioral observations the observed change did not have any toxicological significance
For more details see attached table - Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No test item related changes were observed in both absolute and relative organ weight in main and recovery group animals in both sexes when compared to respective vehicle controls. However, a significant decrease was observed in relative weight of brain in high dose females and heart and thyroid in recovery high dose females when compared to respective vehicle controls. Absence of related histopathology finding in high dose animals, the decreased relative weights were considered not related to test item treatment. Furthermore, all the changes observed are within historical control ranges
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Distended and empty gastro intestinal tract were recorded in one found dead animal each from low (T107/023) and mid high (T107/067) dose groups. However, correlated histopathology finding in GI tract was not observed. Bronchial rales and dyspnea which were observed before the death of these animals could be an indication for misgavaging. Small unilateral seminal vesicle observed in one control male and enlarged bilateral testes observed in one 150 mg/kg test item treated male. Correlated histopathology findings observed in seminal vesicles (atrophy) and testes (dilatation) revealed that the observed findings were considered as spontaneous/incidental.
For more details see attached table - Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- One male (T107/081) sacrificed terminally from 350 mg/kg dose group showed multifocal necrosis in kidneys together with squamous cell hyperplasia in non-glandular stomach. In addition, two males from the same group showed mononuclear cell infiltration in non-glandular stomach. However, in absence correlating changes in other parameters, it was considered as test item related non-adverse finding and due to the irritating properties of the test item.As the kidney findings were limited to one animal each from low dose and high dose groups it was considered as incidental not related to test item. However, histopathology findings observed in stomach were considered as test item related.
No histopathological changes were observed in stomach and kidneys of recovery high dose group animals.
Other histopathology findings observed in liver (inflammatory cell infiltrate), kidneys (casts, basophilc tubule and inflammatory cell infiltrate), spleen (EMH), thymus (Ectopic tissue), testes (tubular dilatation and tubular degeneration), epididymides (cell debris), prostate (atrophy and inflammatory cell infiltrate), seminal vesicles (atrophy), trachea (inflammatory cell infiltrate) and heart (inflammatory cell infiltrate) across groups and the sex were considered as spontaneous/incidental.
For more details see attached table - Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- No test item related mortalities were observed during study period. One animal each from low (T107/023) and mid high (T107/067) dose groups were found dead on Day 41. Bronchial rales and dyspnea were observed before the death of these animals. On microscopic evaluation, erosion in trachea was observed in mid high dose group animal which was considered as an indicative of regurgitation/wrong dosing. Further, multifocal necrosis in kidneys along with mild to marked atrophic changes were noted in spleen and thymus of low dose group animal. Despite the aforesaid changes in low dose, there were no other microscopic observations that explained the cause of death. These deaths are presumed to be incidental and due to gavaging error as brochniail rales and dyspenea occurred after application of the test item and before the death. Forthemore these deaths occured in a low or mid high dose animals and there were no adverse findings in any other rats at any dose level.
Animals from mid high (Male: 3/10; Female: 9/10) and high (Male: 9/10; Female: 8/10) dose groups displayed transient salivation from Days 51 to 60. Transient salivation is clinical finding frequently observed after oral gavaging of local irritant effect of test item and is not assumed to be a sign of systemic toxicity (REACH, EC number: 239-555-0 | CAS number: 15520-05-5).
In addition, few isolated incidences of bronchial rales (Male - 25, 150 and 350 mg/kg b.w.: 1/10), dyspnea (Male - 25 and 150 mg/kg b.w.: 1/10), alopecia (Female - 0 mg/kg b.w.: 1/10) and hyperactivity (Female - 75 mg/kg b.w.: 2/10) were observed in different experimental groups.
Detailed Clinical Observations
Weekly detailed clinical observations did not reveal any abnormalities in animals treated with test item as well as vehicle control. One male animal from high dose exhibited bronchial rales and one female animal from vehicle control was having mild alopecia-bilateral from Week 9 to Week 13. Due to the isolated incidences these effects are not considered to be of toxicological relevance.
The data was analysed using Graphpad Prism, version 4.00. Statistical comparisons were carried out for all continuous data between treatment and control groups using parametric (one-way analysis of variance (ANOVA), Dunnett's t-Test) or non-parametric (Kruskal-Wallis test, Mann Whitney’s Test) test procedures. The choice of parametric or non-parametric test was based on whether the groups satisfy the homogeneity of variance as evaluated by Bartlett’s test. Statistical significance was evaluated at p ≤ 0.05 and/or p ≤ 0.01. All quantitative data was summarized and expressed as Mean ± SD. Comparison between recovery groups was done by Student’s t-test.
Note: Statistical analysis of Bilirubin and LDL parameters was not performed as the results of the parameters for most of the animals were below detectable range.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 350 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
Summary of Detailed Clinical Examination
Gender: Male No. of Animals/Group/Sex: 10
Group & Dose (mg/kg b.w.) | Clinical Signs | No. of Animals Showing Clinical Signs | ||||||
Week | ||||||||
# | 1 | 2 | 3 | 4 | 5 | 6 | ||
G1 & 0 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G2 & 25 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 9 |
G3 & 75 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G4 & 150 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 9 |
G5 & 350 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 9 |
Bronchial Rales | - | - | - | - | - | - | 1 |
Group & Dose (mg/kg b.w.) | Clinical Signs | No. of Animals Showing Clinical Signs | |||||
Week | |||||||
7 | 8 | 9 | 10 | 11 | 12 | ||
G1 & 0 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
G2 & 25 | No Abnormality Detected | 9 | 9 | 9 | 9 | 9 | 9 |
G3 & 75 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
G4 & 150 | No Abnormality Detected | 9 | 9 | 9 | 9 | 9 | 9 |
G5 & 350 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
Gender: Female No. of Animals/Group/Sex: 10
Group & Dose (mg/kg b.w.) | Clinical Signs | No. of Animals Showing Clinical Signs | ||||||
Week | ||||||||
# | 1 | 2 | 3 | 4 | 5 | 6 | ||
G1 & 0 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G2 & 25 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G3 & 75 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G4 & 150 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
G5 & 350 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Group & Dose (mg/kg b.w.) | Clinical Signs | No. of Animals Showing Clinical Signs | |||||
Week | |||||||
7 | 8 | 9 | 10 | 11 | 12 | ||
G1 & 0 | No Abnormality Detected | 10 | 10 | 9 | 9 | 9 | 9 |
Alopecia (1, bilateral) | - | - | 1 | 1 | 1 | 1 | |
G2 & 25 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
G3 & 75 | No Abnormality Detected | 10 | 10 | 10 | 8 | 10 | 10 |
Hyperactive | - | - | - | 2 | - | - | |
G4 & 150 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
G5 & 350 | No Abnormality Detected | 10 | 10 | 10 | 10 | 10 | 10 |
Summary of Neurobehavioral Examination
Gender: Male No. of Animals/Group/Sex: 10
Parameters | Group & Dose (mg/kg b.w.) | ||||
G1 (0) | G2 (25) | G3 (75) | G4 (150) | G5 (350) | |
Home Cage Observations | |||||
Posture | |||||
Sitting or standing alert, watching | 8 | 6 | 6 | 2 | 5 |
Curled up often asleep | 0 | 1 | 0 | 0 | 1 |
Rearing | 2 | 2 | 4 | 7 | 4 |
Convulsions | |||||
Absent | 10 | 9 | 10 | 9 | 10 |
Handling Observations | |||||
Ease of Removal | |||||
Very easy | 8 | 8 | 9 | 9 | 10 |
Easy | 2 | 1 | 1 | 0 | 0 |
Handling Reactivity | |||||
Easy | 10 | 9 | 10 | 9 | 10 |
Palpebral Closure | |||||
Wide open | 10 | 9 | 10 | 9 | 10 |
Lacrimation | |||||
No external lacrimation | 10 | 9 | 10 | 9 | 10 |
Eye examination | |||||
Normal | 10 | 9 | 10 | 9 | 10 |
Piloerection | |||||
Absent | 10 | 9 | 10 | 9 | 10 |
Salivation | |||||
No external Salivation | 10 | 9 | 10 | 9 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G1 (0) | G2 (25) | G3 (75) | G4 (150) | G5 (350) | ||
Open Field Observations | ||||||
Gait | ||||||
Normal | 10 | 9 | 10 | 9 | 10 | |
Mobility | ||||||
Normal | 10 | 9 | 10 | 9 | 10 | |
Arousal | ||||||
Low | 10 | 9 | 10 | 8 | 10 | |
High | 0 | 0 | 0 | 1 | 0 | |
Respiration | ||||||
Normal | 10 | 9 | 10 | 9 | 10 | |
Tonic Movement | ||||||
Absent | 10 | 9 | 10 | 9 | 10 | |
Clonic Movement | ||||||
Absent | 10 | 9 | 10 | 9 | 10 | |
Stereotype | ||||||
Absent | 10 | 9 | 10 | 9 | 10 | |
Bizzare Behaviour | ||||||
Absent | 10 | 9 | 10 | 9 | 10 | |
No. of Rears (Mean ± S.D.) | 9.3 ± 3.2 | 9.67±3.28 | 8± 3.71 | 12.44±3.64 | 10.1±2.8 | |
No. of Vocalisations | 0 | 10 | 9 | 10 | 9 | 10 |
No. of Urine Pools | 0 | 10 | 5 | 9 | 8 | 9 |
1 to 3 | 0 | 4 | 1 | 1 | 1 | |
No. of Faecal Bolus | 0 | 9 | 7 | 9 | 8 | 9 |
1 to 3 | 0 | 1 | 0 | 1 | 1 | |
4 to 6 | 1 | 1 | 1 | 0 | 0 |
Parameters | Group & Dose (mg/kg b.w.) | |
G6 (0) | G7 (350) | |
Home Cage Observations | ||
Posture | ||
Sitting or standing alert, watching | 3 | 4 |
Curled up often asleep | 0 | 1 |
Rearing | 2 | 0 |
Convulsions | ||
Absent | 5 | 5 |
Handling Observations | ||
Ease of Removal | ||
Very easy | 5 | 5 |
Handling Reactivity | ||
Easy | 4 | 4 |
Moderately difficult | 1 | 1 |
Palpebral Closure | ||
Wide open | 5 | 5 |
Lacrimation | ||
No external lacrimation | 5 | 5 |
Eye examination | ||
Normal | 5 | 5 |
Piloerection | ||
Absent | 5 | 5 |
Salivation | ||
No external Salivation | 5 | 5 |
Parameters | Group & Dose (mg/kg b.w.) | ||
G6 (0) | G7 (350) | ||
Open Field Observations | |||
Gait | |||
Normal | 5 | 5 | |
Mobility | |||
Normal | 5 | 5 | |
Arousal | |||
Low | 4 | 5 | |
High | 1 | 0 | |
Respiration | |||
Normal | 5 | 5 | |
Tonic Movement | |||
Absent | 5 | 5 | |
Clonic Movement | |||
Absent | 5 | 5 | |
Stereotype | |||
Absent | 5 | 5 | |
Bizzare Behaviour | |||
Absent | 5 | 5 | |
N° of Rears (Mean ± S.D.) | 10 ± 2.35 | 9.4 ± 2.7 | |
N° of Vocalisations | 0 | 5 | 5 |
N° of Urine Pools | 0 | 3 | 4 |
1 to 3 | 2 | 1 | |
N° of Faecal Bolus | 0 | 4 | 4 |
1 to 3 | 1 | 1 |
Gender: Female No. of Animals/Group/Sex: 10
Parameters | Group & Dose (mg/kg b.w.) | ||||
G1 (0) | G2 (25) | G3 (75) | G4 (150) | G5 (350) | |
Home Cage Observations | |||||
Posture | |||||
Sitting or standing alert, watching | 2 | 4 | 3 | 6 | 2 |
Curled up often asleep | 1 | 0 | 1 | 1 | 7 |
Rearing | 7 | 6 | 6 | 3 | 1 |
Convulsions | |||||
Absent | 10 | 10 | 10 | 10 | 10 |
Handling Observations | |||||
Ease of Removal | |||||
Very easy | 10 | 10 | 10 | 10 | 10 |
Handling Reactivity | |||||
Easy | 10 | 10 | 10 | 10 | 10 |
Palpebral Closure | |||||
Wide open | 10 | 10 | 10 | 10 | 10 |
Lacrimation | |||||
No external lacrimation | 10 | 10 | 10 | 10 | 10 |
Eye examination | |||||
Normal | 10 | 10 | 10 | 10 | 10 |
Piloerection | |||||
Absent | 10 | 10 | 10 | 10 | 10 |
Salivation | |||||
No external Salivation | 10 | 10 | 10 | 10 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G1 (0) | G2 (25) | G3 (75) | G4 (150) | G5 (350) | ||
Open Field Observations | ||||||
Gait |
| |||||
Normal | 10 | 10 | 10 | 10 | 10 | |
Mobility |
| |||||
Normal | 10 | 10 | 10 | 10 | 10 | |
Arousal |
| |||||
Low | 9 | 8 | 8 | 10 | 9 | |
High | 1 | 1 | 2 | 0 | 1 | |
Very high | 0 | 1 | 0 | 0 | 0 | |
Respiration | ||||||
Normal | 10 | 10 | 10 | 10 | 10 | |
Tonic Movement | ||||||
Absent | 10 | 10 | 10 | 10 | 10 | |
Clonic Movement | ||||||
Absent | 10 | 10 | 10 | 10 | 10 | |
Stereotype | ||||||
Absent | 10 | 10 | 10 | 10 | 10 | |
Bizzare Behaviour | ||||||
Absent | 10 | 10 | 10 | 10 | 10 | |
No. of Rears (Mean ± S.D.) | 15.9±4.82 | 15.7±5.72 | 16.2±4.52 | 14.8±3.97 | 13.1±3.84 | |
No. of Vocalisations | 0 | 10 | 10 | 10 | 10 | 10 |
No. of Urine Pools | 0 | 10 | 9 | 9 | 7 | 0 |
1 to 3 | 0 | 1 | 1 | 3 | 0 | |
No. of Faecal Bolus | 0 | 10 | 8 | 10 | 9 | 10 |
1 to 3 | 0 | 2 | 0 | 1 | 0 | |
4 to 6 | 0 | 0 | 0 | 0 | 0 |
Gender: Female No. of Animals/Group/Sex: 5
Parameters | Group & Dose (mg/kg b.w.) | |
G6 (0) | G7 (350) | |
Home Cage Observations | ||
Posture | ||
Sitting or standing alert, watching | 3 | 2 |
Rearing | 2 | 3 |
Convulsions | ||
Absent | 5 | 5 |
Handling Observations | ||
Ease of Removal | ||
Very easy | 5 | 5 |
Handling Reactivity | ||
Easy | 5 | 5 |
Palpebral Closure | ||
Wide open | 5 | 5 |
Lacrimation | ||
No external lacrimation | 5 | 5 |
Eye examination | ||
Normal | 5 | 5 |
Piloerection | ||
Absent | 5 | 5 |
Salivation | ||
No external Salivation | 5 | 5 |
Parameters | Group & Dose (mg/kg b.w.) | ||
G6 (0) | G7 (350) | ||
Open Field Observations | |||
Gait | |||
Normal | 5 | 5 | |
Mobility | |||
Normal | 5 | 5 | |
Arousal | |||
Low | 4 | 4 | |
High | 1 | 1 | |
Respiration | |||
Normal | 5 | 5 | |
Tonic Movement | |||
Absent | 5 | 5 | |
Clonic Movement | |||
Absent | 5 | 5 | |
Stereotype | |||
Absent | 5 | 5 | |
Bizzare Behaviour | |||
Absent | 5 | 5 | |
N° of Rears (Mean ± S.D.) | 11.4 ± 1.14 | 11.2 ± 2.28 | |
N° of Vocalisations | 0 | 5 | 5 |
N° of Urine Pools | 0 | 5 | 5 |
N° of Faecal Bolus | 0 | 5 | 5 |
Summary of Motor Activity, Grip Strength and Hind Limb Foot Splay Record
Gender: Male
Parameter | Group & Dose (mg/kg b. w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | |||||||||
Total Count | 5299.90 | 1484.45 | 10 | 5292.89 | 1549.11 | 9 | 5219.10 | 1981.30 | 10 |
Ambulatory Count | 4025.80 | 1275.65 | 10 | 4102.78 | 1361.38 | 9 | 3995.70 | 1722.22 | 10 |
Stereotypic Count | 1274.10 | 242.20 | 10 | 1190.11 | 235.26 | 9 | 1223.40 | 274.84 | 10 |
Grip Strength (g) | |||||||||
Fore limb | 1040.75 | 54.89 | 10 | 1037.06 | 106.74 | 9 | 991.16 | 29.63 | 10 |
Hind limb | 722.96 | 56.94 | 10 | 714.46 | 51.90 | 9 | 756.58 | 55.75 | 10 |
Hind Limb Foot Splay (mm) | |||||||||
Foot Splay | 81.23 | 26.49 | 10 | 85.85 | 23.12 | 9 | 89.83 | 18.35 | 10 |
Parameter | Group & Dose (mg/kg b. w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | ||||||
Total Count | 6127.22 | 1236.41 | 9 | 6197.50 | 1095.19 | 10 |
Ambulatory Count | 4725.56 | 1019.83 | 9 | 4806.50 | 978.48 | 10 |
Stereotypic Count | 1401.67 | 259.08 | 9 | 1391.00 | 159.55 | 10 |
Grip Strength (g) | ||||||
Fore limb | 1047.68 | 43.45 | 9 | 1080.83 | 94.71 | 10 |
Hind limb | 762.12 | 32.64 | 9 | 755.29 | 43.63 | 10 |
Hind Limb Foot Splay (mm) | ||||||
Foot Splay | 79.85 | 20.05 | 9 | 71.20 | 16.97 | 10 |
Parameter | Group & Dose (mg/kg b. w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | ||||||
Total Count | 4013.20 | 1428.58 | 5 | 5820.80 | 1452.61 | 5 |
Ambulatory Count | 2991.00 | 1263.13 | 5 | 4500.60 | 1374.62 | 5 |
Stereotypic Count | 1022.20 | 181.41 | 5 | 1320.20↑ | 139.23 | 5 |
Grip Strength (g) | ||||||
Fore limb | 1000.19 | 58.94 | 5 | 1008.91 | 24.57 | 5 |
Hind limb | 782.49 | 43.70 | 5 | 796.49 | 48.99 | 5 |
Hind Limb Foot Splay (mm) | ||||||
Foot Splay | 83.93 | 13.07 | 5 | 88.73 | 22.36 | 5 |
Gender: Female
Parameter | Group & Dose (mg/kg b. w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | |||||||||
Total Count | 8118.20 | 2843.48 | 10 | 7783.40 | 1882.50 | 10 | 6820.70 | 1624.90 | 10 |
Ambulatory Count | 6464.30 | 2585.44 | 10 | 6179.40 | 1665.90 | 10 | 5288.90 | 1397.31 | 10 |
Stereotypic Count | 1653.90 | 295.89 | 10 | 1604.00 | 284.55 | 10 | 1531.80 | 244.00 | 10 |
Grip Strength (g) | |||||||||
Fore limb | 937.49 | 72.88 | 10 | 946.14 | 63.27 | 10 | 918.25 | 56.61 | 10 |
Hind limb | 630.03 | 35.42 | 10 | 641.39 | 52.37 | 10 | 618.03 | 29.23 | 10 |
Hind Limb Foot Splay (mm) | |||||||||
Foot Splay | 59.90 | 10.52 | 10 | 57.27 | 15.71 | 10 | 56.07 | 10.77 | 10 |
Parameter | Group & Dose (mg/kg b. w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | ||||||
Total Count | 7798.70 | 1763.36 | 10 | 6845.20 | 1855.11 | 10 |
Ambulatory Count | 6178.90 | 1597.72 | 10 | 5301.20 | 1680.68 | 10 |
Stereotypic Count | 1619.80 | 265.97 | 10 | 1544.00 | 206.96 | 10 |
Grip Strength (g) | ||||||
Fore limb | 931.21 | 68.27 | 10 | 976.50 | 77.00 | 10 |
Hind limb | 680.39 | 44.45 | 10 | 666.03 | 59.90 | 10 |
Hind Limb Foot Splay (mm) | ||||||
Foot Splay | 61.70 | 14.49 | 10 | 70.20 | 18.82 | 10 |
Parameter | Group & Dose (mg/kg b. w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Motor Activity (number of counts) | ||||||
Total Count | 6356.80 | 1757.20 | 5 | 6242.60 | 1088.20 | 5 |
Ambulatory Count | 5053.20 | 1419.08 | 5 | 4971.40 | 808.83 | 5 |
Stereotypic Count | 1303.60 | 347.21 | 5 | 1271.20 | 289.55 | 5 |
Grip Strength (g) | ||||||
Fore limb | 785.32 | 31.37 | 5 | 749.11 | 26.82 | 5 |
Hind limb | 655.05 | 13.07 | 5 | 651.53 | 16.99 | 5 |
Hind Limb Foot Splay (mm) | ||||||
Foot Splay | 77.67 | 4.28 | 5 | 65.27↓ | 6.72 | 5 |
Summary of Ophthalmologic Examination
Gender: Male No. of Animals/Group/Sex: 10
Group & Dose (mg/kg b.w.) | Observation | No. of Animals | |||
Pre-dose | Day 90 | ||||
Right Eye | Left Eye | Right Eye | Left Eye | ||
G1 & 0 | NAD | 10 | 10 | 10 | 10 |
G2 & 25 | NAD | 10 | 10 | - | - |
G3 & 75 | NAD | 10 | 10 | - | - |
G4 & 150 | NAD | 10 | 10 | - | - |
G5 & 350 | NAD | 10 | 10 | 10 | 10 |
Gender: Male No. of Animals/Group/Sex: 5
Group & Dose (mg/kg b.w.) | Observation | No. of Animals | |
Pre-dose | |||
Right Eye | Left Eye | ||
G6 & 0 | NAD | 5 | 5 |
G7 & 350 | NAD | 5 | 5 |
Gender: Female No. of Animals/Group/Sex: 10
Group & Dose (mg/kg b.w.) | Observation | No. of Animals | |||
Pre-dose | Day 90 | ||||
Right Eye | Left Eye | Right Eye | Left Eye | ||
G1 & 0 | NAD | 10 | 10 | 10 | 10 |
G2 & 25 | NAD | 10 | 10 | - | - |
G3 & 75 | NAD | 10 | 10 | - | - |
G4 & 150 | NAD | 10 | 10 | - | - |
G5 & 350 | NAD | 10 | 10 | 10 | 10 |
Gender: Female No. of Animals/Group/Sex: 5
Group & Dose (mg/kg b.w.) | Observation | No. of Animals | |
Pre-dose | |||
Right Eye | Left Eye | ||
G6 & 0 | NAD | 5 | 5 |
G7 & 350 | NAD | 5 | 5 |
Summary of Body Weight (g)
Gender: Male
Week | Group & Dose (mg/kg b.w.) |
| ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | ||||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | ||
# | 229.72 | 16.44 | 10 | 225.23 | 15.34 | 10 | 227.51 | 18.08 | 10 | |
1 | 294.92 | 16.56 | 10 | 291.27 | 16.78 | 10 | 295.09 | 20.10 | 10 | |
2 | 344.04 | 24.91 | 10 | 342.71 | 15.72 | 10 | 348.01 | 25.01 | 10 | |
3 | 378.54 | 28.87 | 10 | 382.38 | 17.30 | 10 | 386.88 | 29.36 | 10 | |
4 | 414.05 | 34.07 | 10 | 420.20 | 18.12 | 10 | 426.68 | 33.97 | 10 | |
5 | 439.53 | 36.89 | 10 | 449.89 | 17.99 | 10 | 455.62 | 37.46 | 10 | |
6 | 466.59 | 41.96 | 10 | 479.97 | 19.43 | 9 | 486.43 | 44.48 | 10 | |
7 | 490.86 | 46.10 | 10 | 505.08 | 20.18 | 9 | 510.48 | 45.66 | 10 | |
8 | 513.79 | 50.72 | 10 | 524.50 | 20.54 | 9 | 531.03 | 52.25 | 10 | |
9 | 528.00 | 53.85 | 10 | 540.23 | 19.44 | 9 | 549.84 | 52.90 | 10 | |
10 | 543.64 | 54.30 | 10 | 559.33 | 21.80 | 9 | 569.97 | 57.59 | 10 | |
11 | 557.18 | 58.33 | 10 | 574.04 | 27.06 | 9 | 584.60 | 61.26 | 10 | |
12 | 564.12 | 57.39 | 10 | 582.16 | 30.53 | 9 | 591.63 | 65.50 | 10 | |
13 | 562.49 | 59.04 | 10 | 580.37 | 30.58 | 9 | 591.20 | 58.72 | 10 |
Week | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
# | 229.26 | 19.45 | 10 | 227.10 | 13.54 | 10 |
1 | 290.86 | 22.98 | 10 | 282.87 | 17.29 | 10 |
2 | 340.26 | 26.81 | 10 | 331.55 | 24.82 | 10 |
3 | 377.59 | 31.75 | 10 | 372.70 | 27.82 | 10 |
4 | 412.19 | 33.71 | 10 | 408.75 | 25.47 | 10 |
5 | 438.66 | 37.30 | 10 | 432.88 | 31.67 | 10 |
6 | 457.71 | 40.50 | 9 | 454.31 | 37.23 | 10 |
7 | 481.00 | 40.88 | 9 | 479.47 | 38.51 | 10 |
8 | 501.26 | 38.99 | 9 | 496.20 | 38.44 | 10 |
9 | 519.37 | 38.23 | 9 | 509.71 | 40.85 | 10 |
10 | 536.40 | 39.78 | 9 | 527.20 | 39.06 | 10 |
11 | 547.19 | 40.74 | 9 | 534.26 | 41.72 | 10 |
12 | 553.20 | 42.08 | 9 | 541.53 | 43.73 | 10 |
13 | 554.40 | 42.39 | 9 | 542.59 | 44.77 | 10 |
Week | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
# | 218.58 | 21.88 | 5 | 228.77 | 16.73 | 5 |
1 | 285.05 | 16.72 | 5 | 286.63 | 25.47 | 5 |
2 | 328.47 | 19.29 | 5 | 325.36 | 10.60 | 5 |
3 | 362.05 | 25.69 | 5 | 355.97 | 12.24 | 5 |
4 | 395.06 | 29.04 | 5 | 398.61 | 18.67 | 5 |
5 | 419.38 | 29.82 | 5 | 433.96 | 22.02 | 5 |
6 | 447.37 | 28.05 | 5 | 457.80 | 28.18 | 5 |
7 | 468.48 | 34.04 | 5 | 481.53 | 31.78 | 5 |
8 | 488.26 | 37.57 | 5 | 504.12 | 39.05 | 5 |
9 | 500.80 | 36.17 | 5 | 521.07 | 46.06 | 5 |
10 | 517.28 | 34.11 | 5 | 537.99 | 51.84 | 5 |
11 | 534.47 | 35.78 | 5 | 554.43 | 63.25 | 5 |
12 | 535.76 | 35.73 | 5 | 566.11 | 55.76 | 5 |
13 | 534.81 | 35.05 | 5 | 570.83 | 52.13 | 5 |
14 | 539.14 | 33.59 | 5 | 583.30 | 52.95 | 5 |
15 | 550.37 | 38.03 | 5 | 595.36 | 47.03 | 5 |
16 | 560.09 | 37.47 | 5 | 607.78 | 51.94 | 5 |
17 | 566.34 | 38.99 | 5 | 612.79 | 48.53 | 5 |
Gender: Female
Week | Group & Dose (mg/kg b.w.) |
| ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | ||||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | ||
# | 175.18 | 12.76 | 10 | 177.64 | 10.15 | 10 | 177.04 | 11.95 | 10 | |
1 | 198.75 | 12.62 | 10 | 201.45 | 15.43 | 10 | 199.43 | 11.91 | 10 | |
2 | 217.40 | 16.54 | 10 | 218.77 | 14.74 | 10 | 218.45 | 20.44 | 10 | |
3 | 234.33 | 20.82 | 10 | 234.86 | 15.91 | 10 | 232.76 | 21.69 | 10 | |
4 | 250.53 | 23.47 | 10 | 254.86 | 21.01 | 10 | 250.55 | 21.08 | 10 | |
5 | 260.99 | 21.18 | 10 | 263.11 | 20.28 | 10 | 263.04 | 21.67 | 10 | |
6 | 273.17 | 20.35 | 10 | 273.63 | 21.28 | 10 | 275.16 | 21.86 | 10 | |
7 | 283.67 | 21.46 | 10 | 281.84 | 18.81 | 10 | 280.22 | 22.00 | 10 | |
8 | 288.77 | 23.58 | 10 | 289.63 | 21.21 | 10 | 289.39 | 24.33 | 10 | |
9 | 297.13 | 22.83 | 10 | 295.48 | 22.64 | 10 | 298.61 | 26.47 | 10 | |
10 | 289.11 | 21.59 | 10 | 291.85 | 23.10 | 10 | 291.52 | 25.86 | 10 | |
11 | 296.71 | 23.97 | 10 | 299.90 | 23.19 | 10 | 302.36 | 22.27 | 10 | |
12 | 301.81 | 27.81 | 10 | 304.91 | 23.44 | 10 | 308.68 | 29.20 | 10 | |
13 | 304.28 | 24.29 | 10 | 306.78 | 23.74 | 10 | 308.83 | 25.41 | 10 |
Week | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
# | 177.52 | 13.41 | 10 | 174.11 | 9.54 | 10 |
1 | 202.28 | 17.27 | 10 | 201.10 | 13.28 | 10 |
2 | 224.23 | 22.47 | 10 | 224.57 | 11.16 | 10 |
3 | 237.10 | 21.41 | 10 | 243.60 | 14.74 | 10 |
4 | 252.36 | 20.38 | 10 | 258.59 | 19.39 | 10 |
5 | 264.68 | 20.41 | 10 | 270.98 | 21.62 | 10 |
6 | 277.40 | 19.45 | 10 | 290.59 | 21.15 | 10 |
7 | 280.01 | 24.51 | 10 | 298.53 | 22.39 | 10 |
8 | 289.18 | 24.48 | 10 | 308.41 | 22.27 | 10 |
9 | 295.98 | 25.73 | 10 | 311.72 | 28.57 | 10 |
10 | 293.72 | 25.30 | 10 | 314.90 | 23.55 | 10 |
11 | 303.45 | 27.77 | 10 | 327.46 | 29.31 | 10 |
12 | 310.49 | 27.54 | 10 | 335.74 | 27.88 | 10 |
13 | 310.66 | 27.23 | 10 | 332.97 | 30.76 | 10 |
Week | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
# | 166.76 | 8.73 | 5 | 170.32 | 9.49 | 5 |
1 | 194.85 | 11.35 | 5 | 192.54 | 11.11 | 5 |
2 | 206.87 | 9.34 | 5 | 218.35 | 7.76 | 5 |
3 | 223.74 | 11.47 | 5 | 234.27 | 13.95 | 5 |
4 | 239.58 | 12.45 | 5 | 245.79 | 16.19 | 5 |
5 | 246.22 | 12.13 | 5 | 258.85 | 17.20 | 5 |
6 | 250.85 | 10.31 | 5 | 274.56*+ | 16.17 | 5 |
7 | 259.28 | 14.34 | 5 | 284.44*+ | 17.02 | 5 |
8 | 270.32 | 13.09 | 5 | 286.48 | 22.54 | 5 |
9 | 275.96 | 11.39 | 5 | 292.72 | 18.70 | 5 |
10 | 271.23 | 12.52 | 5 | 296.72 | 24.75 | 5 |
11 | 281.96 | 12.43 | 5 | 299.61 | 22.68 | 5 |
12 | 288.01 | 16.17 | 5 | 309.40 | 23.10 | 5 |
13 | 291.32 | 10.73 | 5 | 307.54 | 24.41 | 5 |
14 | 292.02 | 14.56 | 5 | 313.79 | 22.39 | 5 |
15 | 296.77 | 11.83 | 5 | 313.50 | 17.56 | 5 |
16 | 299.05 | 11.87 | 5 | 316.83 | 20.21 | 5 |
17 | 298.05 | 13.13 | 5 | 316.68 | 22.36 | 5 |
Summary of Haematology Parameters
Gender: Male
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 8.75 | 0.32 | 10 | 8.69 | 0.44 | 9 | 8.46 | 0.30 | 10 |
HGB (g/dL) | 14.61 | 0.44 | 10 | 14.59 | 0.61 | 9 | 14.29 | 0.75 | 10 |
HCT (%) | 44.91 | 1.26 | 10 | 44.67 | 1.54 | 9 | 43.61 | 1.89 | 10 |
MCV (fL) | 51.34 | 1.15 | 10 | 51.46 | 1.60 | 9 | 51.58 | 1.83 | 10 |
MCH (pg) | 16.70 | 0.43 | 10 | 16.78 | 0.60 | 9 | 16.91 | 0.82 | 10 |
MCHC (g/dL) | 32.54 | 0.36 | 10 | 32.62 | 0.59 | 9 | 32.75 | 0.61 | 10 |
RDW (%) | 13.17 | 0.48 | 10 | 12.91 | 0.20 | 9 | 12.92 | 0.51 | 10 |
RET(x109 cells/L) | 54.61 | 20.75 | 10 | 50.09 | 10.99 | 9 | 57.59 | 9.46 | 10 |
PLT (103cells/µL) | 1140.30 | 144.08 | 10 | 1087.78 | 108.08 | 9 | 1058.20 | 151.22 | 10 |
MPV (fL) | 6.72 | 0.28 | 10 | 6.72 | 0.13 | 9 | 6.80 | 0.41 | 10 |
WBC (103cells/µL) | 9.77 | 2.68 | 10 | 8.21 | 1.83 | 9 | 8.80 | 1.62 | 10 |
NEU (103cells/µL) | 2.34 | 1.18 | 10 | 1.80 | 0.74 | 9 | 2.03 | 0.49 | 10 |
LYM (103cells/µL) | 6.70 | 2.68 | 10 | 5.86 | 1.09 | 9 | 6.17 | 1.36 | 10 |
MON (103cells/µL) | 0.43 | 0.34 | 10 | 0.24 | 0.05 | 9 | 0.31 | 0.13 | 10 |
EOS (103cells/µL) | 0.15 | 0.08 | 10 | 0.15 | 0.04 | 9 | 0.16 | 0.06 | 10 |
BAS (103cells/µL) | 0.02 | 0.01 | 10 | 0.02 | 0.01 | 9 | 0.02 | 0.01 | 10 |
NEU (%) | 24.64 | 14.57 | 10 | 21.47 | 4.34 | 9 | 23.38 | 5.80 | 10 |
LYM (%) | 67.63 | 17.91 | 10 | 71.87 | 4.90 | 9 | 69.98 | 6.42 | 10 |
MON (%) | 4.68 | 4.39 | 10 | 3.03 | 0.65 | 9 | 3.40 | 0.99 | 10 |
EOS (%) | 1.43 | 0.61 | 10 | 1.88 | 0.32 | 9 | 1.77 | 0.46 | 10 |
BAS (%) | 0.25 | 0.07 | 10 | 0.22 | 0.10 | 9 | 0.18 | 0.08 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 8.97 | 0.43 | 9 | 8.69 | 0.36 | 10 |
HGB (g/dL) | 14.80 | 0.58 | 9 | 14.37 | 0.44 | 10 |
HCT (%) | 45.21 | 1.33 | 9 | 44.48 | 1.60 | 10 |
MCV (fL) | 50.43 | 1.32 | 9 | 51.21 | 1.13 | 10 |
MCH (pg) | 16.52 | 0.58 | 9 | 16.56 | 0.53 | 10 |
MCHC (g/dL) | 32.73 | 0.64 | 9 | 32.33 | 0.78 | 10 |
RDW (%) | 12.77 | 0.74 | 9 | 12.77 | 0.18 | 10 |
RET(x109 cells/L) | 49.28 | 18.86 | 9 | 55.78 | 6.77 | 10 |
PLT (103cells/µL) | 1148.00 | 143.92 | 9 | 1095.00 | 109.41 | 10 |
MPV (fL) | 6.89 | 0.29 | 9 | 6.82 | 0.38 | 10 |
WBC (103cells/µL) | 7.93 | 1.79 | 9 | 8.30 | 0.90 | 10 |
NEU (103cells/µL) | 1.94 | 0.75 | 9 | 2.15 | 0.80 | 10 |
LYM (103cells/µL) | 5.49 | 1.16 | 9 | 5.67 | 1.05 | 10 |
MON (103cells/µL) | 0.26 | 0.09 | 9 | 0.22 | 0.08 | 10 |
EOS (103cells/µL) | 0.13 | 0.03 | 9 | 0.13 | 0.03 | 10 |
BAS (103cells/µL) | 0.01 | 0.01 | 9 | 0.02 | 0.01 | 10 |
NEU (%) | 24.13 | 4.78 | 9 | 26.12 | 9.72 | 10 |
LYM (%) | 69.43 | 4.44 | 9 | 68.29 | 9.91 | 10 |
MON (%) | 3.21 | 0.91 | 9 | 2.71 | 0.90 | 10 |
EOS (%) | 1.78 | 0.60 | 9 | 1.60 | 0.30 | 10 |
BAS (%) | 0.18 | 0.08 | 9 | 0.18 | 0.08 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 8.57 | 0.30 | 5 | 8.84 | 0.16 | 5 |
HGB (g/dL) | 14.22 | 0.40 | 5 | 14.76 | 0.35 | 5 |
HCT (%) | 43.40 | 1.16 | 5 | 45.20↑ | 1.02 | 5 |
MCV (fL) | 50.64 | 1.52 | 5 | 51.10 | 1.23 | 5 |
MCH (pg) | 16.62 | 0.61 | 5 | 16.68 | 0.41 | 5 |
MCHC (g/dL) | 32.78 | 0.33 | 5 | 32.66 | 0.29 | 5 |
RDW (%) | 13.46 | 0.21 | 5 | 13.56 | 0.34 | 5 |
RET(x109 cells/L) | 146.68 | 22.82 | 5 | 160.88 | 22.67 | 5 |
PLT (103cells/µL) | 977.20 | 106.61 | 5 | 1032.00 | 93.78 | 5 |
MPV (fL) | 7.84 | 0.28 | 5 | 7.76 | 0.11 | 5 |
WBC (103cells/µL) | 9.03 | 1.40 | 5 | 8.02 | 1.95 | 5 |
NEU (103cells/µL) | 1.83 | 0.36 | 5 | 1.50 | 0.23 | 5 |
LYM (103cells/µL) | 6.63 | 1.29 | 5 | 5.97 | 1.64 | 5 |
MON (103cells/µL) | 0.26 | 0.06 | 5 | 0.25 | 0.08 | 5 |
EOS (103cells/µL) | 0.18 | 0.05 | 5 | 0.16 | 0.05 | 5 |
BAS (103cells/µL) | 0.02 | 0.00 | 5 | 0.02 | 0.01 | 5 |
NEU (%) | 20.36 | 3.32 | 5 | 19.20 | 2.85 | 5 |
LYM (%) | 73.14 | 4.03 | 5 | 74.18 | 3.20 | 5 |
MON (%) | 3.04 | 1.24 | 5 | 3.04 | 0.53 | 5 |
EOS (%) | 1.98 | 0.51 | 5 | 2.00 | 0.32 | 5 |
BAS (%) | 0.22 | 0.04 | 5 | 0.18 | 0.04 | 5 |
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 7.80 | 0.37 | 10 | 7.57 | 0.24 | 10 | 7.78 | 0.33 | 10 |
HGB (g/dL) | 14.01 | 0.69 | 10 | 13.84 | 0.35 | 10 | 13.53 | 0.62 | 10 |
HCT (%) | 42.04 | 2.22 | 10 | 41.39 | 1.26 | 10 | 40.94 | 1.64 | 10 |
MCV (fL) | 53.92 | 0.89 | 10 | 54.67 | 1.27 | 10 | 52.64 | 0.95 | 10 |
MCH (pg) | 17.97 | 0.55 | 10 | 18.28*+ | 0.43 | 10 | 17.39 | 0.43 | 10 |
MCHC (g/dL) | 33.35 | 0.82 | 10 | 33.46 | 0.81 | 10 | 33.02 | 0.37 | 10 |
RDW (%) | 12.14 | 0.47 | 10 | 11.70 | 0.42 | 10 | 12.10 | 0.66 | 10 |
RET(x109 cells/L) | 58.60 | 15.09 | 10 | 51.10 | 14.58 | 10 | 61.42 | 18.96 | 10 |
PLT (103cells/µL) | 991.70 | 249.59 | 10 | 975.20 | 148.69 | 10 | 987.70 | 113.01 | 10 |
MPV (fL) | 7.08 | 0.29 | 10 | 7.09 | 0.32 | 10 | 7.13 | 0.38 | 10 |
WBC (103cells/µL) | 6.13 | 2.44 | 10 | 4.25 | 1.23 | 10 | 5.00 | 1.53 | 10 |
NEU (103cells/µL) | 1.27 | 0.67 | 10 | 0.78 | 0.25 | 10 | 0.96 | 0.47 | 10 |
LYM (103cells/µL) | 4.39 | 1.63 | 10 | 3.17 | 0.96 | 10 | 3.66 | 0.99 | 10 |
MON (103cells/µL) | 0.17 | 0.08 | 10 | 0.11 | 0.05 | 10 | 0.23 | 0.24 | 10 |
EOS (103cells/µL) | 0.20 | 0.17 | 10 | 0.11 | 0.06 | 10 | 0.09 | 0.04 | 10 |
BAS (103cells/µL) | 0.01 | 0.01 | 10 | 0.01 | 0.01 | 10 | 0.01 | 0.01 | 10 |
NEU (%) | 20.13 | 4.73 | 10 | 18.62 | 4.08 | 10 | 18.62 | 3.37 | 10 |
LYM (%) | 72.58 | 5.38 | 10 | 74.65 | 4.88 | 10 | 74.04 | 4.41 | 10 |
MON (%) | 2.74 | 0.58 | 10 | 2.53 | 0.61 | 10 | 4.33 | 4.14 | 10 |
EOS (%) | 3.10 | 1.50 | 10 | 2.59 | 1.10 | 10 | 1.82*- | 0.90 | 10 |
BAS (%) | 0.18 | 0.09 | 10 | 0.14 | 0.10 | 10 | 0.13 | 0.05 | 10 |
Key: N = No. of Animals, *+ = significantly high at p ≤0.05 as compared to G1, *- = significantly low at p ≤0.05 as compared to G1
Gender: Female
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 7.71 | 0.28 | 10 | 7.63 | 0.50 | 10 |
HGB (g/dL) | 13.68 | 0.41 | 10 | 13.55 | 0.92 | 10 |
HCT (%) | 41.36 | 1.03 | 10 | 40.96 | 2.41 | 10 |
MCV (fL) | 53.64 | 1.06 | 10 | 53.70 | 1.33 | 10 |
MCH (pg) | 17.75 | 0.34 | 10 | 17.76 | 0.57 | 10 |
MCHC (g/dL) | 33.05 | 0.35 | 10 | 33.09 | 0.45 | 10 |
RDW (%) | 11.93 | 0.45 | 10 | 12.10 | 0.35 | 10 |
RET(x109 cells/L) | 51.30 | 12.26 | 10 | 51.32 | 10.97 | 10 |
PLT (103cells/µL) | 971.10 | 118.01 | 10 | 917.90 | 69.74 | 10 |
MPV (fL) | 7.10 | 0.26 | 10 | 7.15 | 0.21 | 10 |
WBC (103cells/µL) | 4.82 | 0.94 | 10 | 4.60 | 1.02 | 10 |
NEU (103cells/µL) | 0.93 | 0.27 | 10 | 1.15 | 0.56 | 10 |
LYM (103cells/µL) | 3.55 | 0.81 | 10 | 3.12 | 1.21 | 10 |
MON (103cells/µL) | 0.18 | 0.11 | 10 | 0.16 | 0.13 | 10 |
EOS (103cells/µL) | 0.09 | 0.04 | 10 | 0.10 | 0.06 | 10 |
BAS (103cells/µL) | 0.01 | 0.01 | 10 | 0.01 | 0.01 | 10 |
NEU (%) | 19.45 | 4.62 | 10 | 26.27 | 16.14 | 10 |
LYM (%) | 73.50 | 4.88 | 10 | 66.20 | 19.03 | 10 |
MON (%) | 4.02 | 3.41 | 10 | 3.93 | 4.29 | 10 |
EOS (%) | 1.76*- | 0.85 | 10 | 2.09 | 1.05 | 10 |
BAS (%) | 0.13 | 0.05 | 10 | 0.15 | 0.08 | 10 |
Key: N = No. of Animals, *- = significantly low at p ≤0.05 as compared to G1
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
RBC (106cells/µL) | 7.65 | 0.22 | 5 | 7.75 | 0.30 | 5 |
HGB (g/dL) | 14.10 | 0.40 | 5 | 14.30 | 0.59 | 5 |
HCT (%) | 42.24 | 1.41 | 5 | 41.84 | 1.31 | 5 |
MCV (fL) | 55.22 | 1.63 | 5 | 54.02 | 1.60 | 5 |
MCH (pg) | 18.44 | 0.54 | 5 | 18.44 | 0.51 | 5 |
MCHC (g/dL) | 33.40 | 0.43 | 5 | 34.18 | 0.68 | 5 |
RDW (%) | 11.90 | 0.51 | 5 | 11.98 | 0.90 | 5 |
RET(x109 cells/L) | 110.92 | 10.45 | 5 | 107.18 | 23.95 | 5 |
PLT (103cells/µL) | 911.40 | 65.54 | 5 | 921.00 | 116.55 | 5 |
MPV (fL) | 7.76 | 0.32 | 5 | 7.92 | 0.35 | 5 |
WBC (103cells/µL) | 3.55 | 0.72 | 5 | 4.23 | 1.48 | 5 |
NEU (103cells/µL) | 0.68 | 0.19 | 5 | 0.75 | 0.29 | 5 |
LYM (103cells/µL) | 2.62 | 0.50 | 5 | 3.21 | 1.10 | 5 |
MON (103cells/µL) | 0.09 | 0.05 | 5 | 0.11 | 0.07 | 5 |
EOS (103cells/µL) | 0.10 | 0.02 | 5 | 0.10 | 0.04 | 5 |
BAS (103cells/µL) | 0.01 | 0.00 | 5 | 0.01 | 0.01 | 5 |
NEU (%) | 19.24 | 2.79 | 5 | 17.70 | 2.84 | 5 |
LYM (%) | 73.86 | 2.20 | 5 | 76.08 | 3.25 | 5 |
MON (%) | 2.48 | 1.24 | 5 | 2.48 | 0.64 | 5 |
EOS (%) | 2.80 | 0.60 | 5 | 2.48 | 0.69 | 5 |
BAS (%) | 0.20 | 0.12 | 5 | 0.10 | 0.00 | 5 |
Summary of Coagulation Parameters
Gender: Male
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
PT (Sec) | 20.05 | 1.61 | 10 | 20.77 | 1.75 | 9 | 18.51 | 2.22 | 10 |
APTT (Sec) | 18.48 | 2.60 | 10 | 20.87 | 2.65 | 9 | 18.85 | 2.87 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
PT (Sec) | 18.87 | 2.13 | 9 | 18.81 | 2.02 | 10 |
APTT (Sec) | 18.30 | 1.75 | 9 | 18.75 | 2.21 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
PT (Sec) | 20.98 | 2.79 | 5 | 19.96 | 1.30 | 5 |
APTT (Sec) | 15.24 | 2.43 | 5 | 16.28 | 1.37 | 5 |
Gender: Female
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
PT (Sec) | 16.04 | 1.16 | 10 | 15.87 | 1.19 | 10 | 16.91 | 1.67 | 10 |
APTT (Sec) | 19.20 | 4.39 | 10 | 18.13 | 3.64 | 10 | 18.67 | 4.63 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
PT (Sec) | 15.79 | 1.35 | 10 | 16.02 | 1.22 | 10 |
APTT (Sec) | 17.55 | 2.55 | 10 | 18.07 | 2.83 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
PT (Sec) | 20.54 | 0.47 | 5 | 18.16↓ | 1.95 | 5 |
APTT (Sec) | 16.60 | 1.35 | 5 | 17.08 | 0.81 | 5 |
Key: N = Number of animals, ↓ = significantly low at p ≤0.05 as compared to G6
Summary of Clinical Chemistry Parameters
Gender: Male
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 117.70 | 6.85 | 10 | 116.00 | 7.87 | 9 | 123.50 | 26.07 | 10 |
TP (g/dL) | 6.39 | 0.12 | 10 | 6.38 | 0.19 | 9 | 6.25 | 0.22 | 10 |
ALB (g/dL) | 3.86 | 0.13 | 10 | 3.87 | 0.16 | 9 | 3.73 | 0.22 | 10 |
GLO (g/dL) | 2.53 | 0.09 | 10 | 2.51 | 0.08 | 9 | 2.50 | 0.09 | 10 |
A/G Ratio | 1.53 | 0.07 | 10 | 1.53 | 0.07 | 9 | 1.49 | 0.11 | 10 |
TRG (mg/dL) | 89.30 | 30.25 | 10 | 103.67 | 36.60 | 9 | 112.10 | 34.01 | 10 |
CHO(mg/dL) | 70.80 | 11.84 | 10 | 68.11 | 11.39 | 9 | 57.52 | 11.75 | 10 |
ALT (U/L) | 35.50 | 6.93 | 10 | 32.33 | 7.97 | 9 | 43.10 | 33.85 | 10 |
AST (U/L) | 97.00 | 20.34 | 10 | 85.89 | 22.87 | 9 | 117.10 | 96.79 | 10 |
ALP (U/L) | 61.90 | 10.31 | 10 | 66.67 | 12.01 | 9 | 70.60 | 14.18 | 10 |
BUN (mg/dL) | 14.10 | 2.69 | 10 | 14.78 | 2.64 | 9 | 13.90 | 2.42 | 10 |
CRE (mg/dL) | 0.60 | 0.09 | 10 | 0.62 | 0.07 | 9 | 0.62 | 0.06 | 10 |
Na (mmol/L) | 149.00 | 1.33 | 10 | 149.44 | 1.24 | 9 | 148.90 | 1.52 | 10 |
K (mmol/L) | 4.48 | 0.23 | 10 | 4.44 | 0.33 | 9 | 4.47 | 0.43 | 10 |
Cl (mmol/L) | 117.70 | 1.83 | 10 | 118.00 | 2.06 | 9 | 117.20 | 2.70 | 10 |
Ca (mg/dL) | 11.56 | 0.19 | 10 | 11.54 | 0.26 | 9 | 11.66 | 0.32 | 10 |
P (mg/dL) | 7.14 | 0.49 | 10 | 6.94 | 0.45 | 9 | 6.99 | 0.68 | 10 |
HDL (mg/dL) | 39.47 | 8.26 | 10 | 41.42 | 7.75 | 9 | 33.86 | 7.70 | 10 |
Total bile acids (µmol/L) | 16.55 | 10.24 | 10 | 16.44 | 10.95 | 9 | 18.36 | 16.12 | 10 |
Urea (mg/dL) | 30.39 | 5.60 | 10 | 31.62 | 5.64 | 9 | 29.75 | 5.19 | 10 |
T3 (ng/dL) | 61.43 | 10.23 | 10 | 68.16 | 15.67 | 9 | 62.33 | 9.40 | 10 |
T4 (µg/dL) | 4.30 | 1.07 | 10 | 4.09 | 1.16 | 9 | 4.02 | 0.82 | 10 |
TSH (µIU/mL) | 2.74 | 1.64 | 10 | 1.88 | 0.98 | 9 | 1.19 | 0.63 | 10 |
Key: N = No. of Animals
Note: The results of Bilirubin and LDL for majority of animals were below detectable range and hence mean and SD could not be calculated
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 122.11 | 14.26 | 9 | 122.70 | 20.30 | 10 |
TP (g/dL) | 6.41 | 0.22 | 9 | 6.34 | 0.24 | 10 |
ALB (g/dL) | 3.86 | 0.16 | 9 | 3.86 | 0.20 | 10 |
GLO (g/dL) | 2.56 | 0.11 | 9 | 2.50 | 0.08 | 10 |
A/G Ratio | 1.51 | 0.12 | 9 | 1.54 | 0.08 | 10 |
TRG (mg/dL) | 109.33 | 35.31 | 9 | 102.40 | 23.63 | 10 |
CHO(mg/dL) | 69.83 | 11.87 | 9 | 69.54 | 9.55 | 10 |
ALT (U/L) | 49.67 | 45.04 | 9 | 34.60 | 11.69 | 10 |
AST (U/L) | 115.22 | 92.74 | 9 | 87.50 | 25.78 | 10 |
ALP (U/L) | 67.78 | 16.68 | 9 | 70.80 | 17.69 | 10 |
BUN (mg/dL) | 14.22 | 2.28 | 9 | 14.40 | 2.99 | 10 |
CRE (mg/dL) | 0.61 | 0.06 | 9 | 0.61 | 0.03 | 10 |
Na (mmol/L) | 149.78 | 1.64 | 9 | 149.10 | 2.28 | 10 |
K (mmol/L) | 4.66 | 0.23 | 9 | 4.68 | 0.35 | 10 |
Cl (mmol/L) | 118.22 | 2.22 | 9 | 118.40 | 2.72 | 10 |
Ca (mg/dL) | 11.73 | 0.34 | 9 | 11.47 | 0.47 | 10 |
P (mg/dL) | 7.02 | 0.37 | 9 | 6.87 | 0.55 | 10 |
HDL (mg/dL) | 39.79 | 7.16 | 9 | 40.60 | 4.99 | 10 |
Total bile acids (µmol/L) | 7.77 | 4.70 | 9 | 7.17 | 2.87 | 10 |
Urea (mg/dL) | 30.44 | 4.88 | 9 | 30.82 | 6.40 | 10 |
T3 (ng/dL) | 56.95 | 7.54 | 9 | 54.22 | 10.54 | 10 |
T4 (µg/dL) | 3.63 | 0.64 | 9 | 3.40 | 0.94 | 10 |
TSH (µIU/mL) | 1.48 | 0.43 | 9 | 1.84 | 1.04 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 147.40 | 8.96 | 5 | 134.60 | 18.85 | 5 |
TP (g/dL) | 6.22 | 0.26 | 5 | 6.36 | 0.23 | 5 |
ALB (g/dL) | 3.68 | 0.29 | 5 | 3.76 | 0.19 | 5 |
GLO (g/dL) | 2.54 | 0.09 | 5 | 2.56 | 0.13 | 5 |
A/G Ratio | 1.46 | 0.11 | 5 | 1.48 | 0.08 | 5 |
TRG (mg/dL) | 110.20 | 29.13 | 5 | 98.00 | 22.02 | 5 |
CHO(mg/dL) | 59.26 | 2.43 | 5 | 76.74 ↑ | 15.24 | 5 |
ALT (U/L) | 40.00 | 7.11 | 5 | 41.80 | 10.89 | 5 |
AST (U/L) | 113.80 | 36.42 | 5 | 110.60 | 26.35 | 5 |
ALP (U/L) | 70.00 | 11.64 | 5 | 82.20 | 9.83 | 5 |
BUN (mg/dL) | 14.60 | 1.67 | 5 | 17.20 ↑ | 1.10 | 5 |
CRE (mg/dL) | 0.58 | 0.04 | 5 | 0.60 | 0.07 | 5 |
Na (mmol/L) | 140.80 | 1.48 | 5 | 140.40 | 0.55 | 5 |
K (mmol/L) | 4.74 | 0.30 | 5 | 4.64 | 0.19 | 5 |
Cl (mmol/L) | 114.40 | 1.82 | 5 | 114.40 | 1.14 | 5 |
Ca (mg/dL) | 10.96 | 0.42 | 5 | 11.16 | 0.21 | 5 |
P (mg/dL) | 6.48 | 0.20 | 5 | 6.96 | 0.54 | 5 |
HDL (mg/dL) | 30.51 | 2.67 | 5 | 42.37 ↑ | 8.37 | 5 |
Total bile acids (µmol/L) | 20.38 | 19.37 | 5 | 12.90 | 8.19 | 5 |
Urea (mg/dL) | 31.24 | 3.58 | 5 | 36.81↑ | 2.34 | 5 |
T3 (ng/dL) | 31.97 | 2.14 | 5 | 39.71↑↑ | 3.12 | 5 |
T4 (µg/dL) | 3.14 | 0.43 | 5 | 3.64 | 0.34 | 5 |
TSH (µIU/mL) | 2.87 | 1.30 | 5 | 3.58 | 1.65 | 5 |
Key: N = No. of Animals, = significantly high at p ≤0.05 as compared to G6, = significantly high at p ≤0.01 as compared to G6
Note: The results of Bilirubin and LDL for majority of animals were below detectable range and hence mean and SD could not be calculated
Gender: Female
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 118.50 | 15.63 | 10 | 127.70 | 29.12 | 10 | 107.80 | 22.13 | 10 |
TP (g/dL) | 6.28 | 0.30 | 10 | 6.24 | 0.34 | 10 | 6.16 | 0.25 | 10 |
ALB (g/dL) | 4.09 | 0.28 | 10 | 4.05 | 0.31 | 10 | 3.98 | 0.18 | 10 |
GLO (g/dL) | 2.20 | 0.12 | 10 | 2.19 | 0.09 | 10 | 2.16 | 0.12 | 10 |
A/G Ratio | 1.86 | 0.16 | 10 | 1.86 | 0.12 | 10 | 1.83 | 0.12 | 10 |
TRG (mg/dL) | 58.20 | 11.75 | 10 | 68.40 | 14.41 | 10 | 66.00 | 13.52 | 10 |
CHO(mg/dL) | 75.96 | 17.61 | 10 | 71.76 | 9.11 | 10 | 66.56 | 14.39 | 10 |
ALT (U/L) | 38.10 | 18.88 | 10 | 27.30 | 2.87 | 10 | 28.30 | 3.40 | 10 |
AST (U/L) | 118.50 | 46.78 | 10 | 86.10 | 20.01 | 10 | 91.60 | 17.18 | 10 |
ALP (U/L) | 39.80 | 13.60 | 10 | 36.10 | 5.72 | 10 | 35.40 | 8.14 | 10 |
BUN (mg/dL) | 19.20 | 2.57 | 10 | 17.40 *- | 0.52 | 10 | 18.90 | 3.14 | 10 |
CRE (mg/dL) | 0.60 | 0.07 | 10 | 0.65 | 0.07 | 10 | 0.64 | 0.07 | 10 |
Na (mmol/L) | 145.20 | 1.32 | 10 | 146.40 | 1.43 | 10 | 145.90 | 3.25 | 10 |
K (mmol/L) | 4.35 | 0.27 | 10 | 4.06 *- | 0.24 | 10 | 4.03 *- | 0.12 | 10 |
Cl (mmol/L) | 115.90 | 2.38 | 10 | 116.70 | 2.45 | 10 | 116.70 | 3.47 | 10 |
Ca (mg/dL) | 11.31 | 0.32 | 10 | 11.28 | 0.33 | 10 | 11.19 | 0.28 | 10 |
P (mg/dL) | 5.80 | 0.64 | 10 | 5.51 | 0.59 | 10 | 5.75 | 0.76 | 10 |
HDL (mg/dL) | 50.52 | 11.63 | 10 | 48.62 | 5.17 | 10 | 46.00 | 10.25 | 10 |
Total bile acids (µmol/L) | 15.80 | 7.48 | 10 | 16.48 | 10.96 | 10 | 13.76 | 7.11 | 10 |
Urea (mg/dL) | 41.09 | 5.51 | 10 | 37.24 *- | 1.11 | 10 | 40.45 | 6.73 | 10 |
T3 (ng/dL) | 58.74 | 20.81 | 10 | 61.79 | 16.68 | 10 | 53.74 | 18.26 | 10 |
T4 (µg/dL) | 2.37 | 0.74 | 10 | 2.51 | 0.68 | 10 | 2.36 | 0.62 | 10 |
TSH (µIU/mL) | 1.34 | 1.08 | 10 | 1.20 | 1.09 | 10 | 1.43 | 1.46 | 10 |
Key: N = No. of Animals, *- = significantly low at p ≤0.05 as compared to G1
Note: The results of Bilirubin and LDL for majority of animals were below detectable range and hence mean and SD could not be calculated.
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 127.50 | 26.22 | 10 | 130.00 | 19.24 | 10 |
TP (g/dL) | 6.21 | 0.48 | 10 | 6.40 | 0.38 | 10 |
ALB (g/dL) | 4.00 | 0.46 | 10 | 4.16 | 0.32 | 10 |
GLO (g/dL) | 2.23 | 0.11 | 10 | 2.22 | 0.15 | 10 |
A/G Ratio | 1.79 | 0.23 | 10 | 1.89 | 0.16 | 10 |
TRG (mg/dL) | 71.40 | 24.98 | 10 | 95.80 **+ | 29.86 | 10 |
CHO(mg/dL) | 74.64 | 19.15 | 10 | 81.74 | 13.89 | 10 |
ALT (U/L) | 33.00 | 8.15 | 10 | 28.20 | 3.85 | 10 |
AST (U/L) | 99.70 | 33.37 | 10 | 89.30 | 38.13 | 10 |
ALP (U/L) | 38.20 | 4.61 | 10 | 43.50 | 4.90 | 10 |
BUN (mg/dL) | 17.00 | 2.16 | 10 | 16.10*- | 2.18 | 10 |
CRE (mg/dL) | 0.68 *+ | 0.06 | 10 | 0.59 | 0.07 | 10 |
Na (mmol/L) | 145.50 | 1.43 | 10 | 144.70 | 2.54 | 10 |
K (mmol/L) | 4.14 | 0.24 | 10 | 4.28 | 0.31 | 10 |
Cl (mmol/L) | 116.00 | 2.26 | 10 | 116.50 | 2.88 | 10 |
Ca (mg/dL) | 11.40 | 0.44 | 10 | 11.77*+ | 0.42 | 10 |
P (mg/dL) | 5.88 | 0.46 | 10 | 5.64 | 0.74 | 10 |
HDL (mg/dL) | 50.06 | 10.97 | 10 | 55.71 | 9.80 | 10 |
Total bile acids (µmol/L) | 18.73 | 10.96 | 10 | 10.37 | 7.28 | 10 |
Urea (mg/dL) | 36.38 | 4.62 | 10 | 34.45 *- | 4.67 | 10 |
T3 (ng/dL) | 59.18 | 10.97 | 10 | 64.20 | 14.86 | 10 |
T4 (µg/dL) | 2.44 | 0.59 | 10 | 2.57 | 0.75 | 10 |
TSH (µIU/mL) | 1.82 | 2.08 | 10 | 0.69 | 0.43 | 10 |
Key: N = No. of Animals, *+ or *- = significantly high or low at p ≤0.05 as compared to G1, **- = significantly low at p ≤0.01 as compared to G1, **+ = significantly high at p ≤0.01 as compared to G1
Note: The results of Bilirubin and LDL for majority of animals were below detectable range and hence mean and SD could not be calculated.
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
GLU (mg/dL) | 130.80 | 13.22 | 5 | 121.40 | 14.38 | 5 |
TP (g/dL) | 6.24 | 0.13 | 5 | 6.24 | 0.25 | 5 |
ALB (g/dL) | 3.96 | 0.13 | 5 | 3.82 | 0.16 | 5 |
GLO (g/dL) | 2.28 | 0.08 | 5 | 2.40 ↑ | 0.07 | 5 |
A/G Ratio | 1.72 | 0.11 | 5 | 1.58 | 0.08 | 5 |
TRG (mg/dL) | 77.40 | 28.26 | 5 | 67.60 | 6.39 | 5 |
CHO(mg/dL) | 59.03 | 7.33 | 5 | 79.73 ↑↑ | 5.36 | 5 |
ALT (U/L) | 27.80 | 3.11 | 5 | 27.20 | 6.57 | 5 |
AST (U/L) | 76.20 | 6.76 | 5 | 76.00 | 9.35 | 5 |
ALP (U/L) | 32.00 | 5.87 | 5 | 39.00 | 3.74 | 5 |
BUN (mg/dL) | 16.80 | 1.92 | 5 | 17.80 | 2.39 | 5 |
CRE (mg/dL) | 0.56 | 0.05 | 5 | 0.62 | 0.08 | 5 |
Na (mmol/L) | 138.00 | 1.41 | 5 | 138.60 | 0.55 | 5 |
K (mmol/L) | 3.90 | 0.25 | 5 | 4.02 | 0.08 | 5 |
Cl (mmol/L) | 112.20 | 1.64 | 5 | 116.00 ↑↑ | 1.22 | 5 |
Ca (mg/dL) | 10.86 | 0.25 | 5 | 10.84 | 0.18 | 5 |
P (mg/dL) | 4.48 | 0.67 | 5 | 4.68 | 0.22 | 5 |
HDL (mg/dL) | 38.07 | 4.79 | 5 | 48.87 ↑↑ | 3.90 | 5 |
Total bile acids (µmol/L) | 7.40 | 2.31 | 5 | 13.95 ↑ | 5.92 | 5 |
Urea (mg/dL) | 35.95 | 4.12 | 5 | 38.09 | 5.11 | 5 |
T3 (ng/dL) | 41.30 | 8.30 | 5 | 47.33 | 13.84 | 5 |
T4 (µg/dL) | 2.68 | 0.70 | 5 | 2.94 | 0.63 | 5 |
TSH (µIU/mL) | 0.52 | 0.25 | 5 | 0.54 | 0.20 | 5 |
Key: N = No. of Animals, = significantly high at p ≤0.05 as compared to G6, = significantly high at p ≤0.01 as compared to G6
Note: The results of Bilirubin and LDL for majority of animals were below detectable range and hence mean and SD could not be calculated
Summary of Urinalysis Parameters
Gender: Male No. of Animals/Group/Sex: 10
Parameters | Group & Dose (mg/kg b.w.) | |||||
G1 & 0 | G2 & 25 | G3 & 75 | ||||
Urine Volume (mL) | ||||||
Mean ± SD | 13.40 ± 4.55 | 12.44 ± 3.84 | 11.10 ± 2.73 | |||
Colour | ||||||
Light Yellow | 9 | 8 | 10 | |||
Yellow | 1 | 1 | - | |||
Appearance/Clarity | ||||||
Clear | 6 | 4 | 6 | |||
Slightly cloudy | 4 | 5 | 4 | |||
Specific Gravity | ||||||
Mean ± SD | 1.01 ± 0.00 | 1.02 ± 0.00 | 1.01 ± 0.00 | |||
Nitrite | ||||||
Negative | 6 | 4 | 8 | |||
Positive | 4 | 5 | 2 | |||
pH | ||||||
Mean ± SD | 7.05 ± 0.80 | 7.78 ± 1.03 | 7.20 ± 1.01 | |||
Protein (mg/dL) | ||||||
Negative | 6 | 3 | 5 | |||
10 | 1 | 1 | 2 | |||
30 | 1 | 1 | 3 | |||
100 | 2 | 4 | - | |||
Glucose (mg/dL) | ||||||
Negative | 10 | 9 | 10 | |||
Ketone bodies (mg/dL) | ||||||
Negative | 1 | 1 | 4 | |||
5 | 6 | 3 | 3 | |||
10 | 3 | 5 | 3 | |||
Urobilinogen (EU/dL) | ||||||
Normal | 10 | 9 | 10 | |||
Bilirubin (mg/dL) | ||||||
Negative | 10 | 9 | 10 | |||
Blood (RBC/µL) | ||||||
Negative | 10 | 9 | 10 | |||
Leu (WBC/µL) | ||||||
Negative | 3 | 1 | 1 | |||
10 | 3 | 5 | 5 | |||
25 | 3 | 3 | 4 | |||
75 | 1 | - | - |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G1 & 0 | G2 & 25 | G3 & 75 | ||||
Microscopy | ||||||
Epithelial Cells | ||||||
0 (0/hpf) | 9 | 5 | 7 | |||
1+ (1-2/hpf) | 1 | 4 | 3 | |||
Crystals | ||||||
1+ (1-5/hpf) | 5 | 1 | 1 | |||
2+ (5-10/hpf) | - | 2 | 6 | |||
3+ (10-15/hpf) | 5 | 2 | 2 | |||
4+ (>15/hpf) | - | 4 | 1 | |||
Leucocytes (W) | ||||||
0 (0/hpf) | 6 | 4 | 9 | |||
1+(1-2/hpf) | 4 | 5 | 1 | |||
Erythrocytes (R) | ||||||
0 (0/hpf) | 10 | 9 | 10 | |||
Other Abnormal Constituents (A) | ||||||
0(0/hpf) | 4 | 4 | 4 | |||
1+*(1-2/hpf) | 6 | 3 | 6 | |||
1+(1-2/hpf) | - | 1 | - | |||
2+*(3-4/hpf) | - | 1 | - | |||
Cast | ||||||
0(0/hpf) | 10 | 9 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |
G4 & 150 | G5 & 350 | |
Urine Volume (mL) | ||
Mean ± SD | 12.00 ± 3.00 | 12.60 ± 4.99 |
Colour | ||
Light Yellow | 9 | 9 |
Yellow | - | 1 |
Appearance | ||
Clear | 6 | 8 |
Slightly cloudy | 3 | 2 |
Specific Gravity | ||
Mean ± SD | 1.02 ± 0.01 | 1.01 ± 0.00 |
Nitrite | ||
Negative | 8 | 6 |
Positive | 1 | 4 |
pH | ||
Mean ± SD | 7.33 ± 1.00 | 8.50 ± 0.47 **+ |
Protein (mg/dL) | ||
Negative | 4 | 4 |
10 | 1 | 1 |
30 | 1 | 3 |
100 | 3 | 1 |
300 | - | 1 |
Glucose (mg/dL) | ||
Negative | 9 | 10 |
Ketone bodies (mg/dL) | ||
Negative | 2 | 5 |
5 | 2 | 2 |
10 | 5 | 3 |
Urobilinogen (EU/dL) | ||
Normal | 9 | 10 |
Bilirubin (mg/dL) | ||
Negative | 9 | 10 |
Blood (RBC/µL) | ||
Negative | 9 | 10 |
Leu (WBC/µL) | ||
Negative | 2 | 2 |
10 | 3 | 5 |
25 | 2 | 2 |
75 | 2 | 1 |
Parameters | Group & Dose (mg/kg b.w.) | |
G4 & 150 | G5 & 350 | |
Microscopy | ||
Epithelial Cells | ||
0 (0/hpf) | 8 | 8 |
1+ (1-2/hpf) | 1 | 2 |
Crystals | ||
1+ (1-5/hpf) | 2 | - |
2+ (5-10/hpf) | 3 | 1 |
3+(10-15/hpf) | 3 | 3 |
4+ (>15/hpf) | 1 | 6 |
Leucocytes (W) | ||
0 (0/hpf) | 4 | 3 |
1+(1-2/hpf) | 5 | 7 |
Erythrocytes (R) | ||
0 (0/hpf) | 9 | 10 |
Other Abnormal Constituents (A) | ||
0(0/hpf) | 5 | 4 |
1+*(1-2/hpf) | 4 | 4 |
1+(1-2/hpf) | - | 1 |
2+* | - | 1 |
Casts | ||
0(0/hpf) | 9 | 10 |
Key: hpf = high power field, * = Spermatozoa
Gender: Male No. of Animals/Group/Sex: 5
Parameters | Group & Dose (mg/kg b.w.) | |
G6 & 0 | G7 & 350 | |
Urine Volume (mL) | ||
Mean ± SD | 11.40 ± 3.29 | 19.20 ± 5.76↑ |
Colour | ||
Light Yellow | 5 | 5 |
Appearance | ||
Clear | 3 | 3 |
Slightly cloudy | 2 | 2 |
Specific Gravity | ||
Mean ± SD | 1.01 ± 0.00 | 1.02 ± 0.00 |
Nitrite | ||
Negative | 3 | 4 |
Positive | 2 | 1 |
pH | ||
Mean ± SD | 8.60 ± 0.55 | 7.90 ± 1.14 |
Protein (mg/dL) | ||
Negative | 3 | - |
10 | 1 | 3 |
30 | - | 1 |
100 | 1 | 1 |
Glucose (mg/dL) | ||
Negative | 5 | 5 |
Ketone bodies (mg/dL) | ||
Negative | 3 | 1 |
5 | 2 | 3 |
10 | - | 1 |
Urobilinogen (EU/dL) | ||
Normal | 5 | 5 |
Bilirubin (mg/dL) | ||
Negative | 5 | 5 |
Blood (RBC/µL) | ||
Negative | 5 | 5 |
Leu (WBC/µL) | ||
Negative | 3 | 1 |
10 | - | 2 |
25 | 2 | 2 |
Parameters | Group & Dose (mg/kg b.w.) | |
G6 & 0 | G7 & 350 | |
Microscopy | ||
Epithelial Cells | ||
0 (0/hpf) | 4 | 2 |
1+ (1-2/hpf) | 1 | 3 |
Crystals | ||
0(0/hpf) | 1 | 1 |
1+ (1-5/hpf) | 3 | 3 |
2+ (5-10/hpf) | 1 | 1 |
Leucocytes (W) | ||
0 (0/hpf) | 5 | 4 |
1+(1-2/hpf) | - | 1 |
Erythrocytes (R) | ||
0 (0/hpf) | 5 | 5 |
Other Abnormal Constituents (A) | ||
0(0/hpf) | 5 | 5 |
Casts | ||
0(0/hpf) | 2 | 1 |
1+ (1-5/hpf) | 2 | 3 |
2+ (5-10/hpf) | 1 | 1 |
Gender: Female No. of Animals/Group/Sex: 10
Parameters | Group & Dose (mg/kg b.w.) | |||||
G1 & 0 | G2 & 25 | G3 & 75 | ||||
Urine Volume (mL) | ||||||
Mean ± SD | 18.80 ± 7.67 | 18.00 ± 6.68 | 19.20 ± 7.80 | |||
Colour | ||||||
Light Yellow | 10 | 10 | 9 | |||
Yellow | - | - | 1 | |||
Appearance/Clarity | ||||||
Clear | 7 | 8 | 7 | |||
Slightly cloudy | 3 | 2 | 3 | |||
Specific Gravity | ||||||
Mean ± SD | 1.01 ± 0.00 | 1.01 ± 0.01 | 1.02 ± 0.00 (N=9) | |||
<=1.030 | - | - | 1/10 | |||
Nitrite | ||||||
Negative | 4 | 9 | 4 | |||
Positive | 6 | 1 | 6 | |||
pH | ||||||
Mean ± SD | 8.25 ± 0.79 | 7.25 ± 1.09 *- | 6.95 ± 1.07 **- | |||
Protein (mg/dL) | ||||||
Negative | 10 | 10 | 9 | |||
100 |
|
| 1 | |||
Glucose (mg/dL) | ||||||
Negative | 10 | 9 | 10 | |||
100 | - | 1 |
| |||
Ketone bodies (mg/dL) | ||||||
Negative | 10 | 10 | 10 | |||
5 |
|
|
| |||
Urobilinogen (EU/dL) | ||||||
Normal | 10 | 10 | 10 | |||
Bilirubin (mg/dL) | ||||||
Negative | 10 | 10 | 10 | |||
Blood (RBC/µL) | ||||||
Negative | 10 | 10 | 10 | |||
Leu (WBC/µL) | ||||||
Negative | 10 | 10 | 9 | |||
10 | - | - | 1 |
Key: *- = significantly high at p ≤0.05 as compared to G1, **- = significantly high at p ≤0.01 as compared to G1
Parameters | Group & Dose (mg/kg b.w.) | ||||
G1 & 0 | G2 & 25 | G3 & 75 | |||
Microscopy | |||||
Epithelial Cells | |||||
0 (0/hpf) | 9 | 9 | 8 | ||
1+ (1-2/hpf) | 1 | 1 | 2 | ||
Crystals | |||||
1+ (1-5/hpf) | 5 | 6 | 7 | ||
2+ (5-10/hpf) | - | 2 | - | ||
3+ (10-15/hpf) | 2 |
| 2 | ||
4+ (>15/hpf) | 3 | 2 | 1 | ||
Leucocytes (W) | |||||
0 (0/hpf) | 9 | 8 | 8 | ||
1+(1-2/hpf) | 1 | 2 | 2 | ||
Erythrocytes (R) | |||||
0 (0/hpf) | 10 | 10 | 10 | ||
Other Abnormal Constituents | |||||
0(0/hpf) | 10 | 10 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |
G4 & 150 | G5 & 350 | |
Urine Volume (mL) | ||
Mean ± SD | 23.10 ± 8.74 | 19.70 ± 7.20 |
Colour | ||
Light Yellow | 10 | 10 |
Appearance | ||
Clear | 7 | 8 |
Slightly cloudy | 3 | 2 |
Specific Gravity | ||
Mean ± SD | 1.01 ± 0.00 | 1.01 ± 0.00 |
Nitrite | ||
Negative | 4 | 5 |
Positive | 6 | 5 |
pH | ||
Mean ± SD | 7.30 ± 1.03 *- | 8.75 ± 0.35 |
Protein (mg/dL) | ||
Negative | 9 | 6 |
10 | - | 1 |
30 | - | 2 |
100 | 1 | 1 |
Glucose (mg/dL) | ||
Negative | 10 | 10 |
Ketone bodies (mg/dL) | ||
Negative | 10 | 10 |
Urobilinogen (EU/dL) | ||
Normal | 10 | 10 |
Bilirubin (mg/dL) | ||
Negative | 10 | 10 |
Blood (RBC/µL) | ||
Negative | 8 | 9 |
5 | 1 | 1 |
10 | 1 | - |
Leu (WBC/µL) | ||
Negative | 9 | 8 |
10 | - | 1 |
25 | 1 | 1 |
Key: *- = significantly high at p ≤0.05 as compared to G1
Parameters | Group & Dose (mg/kg b.w.) | |
G4 & 150 | G5 & 350 | |
Microscopy | ||
Epithelial Cells | ||
0 (0/hpf) | 9 | 10 |
1+ (1-2/hpf) | 1 | - |
Crystals | ||
1+ (1-5/hpf) | 5 | 2 |
2+ (5-10/hpf) | 3 | 2 |
3+ (10-15/hpf) | 1 | 1 |
4+ (>15/hpf) | 1 | 5 |
Leucocytes (W) | ||
0 (0/hpf) | 9 | 9 |
1+(1-2/hpf) | 1 | 1 |
Erythrocytes (R) | ||
0 (0/hpf) | 10 | 10 |
Other Abnormal Constituents (A) | ||
Nil | 10 | 10 |
Casts | ||
0 (0/hpf) | 10 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |
G6 & 0 | G7 & 350 | |
Urine Volume (mL) | ||
Mean ± SD | 14.00 ± 5.15 | 15.40 ± 2.70 |
Colour | ||
Light Yellow | 5 | 5 |
Appearance | ||
Clear | 5 | 5 |
Specific Gravity | ||
Mean ± SD | 1.01 ± 0.00 | 1.01 ± 0.00 |
Nitrite | ||
Negative | 3 | 3 |
Positive | 2 | 2 |
pH | ||
Mean ± SD | 8.30 ± 0.76 | 8.40 ± 0.55 |
Protein (mg/dL) | ||
Negative | 4 | 5 |
10 | 1 | - |
Glucose (mg/dL) | ||
Negative | 5 | 5 |
Ketone bodies (mg/dL) | ||
Negative | 5 | 5 |
Urobilinogen (EU/dL) | ||
Normal | 5 | 5 |
Bilirubin (mg/dL) | ||
Negative | 5 | 5 |
Blood (RBC/µL) | ||
Negative | 5 | 5 |
Leu (WBC/µL) | ||
Negative | 5 | 5 |
Parameters | Group & Dose (mg/kg b.w.) | |
G6 & 0 | G7 & 350 | |
Microscopy | ||
Epithelial Cells | ||
0 (0/hpf) | 2 | 4 |
1+ (1-2/hpf) | 3 | 1 |
Crystals | ||
0(0/hpf) | - | 1 |
1+ (1-5/hpf) | 5 | 4 |
Leucocytes (W) | ||
0 (0/hpf) | 5 | 2 |
1+(1-2/hpf) | - | 3 |
Erythrocytes (R) | ||
0 (0/hpf) | 5 | 5 |
Other Abnormal Constituents (A) | ||
0(0/hpf) | 3 | 2 |
1+ (1-5/hpf) | 2 | 3 |
Summary of Absolute Organ Weight (g)
Gender: Male
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 535.58 | 54.84 | 10 | 555.95 | 30.41 | 9 | 566.87 | 60.87 | 10 |
Adrenals | 0.0717 | 0.0108 | 10 | 0.0775 | 0.0057 | 9 | 0.0719 | 0.0079 | 10 |
Heart | 1.5903 | 0.1637 | 10 | 1.6907 | 0.0752 | 9 | 1.6192 | 0.1422 | 10 |
Brain | 2.1604 | 0.1634 | 10 | 2.2375 | 0.0783 | 9 | 2.1984 | 0.1440 | 10 |
Liver | 15.7950 | 2.0402 | 10 | 16.9435 | 0.8424 | 9 | 16.2539 | 2.1613 | 10 |
Thymus | 0.3095 | 0.0659 | 10 | 0.3378 | 0.0777 | 9 | 0.2800 | 0.0599 | 10 |
Lungs | 2.3101 | 0.4229 | 10 | 2.5017 | 0.6207 | 9 | 2.1007 | 0.2754 | 10 |
Kidneys | 3.4621 | 0.4637 | 10 | 3.7290 | 0.2813 | 9 | 3.5481 | 0.4357 | 10 |
Spleen | 0.9547 | 0.1824 | 10 | 0.9992 | 0.1821 | 9 | 1.0409 | 0.1964 | 10 |
Thyroid & parathyroid gland | 0.0298 | 0.0040 | 10 | 0.0302 | 0.0064 | 9 | 0.0324 | 0.0038 | 10 |
Pituitary gland | 0.0141 | 0.0024 | 10 | 0.0132 | 0.0025 | 9 | 0.0139 | 0.0012 | 10 |
Testes | 4.4119 | 1.0029 | 10 | 4.1513 | 0.3101 | 9 | 4.0648 | 0.2139 | 10 |
Epididymides | 1.5261 | 0.1960 | 10 | 1.6832 | 0.2377 | 9 | 1.5935 | 0.1436 | 10 |
Prostate + Seminal vesicles with coagulating glands | 3.1671 | 0.4558 | 10 | 3.5278 | 0.4532 | 9 | 3.5052 | 0.4755 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 532.27 | 41.02 | 9 | 519.68 | 43.01 | 10 |
Adrenals | 0.0694 | 0.0101 | 9 | 0.0746 | 0.0070 | 10 |
Heart | 1.5509 | 0.1731 | 9 | 1.5296 | 0.1333 | 10 |
Brain | 2.1773 | 0.1368 | 9 | 2.1959 | 0.1209 | 10 |
Liver | 16.2525 | 2.6461 | 9 | 16.2705 | 2.5194 | 10 |
Thymus | 0.3555 | 0.0694 | 9 | 0.3023 | 0.1031 | 10 |
Lungs | 2.1881 | 0.5015 | 9 | 2.1901 | 0.3364 | 10 |
Kidneys | 3.4915 | 0.2802 | 9 | 3.4773 | 0.2991 | 10 |
Spleen | 1.0166 | 0.2100 | 9 | 1.0029 | 0.1427 | 10 |
Thyroid & parathyroid gland | 0.0307 | 0.0042 | 9 | 0.0316 | 0.0063 | 10 |
Pituitary gland | 0.0134 | 0.0019 | 9 | 0.0136 | 0.0008 | 10 |
Testes | 4.3310 | 1.0704 | 9 | 3.9988 | 0.2779 | 10 |
Epididymides | 1.5470 | 0.2330 | 9 | 1.6937 | 0.2346 | 10 |
Prostate + Seminal vesicles with coagulating glands | 3.4367 | 0.2823 | 9 | 3.2567 | 0.5621 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 538.85 | 38.08 | 5 | 585.82 | 46.59 | 5 |
Adrenals | 0.0613 | 0.0079 | 5 | 0.0783 ↑↑ | 0.0062 | 5 |
Heart | 1.5328 | 0.1331 | 5 | 1.7112 | 0.1429 | 5 |
Brain | 2.2654 | 0.1048 | 5 | 2.2796 | 0.0682 | 5 |
Liver | 16.2545 | 2.6403 | 5 | 18.1434 | 2.3783 | 5 |
Thymus | 0.3722 | 0.1547 | 5 | 0.4774 | 0.2768 | 5 |
Lungs | 2.0333 | 0.2463 | 5 | 2.4074 | 0.5404 | 5 |
Kidneys | 3.4059 | 0.2255 | 5 | 3.7194 ↑ | 0.1603 | 5 |
Spleen | 0.8864 | 0.1558 | 5 | 1.0839 | 0.2516 | 5 |
Thyroid & parathyroid gland | 0.0431 | 0.0037 | 5 | 0.0453 | 0.0022 | 5 |
Pituitary gland | 0.0181 | 0.0040 | 5 | 0.0203 | 0.0009 | 5 |
Testes | 4.1354 | 0.3255 | 5 | 4.7030 | 0.6757 | 5 |
Epididymides | 1.5524 | 0.1296 | 5 | 1.7272 | 0.1535 | 5 |
Prostate + Seminal vesicles with coagulating glands | 3.7056 | 0.1763 | 5 | 4.2455 ↑ | 0.4182 | 5 |
Key: N = No. of Animals, = significantly high at p ≤0.05 as compared to G6, = significantly high at p ≤0.01 as compared to G6
Gender: Female
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 283.81 | 23.49 | 10 | 287.95 | 22.26 | 10 | 291.46 | 25.10 | 10 |
Adrenals | 0.0949 | 0.0131 | 10 | 0.0941 | 0.0092 | 10 | 0.0948 | 0.0116 | 10 |
Heart | 0.9761 | 0.1058 | 10 | 0.9971 | 0.0651 | 10 | 1.0068 | 0.0698 | 10 |
Brain | 2.0215 | 0.1350 | 10 | 2.0392 | 0.1293 | 10 | 2.0322 | 0.0860 | 10 |
Liver | 9.1084 | 1.7731 | 10 | 9.2187 | 1.2790 | 10 | 9.4593 | 1.7691 | 10 |
Thymus | 0.3256 | 0.0546 | 10 | 0.3268 | 0.0938 | 10 | 0.3197 | 0.0590 | 10 |
Lungs | 1.7148 | 0.3918 | 10 | 2.2858 | 0.8802 | 10 | 2.0765 | 1.0813 | 10 |
Kidneys | 1.9401 | 0.2188 | 10 | 2.0218 | 0.2004 | 10 | 1.9487 | 0.1447 | 10 |
Spleen | 0.6860 | 0.0789 | 10 | 0.7286 | 0.1355 | 10 | 0.7278 | 0.1363 | 10 |
Thyroid & parathyroid gland | 0.0333 | 0.0051 | 10 | 0.0324 | 0.0049 | 10 | 0.0358 | 0.0069 | 10 |
Pituitary gland | 0.0166 | 0.0042 | 10 | 0.0156 | 0.0025 | 10 | 0.0178 | 0.0020 | 10 |
Ovaries | 0.1703 | 0.0407 | 10 | 0.1740 | 0.0295 | 10 | 0.1861 | 0.0243 | 10 |
Uterus With Cervix | 0.8594 | 0.1955 | 10 | 0.8988 | 0.2890 | 10 | 0.8386 | 0.1534 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 290.34 | 26.07 | 10 | 314.68 | 29.23 | 10 |
Adrenals | 0.0992 | 0.0109 | 10 | 0.1000 | 0.0191 | 10 |
Heart | 1.0288 | 0.1166 | 10 | 1.0333 | 0.0602 | 10 |
Brain | 1.9816 | 0.0996 | 10 | 1.9867 | 0.1068 | 10 |
Liver | 10.2137 | 1.7890 | 10 | 10.3750 | 2.0584 | 10 |
Thymus | 0.3453 | 0.0776 | 10 | 0.3687 | 0.0633 | 10 |
Lungs | 2.0250 | 0.8353 | 10 | 2.1813 | 1.1673 | 10 |
Kidneys | 2.0794 | 0.2028 | 10 | 2.1206 | 0.2829 | 10 |
Spleen | 0.7289 | 0.1188 | 10 | 0.6857 | 0.1094 | 10 |
Thyroid & parathyroid gland | 0.0293 | 0.0037 | 10 | 0.0363 | 0.0043 | 10 |
Pituitary gland | 0.0171 | 0.0035 | 10 | 0.0180 | 0.0034 | 10 |
Ovaries | 0.1757 | 0.0258 | 10 | 0.1725 | 0.0158 | 10 |
Uterus With Cervix | 0.7545 | 0.1607 | 10 | 0.7457 | 0.1612 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Terminal Body Weight | 278.21 | 13.85 | 5 | 296.37 | 19.35 | 5 |
Adrenals | 0.0984 | 0.0114 | 5 | 0.0886 | 0.0115 | 5 |
Heart | 1.0666 | 0.0724 | 5 | 1.0354 | 0.0809 | 5 |
Brain | 2.1188 | 0.0870 | 5 | 2.1277 | 0.1737 | 5 |
Liver | 9.1984 | 0.6984 | 5 | 8.7385 | 0.6148 | 5 |
Thymus | 0.2971 | 0.0412 | 5 | 0.3822 | 0.0833 | 5 |
Lungs | 1.7501 | 0.4023 | 5 | 1.6007 | 0.2190 | 5 |
Kidneys | 1.9079 | 0.0305 | 5 | 1.9734 | 0.1472 | 5 |
Spleen | 0.6183 | 0.0561 | 5 | 0.7034 | 0.0861 | 5 |
Thyroid & parathyroid gland | 0.0418 | 0.0060 | 5 | 0.0328 ↓↓ | 0.0032 | 5 |
Pituitary gland | 0.0187 | 0.0016 | 5 | 0.0171 | 0.0015 | 5 |
Ovaries | 0.1852 | 0.0682 | 5 | 0.1708 | 0.0164 | 5 |
Uterus With Cervix | 0.6583 | 0.1979 | 5 | 0.5827 | 0.1437 | 5 |
Key: N = No. of Animals, ↓↓ = significantly high at p ≤0.01 as compared to G6
Summary of Relative Organ Weight (%)
Gender: Male
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0135 | 0.0019 | 10 | 0.0140 | 0.0011 | 9 | 0.0128 | 0.0017 | 10 |
Heart | 0.2976 | 0.0208 | 10 | 0.3049 | 0.0205 | 9 | 0.2871 | 0.0235 | 10 |
Brain | 0.4050 | 0.0245 | 10 | 0.4035 | 0.0262 | 9 | 0.3901 | 0.0308 | 10 |
Liver | 2.9451 | 0.1663 | 10 | 3.0532 | 0.1865 | 9 | 2.8637 | 0.1947 | 10 |
Thymus | 0.0585 | 0.0146 | 10 | 0.0610 | 0.0140 | 9 | 0.0499 | 0.0118 | 10 |
Lungs | 0.4344 | 0.0840 | 10 | 0.4511 | 0.1113 | 9 | 0.3706 | 0.0325 | 10 |
Kidneys | 0.6465 | 0.0555 | 10 | 0.6718 | 0.0542 | 9 | 0.6261 | 0.0455 | 10 |
Spleen | 0.1778 | 0.0260 | 10 | 0.1808 | 0.0371 | 9 | 0.1837 | 0.0289 | 10 |
Pituitary gland | 0.0026 | 0.0004 | 10 | 0.0024 | 0.0005 | 9 | 0.0025 | 0.0003 | 10 |
Thyroid & parathyroid gland | 0.0056 | 0.0010 | 10 | 0.0054 | 0.0012 | 9 | 0.0058 | 0.0010 | 10 |
Testes | 0.8214 | 0.1515 | 10 | 0.7489 | 0.0705 | 9 | 0.7232 | 0.0726 | 10 |
Epididymides | 0.2850 | 0.0233 | 10 | 0.3038 | 0.0487 | 9 | 0.2833 | 0.0337 | 10 |
Prostate + Seminal vesicles with coagulating glands | 0.5934 | 0.0873 | 10 | 0.6379 | 0.1022 | 9 | 0.6275 | 0.1255 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0130 | 0.0016 | 9 | 0.0144 | 0.0015 | 10 |
Heart | 0.2911 | 0.0178 | 9 | 0.2948 | 0.0207 | 10 |
Brain | 0.4116 | 0.0451 | 9 | 0.4238 | 0.0234 | 10 |
Liver | 3.0434 | 0.3220 | 9 | 3.1324 | 0.4396 | 10 |
Thymus | 0.0674 | 0.0161 | 9 | 0.0574 | 0.0150 | 10 |
Lungs | 0.4090 | 0.0709 | 9 | 0.4253 | 0.0826 | 10 |
Kidneys | 0.6571 | 0.0439 | 9 | 0.6697 | 0.0349 | 10 |
Spleen | 0.1902 | 0.0326 | 9 | 0.1928 | 0.0197 | 10 |
Pituitary gland | 0.0025 | 0.0004 | 9 | 0.0026 | 0.0003 | 10 |
Thyroid & parathyroid gland | 0.0058 | 0.0007 | 9 | 0.0061 | 0.0013 | 10 |
Testes | 0.8180 | 0.2039 | 9 | 0.7726 | 0.0672 | 10 |
Epididymides | 0.2928 | 0.0529 | 9 | 0.3258 | 0.0355 | 10 |
Prostate + Seminal vesicles with coagulating glands | 0.6484 | 0.0654 | 9 | 0.6325 | 0.1237 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0114 | 0.0010 | 5 | 0.0135 | 0.0020 | 5 |
Heart | 0.2847 | 0.0187 | 5 | 0.2922 | 0.0131 | 5 |
Brain | 0.4214 | 0.0222 | 5 | 0.3916 | 0.0405 | 5 |
Liver | 3.0004 | 0.2964 | 5 | 3.0900 | 0.2037 | 5 |
Thymus | 0.0690 | 0.0270 | 5 | 0.0802 | 0.0428 | 5 |
Lungs | 0.3788 | 0.0528 | 5 | 0.4085 | 0.0659 | 5 |
Kidneys | 0.6324 | 0.0147 | 5 | 0.6374 | 0.0474 | 5 |
Spleen | 0.1641 | 0.0249 | 5 | 0.1845 | 0.0356 | 5 |
Pituitary gland | 0.0033 | 0.0005 | 5 | 0.0035 | 0.0004 | 5 |
Thyroid & parathyroid gland | 0.0080 | 0.0004 | 5 | 0.0078 | 0.0007 | 5 |
Testes | 0.7709 | 0.0840 | 5 | 0.8072 | 0.1319 | 5 |
Epididymides | 0.2889 | 0.0277 | 5 | 0.2961 | 0.0342 | 5 |
Prostate + Seminal vesicles with coagulating glands | 0.6904 | 0.0586 | 5 | 0.7242 | 0.0254 | 5 |
Gender: Female
Parameters | Group & Dose (mg/kg b.w.) | ||||||||
G1 & 0 | G2 & 25 | G3 & 75 | |||||||
Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0335 | 0.0045 | 10 | 0.0329 | 0.0042 | 10 | 0.0326 | 0.0031 | 10 |
Heart | 0.3446 | 0.0328 | 10 | 0.3472 | 0.0226 | 10 | 0.3466 | 0.0243 | 10 |
Brain | 0.7156 | 0.0659 | 10 | 0.7112 | 0.0628 | 10 | 0.7023 | 0.0704 | 10 |
Liver | 3.1993 | 0.4497 | 10 | 3.1999 | 0.3539 | 10 | 3.2307 | 0.3996 | 10 |
Thymus | 0.1152 | 0.0211 | 10 | 0.1133 | 0.0303 | 10 | 0.1097 | 0.0176 | 10 |
Lungs | 0.6033 | 0.1229 | 10 | 0.7902 | 0.2823 | 10 | 0.6999 | 0.3174 | 10 |
Kidneys | 0.6839 | 0.0575 | 10 | 0.7019 | 0.0403 | 10 | 0.6706 | 0.0466 | 10 |
Spleen | 0.2418 | 0.0197 | 10 | 0.2540 | 0.0502 | 10 | 0.2500 | 0.0428 | 10 |
Pituitary gland | 0.0058 | 0.0011 | 10 | 0.0054 | 0.0009 | 10 | 0.0061 | 0.0008 | 10 |
Thyroid & parathyroid gland | 0.0118 | 0.0022 | 10 | 0.0112 | 0.0014 | 10 | 0.0123 | 0.0024 | 10 |
Ovaries | 0.0599 | 0.0128 | 10 | 0.0606 | 0.0106 | 10 | 0.0644 | 0.0108 | 10 |
Uterus With Cervix | 0.3022 | 0.0590 | 10 | 0.3120 | 0.0932 | 10 | 0.2905 | 0.0640 | 10 |
Parameters | Group & Dose (mg/kg b.w.) | |||||
G4 & 150 | G5 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0344 | 0.0046 | 10 | 0.0316 | 0.0042 | 10 |
Heart | 0.3545 | 0.0252 | 10 | 0.3305 | 0.0315 | 10 |
Brain | 0.6858 | 0.0481 | 10 | 0.6357 *- | 0.0597 | 10 |
Liver | 3.5109 | 0.4465 | 10 | 3.2846 | 0.4869 | 10 |
Thymus | 0.1181 | 0.0190 | 10 | 0.1181 | 0.0234 | 10 |
Lungs | 0.6944 | 0.2591 | 10 | 0.6811 | 0.3185 | 10 |
Kidneys | 0.7168 | 0.0366 | 10 | 0.6743 | 0.0704 | 10 |
Spleen | 0.2517 | 0.0398 | 10 | 0.2173 | 0.0229 | 10 |
Pituitary gland | 0.0059 | 0.0009 | 10 | 0.0057 | 0.0010 | 10 |
Thyroid & parathyroid gland | 0.0101 | 0.0011 | 10 | 0.0116 | 0.0013 | 10 |
Ovaries | 0.0615 | 0.0136 | 10 | 0.0551 | 0.0063 | 10 |
Uterus With Cervix | 0.2610 | 0.0567 | 10 | 0.2382 | 0.0513 | 10 |
Key: N = No. of Animals, *- = significantly low at p ≤0.05 as compared to G1
Parameters | Group & Dose (mg/kg b.w.) | |||||
G6 & 0 | G7 & 350 | |||||
Mean | SD | N | Mean | SD | N | |
Adrenals | 0.0353 | 0.0028 | 5 | 0.0301 | 0.0054 | 5 |
Heart | 0.3838 | 0.0264 | 5 | 0.3492 ↓ | 0.0115 | 5 |
Brain | 0.7626 | 0.0382 | 5 | 0.7182 | 0.0391 | 5 |
Liver | 3.3163 | 0.3358 | 5 | 2.9531 | 0.1941 | 5 |
Thymus | 0.1071 | 0.0164 | 5 | 0.1283 | 0.0226 | 5 |
Lungs | 0.6268 | 0.1277 | 5 | 0.5416 | 0.0781 | 5 |
Kidneys | 0.6874 | 0.0418 | 5 | 0.6656 | 0.0154 | 5 |
Spleen | 0.2234 | 0.0300 | 5 | 0.2368 | 0.0177 | 5 |
Pituitary gland | 0.0067 | 0.0008 | 5 | 0.0058 | 0.0006 | 5 |
Thyroid & parathyroid gland | 0.0151 | 0.0028 | 5 | 0.0111↓ | 0.0016 | 5 |
Ovaries | 0.0670 | 0.0252 | 5 | 0.0580 | 0.0090 | 5 |
Uterus With Cervix | 0.2369 | 0.0732 | 5 | 0.1978 | 0.0537 | 5 |
Key: N = No. of Animals, ↓ = significantly low at p ≤0.05 as compared to G6
Summary of Vaginal Smear Examination
Gender: Female
Observation | Group & Dose (mg/kg b.w.) | ||||
No. of animals | |||||
G1 & 0 | G2 & 25 | G3 & 75 | G4 & 150 | G5 & 30 | |
Proestrus | 6 | 6 | 4 | 2 | 3 |
Estrus | 3 | 3 | 2 | 4 | 6 |
Metestrus | - | 1 | 4 | 4 | 1 |
Diestrus | 1 | - | - | - | - |
Observation | Group & Dose (mg/kg b.w.) | |
No. of animals | ||
G6 & 0 | G7 & 350 | |
Proestrus | 1 | 3 |
Estrus | 1 | - |
Metestrus | 1 | 2 |
Diestrus | 2 | - |
Summary of Gross Pathology Findings
Gender: Male
Gross Pathology observation (s) | Number of animals with or without lesion (s)/ Numbers of animals observed | ||||||
G1 | G2 | G3 | G4 | G5 | G6 | G7 | |
Seminal vesicle – Small, unilateral | 1/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/5 | 0/5 |
Gastro intestinal tract – Distended and empty | 0/10 | 1/10# | 0/10 | 1/10# | 0/10 | 0/5 | 0/5 |
Testes – Enlarged, bilateral | 0/10 | 0/10 | 0/10 | 1/10 | 0/10 | 0/5 | 0/5 |
No Abnormality Detected | 9/10 | 9/10 | 10/10 | 8/10 | 10/10 | 5/5 | 5/5 |
Gender: Female
Gross Pathology observation (s) | Number of animals with or without lesion (s)/ Numbers of animals observed | ||||||
G1 | G2 | G3 | G4 | G5 | G6 | G7 | |
No Abnormality Detected | 10/10 | 10/10 | 10/10 | 10/10 | 10/10 | 5/5 | 5/5 |
Summary of Histopathology Findings
Gender: Male
Organs/ Histopathology | No. of tissues showing lesion / no. of tissues examined | ||||||
Group & Dose (mg/kg b.w.) | |||||||
G1 (0) | G2* (25) | G3* (75) | G4* (150) | G5 (350) | G6* (0) | G7* (350) | |
LIVER (N) | 8/10 | 1/1# | - | 0/1# | 9/10 | - | - |
Infiltrate, mononuclear cell, multifocal | 2/10 | - | - | 0/1# | 1/10 | - | - |
Infiltrate, poly morpho mononuclear cell, multifocal | 0/10 | - | - | 1/1# | 0/10 | - | - |
LUNGS (with bronchi and bronchiole) (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
KIDNEYS (N) | 7/10 | 8/10 | 4/10 | 5/10 | 6/10 | 4/5 | 2/5 |
Cast, focal, bilateral | 2/10 | 0/10 | 0/10 | 1/10 | 2/10 | 0/5 | 0/5 |
Cast, focal, unilateral | 0/10 | 2/10 | 2/10 | 1/10 | 4/10 | 1/5 | 2/5 |
Basophilia, tubule, focal, bilateral | 0/10 | 0/10 | 0/10 | 1/10 | 0/10 | 0/5 | 0/5 |
Basophilia, tubule, focal, unilateral | 1/10 | 0/10 | 3/10 | 2/10# | 2/10 | 1/5 | 1/5 |
Basophilia, tubule, multifocal, bilateral | 0/10 | 0/10 | 1/10 | 0/10 | 0/10 | 0/5 | 0/5 |
Necrosis, multifocal, bilateral | 0/10 | 1/10# | 0/10 | 0/10 | 1/10 | 0/5 | 0/5 |
Infiltrate, inflammatory cell, focal, cortex, unilateral | 0/10 | 0/10 | 0/10 | 1/10 | 0/10 | 0/5 | 0/5 |
URINARY BLADDER (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SPLEEN (N) | 10/10 | 0/1# | - | 1/1# | 10/10 | - | - |
Atrophy | 0/10 | 1/1# | - | 0/1# | 0/10 | - | - |
EMH, multifocal | 0/10 | 0/1# | - | 0/1# | 0/10 | - | - |
THYMUS (N) | 10/10 | 0/1# | - | 1/1# | 9/10 | - | - |
Atrophy | 0/10 | 1/1# | - | 0/1# | 0/10 | - | - |
Ectopic tissue, focal | 0/10 | 0/1# | - | 0/1# | 1/10 | - | - |
MESENTERIC LYMPHNODES (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
PITUITARY GLAND (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
Key: N = within normal histological limit; * = only target organs (Stomach, trachea and kidneys) were evaluated; # = Found dead animal.
Organs/ Histopathology | No. of tissues showing lesion / no. of tissues examined | ||||||
Group & Dose (mg/kg b.w.) | |||||||
G1 (0) | G2* (25) | G3* (75) | G4* (150) | G5 (350) | G6* (0) | G7* (350) | |
TESTES (N) | 8/10 | 1/1# | - | 1/1# | 9/10 | - | - |
Dilatation, tubule, multifocal, unilateral | 2/10 | 0/1# | - | 1/1$ | 0/10 | - | - |
Dilatation, tubule, multifocal, bilateral | 0/10 | 1/1$ | - | 0/1# | 0/10 | - | - |
Degeneration, tubule, multifocal, unilateral | 0/10 | 0/1# | - | 0/1# | 1/10 | - | - |
ADRENAL GLANDS (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
EPIDIDYMIDES (N) | 10/10 | 1/1#$ | - | 1/1#$ | 9/10 | - | - |
Cell debris, lumen, multifocal, unilateral | 0/10 | 0/1# | - | 0/1# | 1/10 | - | - |
PROSTATE (N) | 7/10 | 1/1# | - | 1/1# | 10/10 | - | - |
Atrophy, diffuse | 1/10 | 0/1# | - | 0/1# | 10/10 | - | - |
Infiltrate, inflammatory cell, multifocal | 2/10 | 0/1# | - | 0/1# | 10/10 | - | - |
SEMINAL VESICLES (with coagulating glands) (N) | 9/10 | 1/1# | - | 1/1# | 10/10 | - | - |
Atrophy, diffuse, unilateral | 1/10 | 0/1# | - | 0/1# | 0/10 | - | - |
HEART (N) | 10/10 | 1/1# | - | 1/1# | 9/10 | - | - |
Infiltrate, inflammatory cell, multifocal | 0/10 | 0/1# | - | 0/1# | 1/10 | - | - |
AORTA (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SALIVARY GLANDS (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
MANDIBULAR LYMPHNODES (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
ESOPHAGUS (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
TRACHEA (N) | 10/10 | 10/10 | 10/10 | 8/10 | 9/10 | 3/5 | 5/5 |
Erosion, diffuse | 0/10 | 0/1# | - | 1/1# | 0/10 | - | - |
Infiltration, MNC/PMNC, diffuse | 0/10 | 0/10 | 0/10 | 1/10 | 1/10 | 2/5 | 0/5 |
Key: N = within normal histological limit; MNC/PMNC = Mono nuclear cell/poly morpho nuclear cell; * = only target organs (Stomach, trachea and kidneys) were evaluated; # = Found dead animal; $ = Gross pathology organ
Organs/ Histopathology | No. of tissues showing lesion / no. of tissues examined | ||||||
Group & Dose (mg/kg b.w.) | |||||||
G1 (0) | G2* (25) | G3* (75) | G4* (150) | G5 (350) | G6* (0) | G7* (350) | |
THYROID (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
PARATHYROID (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
STOMACH (N) | 10/10 | 10/10 | 9/10 | 10/10 | 8/10 | 5/5 | 5/5 |
Hyperplasia, squamous cell – Nonglandular stomach, diffuse | 0/10 | 0/10 | 0/10 | 0/10 | 1/10 | 0/5 | 0/5 |
Inflammation – Nonglandular stomach, diffuse | 0/10 | 0/10 | 0/10 | 0/10 | 2/10 | 0/5 | 0/5 |
PANCREAS (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
DUODENUM (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
JEJUNUM (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
ILEUM (with peyer's patches) (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
CECUM (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
COLON (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
RECTUM (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
BRAIN (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SCIATIC NERVE (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
EYES (with optic nerve) (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SKIN (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
MAMMARY GLANDS (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SKELETAL MUSCLE (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
SPINAL CORD (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
FEMUR WITH JOINT (N) | 10/10 | 1/1# | - | 1/1# | 10/10 | - | - |
Key: N = within normal histological limit; * = only target organs (Stomach, trachea and kidneys) were evaluated; # = Found dead animal.
Gender: Female
Organs/ Histopathology | No. of tissues showing lesion / no. of tissues examined | ||||||
Group & Dose (mg/kg b.w.) | |||||||
G1 (0) | G2* (25) | G3* (75) | G4* (150) | G5 (350) | G6* (0) | G7* (350) | |
LIVER (N) | 10/10 | - | - | - | 10/10 | - | - |
LUNGS (with bronchi and bronchiole) (N) | 10/10 | - | - | - | 10/10 | - | - |
KIDNEYS (N) | 9/10 | 7/10 | 9/10 | 10/10 | 8/10 | 5/5 | 5/5 |
Cast, focal, unilateral | 0/10 | 2/10 | 1/10 | 0/10 | 1/10 | 0/5 | 0/5 |
Cast, multifocal, bilateral | 0/10 | 0/10 | 0/10 | 0/10 | 1/10 | 0/5 | 0/5 |
Basophilia, tubule, focal, unilateral | 0/10 | 1/10 | 0/10 | 0/10 | 0/10 | 0/5 | 0/5 |
Infiltrate, inflammatory cell, multifocal, urethelium, bilateral | 1/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/5 | 0/5 |
URINARY BLADDER (N) | 10/10 | - | - | - | 10/10 | - | - |
SPLEEN (N) | 9/10 | - | - | - | 9/10 | - | - |
EMH, multifocal | 1/10 | - | - | - | 1/10 | - | - |
THYMUS (N) | 10/10 | - | - | - | 9/10 | - | - |
Ectopic tissue, focal | 0/10 | - | - | - | 1/10 | - | - |
MESENTERIC LYMPHNODES (N) | 10/10 | - | - | - | 10/10 | - | - |
PITUITARY GLAND (N) | 10/10 | - | - | - | 10/10 | - | - |
OVARIES (N) | 10/10 | - | - | - | 10/10 | - | - |
ADRENAL GLANDS (N) | 10/10 | - | - | - | 10/10 | - | - |
UTERUS (with cervix and vagina) (N) | 10/10 | - | - | - | 10/10 | - | - |
HEART (N) | 10/10 | - | - | - | 10/10 | - | - |
AORTA (N) | 10/10 | - | - | - | 10/10 | - | - |
SALIVARY GLANDS (N) | 10/10 | - | - | - | 10/10 | - | - |
MANDIBULAR LYMPHNODES (N) | 10/10 | - | - | - | 10/10 | - | - |
ESOPHAGUS (N) | 10/10 | - | - | - | 10/10 | - | - |
Key: N = within normal histological limit; * = only target organs (Stomach, trachea and kidneys) were evaluated
Organs/ Histopathology | No. of tissues showing lesion / no. of tissues examined | ||||||
Group & Dose (mg/kg b.w.) | |||||||
G1 (0) | G2* (25) | G3* (75) | G4* (150) | G5 (350) | G6* (0) | G7* (350) | |
TRACHEA (N) | 10/10 | 8 | 10/10 | 10/10 | 10/10 | 5/5 | 5/5 |
Infiltration, MNC/PMNC, diffuse | 0/10 | 2 | 0/10 | 0/10 | 0/10 | 0/5 | 0/5 |
THYROID (N) | 10/10 | - | - | - | 10/10 | - | - |
PARATHYROID (N) | 10/10 | - | - | - | 10/10 | - | - |
STOMACH (N) | 10/10 | 10/10 | 10/10 | 10/10 | 10/10 | 5/5 | 5/5 |
PANCREAS (N) | 10/10 | - | - | - | 10/10 | - | - |
DUODENUM (N) | 10/10 | - | - | - | 10/10 | - | - |
JEJUNUM (N) | 10/10 | - | - | - | 10/10 | - | - |
ILEUM (with peyer's patches) (N) | 10/10 | - | - | - | 10/10 | - | - |
CECUM (N) | 10/10 | - | - | - | 10/10 | - | - |
COLON (N) | 10/10 | - | - | - | 10/10 | - | - |
RECTUM (N) | 10/10 | - | - | - | 10/10 | - | - |
BRAIN (N) | 10/10 | - | - | - | 10/10 | - | - |
SCIATIC NERVE (N) | 10/10 | - | - | - | 10/10 | - | - |
EYES (with optic nerve) (N) | 10/10 | - | - | - | 10/10 | - | - |
SKIN (N) | 10/10 | - | - | - | 10/10 | - | - |
MAMMARY GLANDS (N) | 10/10 | - | - | - | 10/10 | - | - |
SKELETAL MUSCLE (N) | 10/10 | - | - | - | 10/10 | - | - |
SPINAL CORD (N) | 10/10 | - | - | - | 10/10 | - | - |
FEMUR WITH JOINT (N) | 10/10 | - | - | - | 10/10 | - | - |
Key: N = within normal histological limit; * = only target organs (Stomach, trachea and kidneys) were evaluated; MNC/PMNC = Mono nuclear cell/ Poly morpho nuclear cell
Results of Dose Formulation Analysis
Formulation Analysis - Pre-Dose
Group | Nominal concentration (mg/ml) | Found Concentration (mg/ml) | Average (mg/ml) | Observed Concentration (%) | Average (%) | SD | Deviation (%) | |
G1 & G6 | 0.0 | - | - | - | - | - | - | - |
G2 | 5.0 | Top | 5.0009 | 4.7503 | 99.9 | 94.9 | 4.3405 | -5.4 |
Mid | 4.6402 | 92.7 | ||||||
Bottom | 4.6098 | 92.1 | ||||||
G3 | 15.0 | Top | 14.3155 | 14.2758 | 95.4 | 95.2 | 1.6623 | -5.1 |
Mid | 14.5083 | 96.7 | ||||||
Bottom | 14.0037 | 93.4 | ||||||
G4 | 30.0 | Top | 28.0970 | 29.7599 | 93.6 | 99.2 | 4.8590 | -0.8 |
Mid | 30.6789 | 102.3 | ||||||
Bottom | 30.5040 | 101.7 | ||||||
G5 & G7 | 70.0 | Top | 71.7697 | 72.4562 | 102.5 | 103.5 | 0.9165 | 3.4 |
Mid | 73.0347 | 104.3 | ||||||
Bottom | 72.5641 | 103.7 |
Formulation Analysis - 6th Week
Group | Nominal concentration (mg/ml) | Found Concentration (mg/ml) | Average (mg/ml) | Observed Concentration (%) | Average (%) | SD | Deviation (%) | |
G1 & G6 | 0.0 | - | - | - | - | - | - | - |
G2 | 5.0 | Top | 4.9834 | 5.0111 | 99.6 | 100.2 | 0.6658 | 0.2 |
Mid | 5.0033 | 100.0 | ||||||
Bottom | 5.0464 | 100.9 | ||||||
G3 | 15.0 | Top | 15.4202 | 15.5604 | 102.8 | 103.7 | 1.0693 | 3.6 |
Mid | 15.5313 | 103.5 | ||||||
Bottom | 15.7296 | 104.9 | ||||||
G4 | 30.0 | Top | 31.8328 | 31.7250 | 106.1 | 105.7 | 0.3215 | 5.4 |
Mid | 31.6800 | 105.6 | ||||||
Bottom | 31.6622 | 105.5 | ||||||
G5 & G7 | 70.0 | Top | 71.2798 | 71.5079 | 101.8 | 102.1 | 1.2342 | 2.1 |
Mid | 70.7613 | 101.1 | ||||||
Bottom | 72.4826 | 103.5 |
Formulation Analysis - 13th Week
Group | Nominal concentration (mg/ml) | Found Concentration (mg/ml) | Average (mg/ml) | Observed Concentration (%) | Average (%) | SD | Deviation (%) | |
G1 & G6 | 0.0 | - | - | - | - | - | - | - |
G2 | 5.0 | Top | 5.0273 | 5.0282 | 100.5 | 100.5 | 0.0577 | 0.5 |
Mid | 5.0253 | 100.5 | ||||||
Bottom | 5.0321 | 100.6 | ||||||
G3 | 15.0 | Top | 15.0679 | 15.0358 | 100.5 | 100.2 | 0.2517 | 0.2 |
Mid | 15.0057 | 100.0 | ||||||
Bottom | 15.0338 | 100.2 | ||||||
G4 | 30.0 | Top | 30.5151 | 30.8564 | 101.7 | 102.8 | 2.3180 | 2.8 |
Mid | 30.3908 | 101.3 | ||||||
Bottom | 31.6634 | 105.5 | ||||||
G5 & G7 | 70.0 | Top | 68.5567 | 68.8393 | 97.9 | 98.3 | 0.5132 | -1.7 |
Mid | 68.7349 | 98.2 | ||||||
Bottom | 69.2264 | 98.9 |
Applicant's summary and conclusion
- Conclusions:
- Oral administration of Genamin 3920 [2,2’-(Octylimino)bisethanol] for 90 consecutive days followed by 28 days of recovery period was found to be well tolerated in Wistar rats up to 350 mg/kg b.w./day without any obvious signs of toxicity.
On the basis of the study findings, the No Observed Adverse Effect Level (NOAEL) of Genamin 3920 [2,2’-(Octylimino)bisethanol] following 90-day repeated dose Oral administration in Wistar rats was 350 mg/kg b.w./day under the tested conditions. - Executive summary:
The aim of this study was to assess the possible health hazards which could arise from repeated exposure of Genamin 3920 via oral administration to rats over a period of 90 days.
The test item was administered daily in graduated doses to 4 groups of test animals, one dose level per group for a treatment period of 90 days. Animals of an additional control group were handled identically as the dose groups but received vehicle alone. The 5 groups comprised of 10 male and 10 female Wistar rats. To detect possible/ delayed occurrence or persistence of, or recovery from toxic effects, animals in the control and high dose recovery groups were observed for a period of 28 days
The vehicle and test item formulations were subjected to active ingredient analyses prior to treatment, during the 6th week and 13th week of the treatment period. The concentrations of Genamin 3920 [2,2’-(Octylimino)bisethanol] at all tested concentrations were within 100±10% of nominal concentrations, thereby meeting the acceptance criteria. The test item in formulation was found to be stable up to 48 hours.
Assessment of toxicity was based on mortality, clinical signs, body weights, feed consumption, neurobehavioral observations, clinical and anatomic pathology.
Body weight and food consumption were measured weekly.
At the conclusion of the treatment period, all animals were sacrificed and subjected to necropsy. The wet weight of organs of all animals were taken and preserved for histopathological observations.
A full histopathological evaluation of the tissues was performed on high dose and control animals. These examinations were extended to animals of all other dosage groups for treatment-related changes that were observed in the high dose group. Only organs and tissues of the other dosage groups showing changes in the high dose group were examined.
These examinations were also extended to animals subjected to necropsy at the end of the recovery period.
The following doses were evaluated:
Control: 0 mg/kg body weight
Low Dose: 25 mg/kg body weight
Medium Dose: 75 mg/kg body weight
Medium High Dose: 150 mg/kg body weight
High Dose: 350 mg/kg body weight
The test item formulation was prepared on basis of stability data (48h).
Summary Results:
Weekly body weight and feed consumption did not reveal treatment related changes and were comparable to concurrent vehicle controls.
No treatment related changes were observed in any of the haematology, clinical chemistry, coagulation and urinalysis parameters in test item treated groups including recovery groups as compared with respective vehicle controls.
No treatment related organ weight changes were observed in any of the organ in test item treated groups including recovery groups as compared with respective vehicle controls.
No test item related changes were observed in sperm motility and morphology of main and recovery groups as compared with respective vehicle controls.
On histopathological examination, one male sacrificed terminally from 350 mg/kg dose group showed multifocal necrosis in kidneys together with squamous cell hyperplasia in non-glandular stomach. In addition, two males from the same group showed mononuclear cell infiltration in non-glandular stomach. As the kidneys findings were limited to one animal from high dose group, it was considered as incidental not related to test item. However, histopathology findings observed in stomach were considered as test item related non-adverse finding due to the irritating properties of the test item. Moreover, no histopathological changes were observed in stomach and kidneys of recovery high dose group animals.
Conclusion:
On the basis of this 90-Day Repeated Dose Oral Toxicity study with Genamin 3920 in male and female Wistar rats with dose levels of 25, 75, 150, and 350 mg/kg bw/d, the following conclusions can be made:
Histopathological lesions (in stomach) which were attributable to treatment with the test item were considered to be the results of local irritant effects due to the physicochemical character of the test item.
No signs of systemic toxicity of Genamin 3920 were found at dose levels of 25, 75, 150 and 350 mg/kg/d. Thus, the NOAEL is assumed to be 350 mg/kg/d in both genders.
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