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EC number: 216-223-3 | CAS number: 1530-32-1
- 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
Endpoint summary
Administrative data
Description of key information
Repeated Dose Toxicity (Oral):
Based on all the available data, it was concluded that after repeated exposures of the test chemical via oral route, it caused adverse effects on hepatobiliary system. Therefore, the NOAEL and LOAEL for the test chemical was 60 and 120 mg/kg bw/day, respectively after 28 days of exposure.
Repeated Dose Toxicity (Inhalation):
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the test chemical which is reported as 6.600541739463232e-8 mmHg at 25 degree C. Also, considering the particle size distribution of the substance the majority of the particles was found to be in the range size of 150 micron to 106 micron which is much larger size range compared to the inhalable particulate matter .Thus, exposure to inhalable dust, mist and vapour of the test chemical is highly unlikely. Therefore this study is considered for waiver.
Repeated Dose Toxicity (Dermal):
The acute toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that the test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that the test chemical shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Data is from a study report.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- According to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house bred animals
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-7 Weeks
- Weight at study initiation: Male: 148.4g -153.8 g
Female: 147.1 g -158.6 g
- Fasting period before study: No Data Available
- Housing: Animals were housed in an autoclaved polycarbonate cages with stainless steel top grill having facilities for holding pellet feed and drinking water in polycarbonate bottle. Autoclaved corn cob was used as bedding material and it was changed at least once in a week.
- Diet (e.g. ad libitum): Rodent feed from a certified vendor was provided as ad libitum.
- Water (e.g. ad libitum): Aquaguard purified water was provided ad libitum by a water dispensing bottle.
- Acclimation period: Nineteen days under laboratory conditions, after veterinary examination. Only animals without any visible signs of illness were used for the study.
DETAILS OF FOOD AND WATER QUALITY: No Data Available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1°C – 23.4°C.
- Humidity (%): 51 – 61 %
- Air changes (per hr): 10 Air Changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle per day
IN-LIFE DATES:
From: 30-06-2020
To: 10-09-2020 - Route of administration:
- oral: gavage
- Details on route of administration:
- Administration of the test chemical by gavage is a common and accepted route of exposure for this type of studies.
- Vehicle:
- water
- Remarks:
- Distilled water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test chemical was weighed and transferred to a labelled beaker. 10 mL of distilled water was added and mixed with a glass rod. Final volume was made up to 50 ml to get a concentration of 3 mg/ml for Low Dose, 6 mg/ml for Intermediate dose and 12 mg/ml for High dose by mixing with magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
DIET PREPARATION
- Rate of preparation of diet (frequency): No Data Available
- Mixing appropriate amounts with (Type of food): No Data Available
- Storage temperature of food: No Data Available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water was used as a vehicle.
- Concentration in vehicle: 10 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw
- Lot/batch no. (if required): No Data Available
- Purity: No Data Available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability of dose formulation was checked before treatment start day at 0 and 6 hours. The test chemical was checked for its stability in the dose formulation with samples collected immediately (0 hours) and 6 hours post dose formulation preparation. Samples of the dose formulations were taken immediately after dilution of the concentrates with the diluents (vehicle) on treatment start date and treatment end date for homogeneity (mean of homogeneity was given as dose concentration) analyses. On week 3, samples of all dose formulations were taken for dose concentration analysis.Analysis was performed based on the validated analytical method.
Linearity: Linearity was carried out by injecting a minimum of 5 different test concentrations (three replications from each concentration).The correlation coefficient and regression was calculated (r=1.00).
Accuracy: Accuracy was performed at three levels ie., 50, 100, 150%. The mean recovery values of samples for 50% level is 99.82% , for 100% level is 99.58% and for 150% level is 98.99%.
Precision: The relative standard deviation of analysis of five independent fortifications samples were not exceed ±20% of the mean value.
Specificity: No interference was observed above 30 % of total peak area for target analyte. - Duration of treatment / exposure:
- 28 days for main group and 14 days of recoery period.
- Frequency of treatment:
- Once Daily
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control Group
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Remarks:
- Low Dose Group
- Dose / conc.:
- 60 mg/kg bw/day (actual dose received)
- Remarks:
- Mid Dose Group
- Dose / conc.:
- 120 mg/kg bw/day (actual dose received)
- Remarks:
- High Dose Group
- No. of animals per sex per dose:
- 5 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The doses for the main study were selected on the basis of a dose range finding (DRF) study. The doses for the DRF study were 0, 50, 100 and 200 mg/kg bw/day. During the treatment 03 Males and 04 Females showed Mortality in High dose (200 mg/kg Body weight). There was no mortality in Control, Low Dose and Mid Dose. Piloerection and dullness were observed in High dose group. Hence, based on the Dose Range Finding Study, the doses of 30, 60 and 120 mg/kg body weight were confirmed for main study.
- Rationale for animal assignment (if not random): Animals were selected and grouped based on stratified randomization by using body weights taken before start of treatment. Computerized statistical analysis was used for randomization (MS Excel programme).
- Fasting period before blood sampling for clinical biochemistry: The animals were placed individually in metabolic cages and fasted overnight before blood sampling but allowed access to water ad libitum.
- Rationale for selecting satellite groups: The satellite groups were selected to observe the reversibility of the effects that are observed during and after the dosing of the animals for 28 days.
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): No Data Available
- Other: No Data Available - Positive control:
- No Data Available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals was observed twice daily for morbidity and mortality while for Clinical Signs, Once daily during acclimatization phase and twice daily on first 3 days of treatment; once daily thereafter. During Recovery period, animals were observed once daily.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once before the first exposure and weekly after.
BODY WEIGHT: Yes
- Time schedule for examinations: Once during Acclimatization and before randomization and Weekly Once during Treatment Period and Recovery Period.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, Once weekly during treatment and recovery period.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
FOOD EFFICIENCY: No Data Available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations:
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Once during acclimatization, during week 4 in all animals of groups 1 and 4.
- Dose groups that were examined: All animals from all the dose groups were examined.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 29 (Main Groups) and Day 43 (Recovery Group), before sacrifice
- Anaesthetic used for blood collection: Yes (Isoflurane anesthesia)
- Animals fasted: Yes
- How many animals: All animals from all the dose groups.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 29 (Main Groups) and Day 43 (Recovery Group), before sacrifice
- Animals fasted: Yes
- How many animals: All animals from all the dose groups.
URINALYSIS: Yes
- Time schedule for collection of urine: Urine samples were collected in the morning before the blood collection.
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: End of week 4 for main groups and by the end of Week 6 for recovery groups.
- Dose groups that were examined: All animals from all the dose groups.
- Battery of functions tested: sensory activity / grip strength / motor activity
IMMUNOLOGY: Not specified
- Time schedule for examinations: No Data Available
- How many animals: No Data Available
- Dose groups that were examined: No Data Available
OTHER: No Data Available - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 1)
HISTOPATHOLOGY: Yes, All organ and tissue samples, as defined under Necropsy were processed, embedded and cut at an approximate thickness of 3 to 5 micrometers, stained with hematoxylin and eosin and examined under light microscope. Full histopathology was performed on the preserved organs and tissues of all animals in the control and high dose groups. Histopathology examination was extended to the organs such as liver, testes and epididymides in low dose and intermediate dose group. - Other examinations:
- No Data Available
- Statistics:
- The following statistical methods were used to analyze the body weight, feed consumption, organ weights as well as clinical pathology data.
• Data was summarized in tabular form. Statistical analysis was performed using SAS/STAT® Software (Version 9.3).
• All the data were analysed for homogeneity using Levene’s test
• The difference between the means was analyzed using Dunnet’s t- test
• Significant differences between control and treated groups analyzed using one-way ANOVA statistics
• Values were summarized as mean ± standard deviation (SD) - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs were observed in all the dose groups examined including the recovery groups.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality was observed in all the dose groups examined including the recovery groups.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No adverse effect on body weight was observed for treated groups when compared with control group. No significant and toxicological relevant changes in th body weight between treated and control group were observed.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No signficance in the feed consumption was observed in any of the treated and recovery groups when compared with vehicle control group.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No effects were observed after opthalmological examinations in both the control groups and treatment groups.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment related effects were observed in the both male and female animals with respect to hematological parameters viz RBC,WBC Hb, MCV, MCHC, PCV, PT and APTT when compared with control group. However, in the treatment group, Platelets count was increased in Low Dose (G2), Intermediate Dose (G3) and high dose (G4) group male rats when compared with control group was observed and in high dose recovery group females Monocytes count was decresed comparable with control. This signficance may not be attributed to treatment since all the haematological values fall with in the normal biological range and no biological significance was noted.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- There was no dose related effect on few biochemical parameters. There was a significant decrese in both Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in males. Significant changes were observed indicating the test chemical's effect on liver. In males, Urea levels, Bilirubin levels decreased, while Potassium levels increased in low dose group. In Mid Dose Group, Bilirubin levels decreased, while alkaline phosphatase levels and Potassium levels increased, when compared with the control group. In females, Glucose and Sodium levels increased in High dose group, while cholesterol and triglyceride levels decreased, when compared with control group.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No significant changes were observed in any of the treated groups and recovery group.
- Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No test chemical related effects on the grip strength, motor activity, sensory activity was noted in both treated and recovery group animals.
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Both in males and females organ weights of Heart increased High dose group (G4) compared with control group. In Recovery group Females, organ weights of Brain decreased High dose group (G4), when compared with control group.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- During necropsy, macroscopic lesions were observed on liver and lungs where hemorrhagic spots were observed in both the organs in high dose group. Apart from these observations, no other treatment related macroscopic finding in any of the animals in all groups including Systemic and Reproductive organs.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- In microscopic observations, sinusoidal hemorrhages were observed in liver in control males, but such effect was observed in both the sexes in high dose group. Also, Foci of necrosis/inflammation of hepatocytes were observed in centri lobular of liver in three male and two female animals from G4 group. Alveolar wall thickening or alveolar inflammation noticed in the lungs of two male and two female animals from G4 group.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- No clinical signs were observed in all the dose groups examined including the recovery groups. No mortality was observed in all the dose groups examined including the recovery groups. No adverse effect on body weight was observed for treated groups when compared with control group. No significant and toxicological relevant changes in the body weight between treated and control group were observed. No significance in the feed consumption was observed in any of the treated and recovery groups when compared with vehicle control group. No effects were observed after ophthalmological examinations in both the control groups and treatment groups. No treatment related effects were observed in the both male and female animals with respect to hematological parameters viz RBC, WBC, Hb, MCV, MCHC, PCV, PT and APTT when compared with control group. However, in the treatment group, Platelets count was increased in Low Dose (G2), Intermediate Dose (G3) and high dose (G4) group male rats when compared with control group was observed and in high dose recovery group females Monocytes count was decreased comparable with control. This significance may not be attributed to treatment since all the hematological values fall within the normal biological range and no biological significance was noted. There was no dose related effect on few biochemical parameters. There was a significant decrease in both Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in males. Significant changes were observed indicating the test chemical's effect on liver. In males, Urea levels, Bilirubin levels decreased, while Potassium levels increased in low dose group. In Mid Dose Group, Bilirubin levels decreased, while alkaline phosphatase levels and Potassium levels increased, when compared with the control group. In females, Glucose and Sodium levels increased in High dose group, while cholesterol and triglyceride levels decreased, when compared with control group. No significant changes were observed in any of the treated groups and recovery group. No test chemical related effects on the grip strength, motor activity, sensory activity was noted in both treated and recovery group animals. Both in males and females organ weights of Heart increased High dose group (G4) compared with control group. In Recovery group Females, organ weights of Brain decreased High dose group (G4), when compared with control group. During necropsy, macroscopic lesions were observed on liver and lungs where hemorrhagic spots were observed in both the organs in high dose group. Apart from these observations, no other treatment related macroscopic finding in any of the animals in all groups including Systemic and Reproductive organs. In microscopic observations, sinusoidal hemorrhages were observed in liver in control males, but such effect was observed in both the sexes in high dose group. Also, Foci of necrosis/inflammation of hepatocytes were observed in centri lobular of liver in three male and two female animals from G4 group. Alveolar wall thickening or alveolar inflammation noticed in the lungs of two male and two female animals from G4 group.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 60 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Dose descriptor:
- LOAEL
- Effect level:
- 120 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- gross pathology
- histopathology: non-neoplastic
- Remarks on result:
- other: Adverse effects were observed in liver and lungs.
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 120 mg/kg bw/day (actual dose received)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- no
- Conclusions:
- Based on all the available data, it was concluded that after repeated exposures of the test chemical via oral route, it caused adverse effects on hepatobiliary system. Therefore, the NOAEL and LOAEL for the test chemical was 60 and 120 mg/kg bw/day, respectively after 28 days of exposure.
- Executive summary:
A study according to the OECD Test Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents), performed using male and female Wistar Rats. The test chemical was administered via oral: gavage route. 5 animals per sex dose were used in the study. 6 groups were used in the study. The test chemical was administered in a dose range of 0, 30, 60 and 120 mg/kg bw/day as a control group, low dose, mid dose and high dose groups, respectively. Two recovery groups (0 mg/kg bw/day-Control Recovery and 1000 mg/kg bw/day-High Dose Recovery Group) were used in the study to observe the reversibility of the effects that would be observed in the main groups, if caused due to the test chemical. Distilled water was used as a vehicle. The test chemical was administered to the animals, once daily. The animals were dosed for 28 days, consecutively. The doses were selected on the basis of a Dose Range Finding (DRF) Study. In this study, the doses for the DRF study were 0, 50, 100 and 200 mg/kg bw/day. During the treatment 03 Males and 04 Females showed Mortality in High dose (200 mg/kg Body weight). There was no mortality in Control, Low Dose and Mid Dose. Piloerection and dullness were observed in High dose group. Hence, based on the Dose Range Finding Study, the doses of 30, 60 and 120 mg/kg body weight were confirmed for main study. As per the requirement according to OECD test guideline 407, animals was observed twice daily for morbidity and mortality while for Clinical Signs, Once daily during acclimatization phase and twice daily on first 3 days of treatment; once daily thereafter. During Recovery period, animals were observed once daily. Detailed clinical observations were done, once before the first exposure and weekly after. Body weights were examined once during Acclimatization and before randomization and Weekly Once during Treatment Period and Recovery Period. Also, feed consumption was observed Once weekly during treatment and recovery period. Opthalmoscopic examinations was performed once during acclimatization, during week 4 in all animals of groups 1 and 4. Blood samples for hematology and clinical biochemistry was collected from all animals under Isoflurane anesthesia system. The animals were placed individually in metabolic cages and fasted overnight before blood and urine sampling but allowed access to water ad libitum. Urine samples were collected in the morning before the blood collection. Blood samples were collected in the morning to reduce biological variation caused by circadian rhythms. Blood samples were drawn from the retro-orbital plexus using a micro-hematocrit heparinized glass capillary tube. Blood samples were centrifuged and plasma was separated for clinical biochemistry analysis. Examinations for functional observational battery was performed by end of week 4 for main groups and by the end of week 6 for recovery groups. Necropsy and histopathology was done on day 29 and day 43 for main group and recovery group animals, respectively. It was observed that, No clinical signs were observed in all the dose groups examined including the recovery groups. No mortality was observed in all the dose groups examined including the recovery groups. No adverse effect on body weight was observed for treated groups when compared with control group. No significant and toxicological relevant changes in the body weight between treated and control group were observed. No significance in the feed consumption was observed in any of the treated and recovery groups when compared with vehicle control group. No effects were observed after ophthalmological examinations in both the control groups and treatment groups. No treatment related effects were observed in the both male and female animals with respect to hematological parameters viz RBC, WBC Hb, MCV, MCHC, PCV, PT and APTT when compared with control group. However, in the treatment group, Platelets count was increased in Low Dose (G2), Intermediate Dose (G3) and high dose (G4) group male rats when compared with control group was observed and in high dose recovery group females Monocytes count was decreased comparable with control. This significance may not be attributed to treatment since all the hematological values fall within the normal biological range and no biological significance was noted. There was no dose related effect on few biochemical parameters. There was a significant decrease in both Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in males. Significant changes were observed indicating the test chemical's effect on liver. In males, Urea levels, Bilirubin levels decreased, while Potassium levels increased in low dose group. In Mid Dose Group, Bilirubin levels decreased, while alkaline phosphatase levels and Potassium levels increased, when compared with the control group. In females, Glucose and Sodium levels increased in High dose group, while cholesterol and triglyceride levels decreased, when compared with control group. No significant changes were observed in any of the treated groups and recovery group. No test chemical related effects on the grip strength, motor activity, sensory activity was noted in both treated and recovery group animals. Both in males and females when organ weights of Heart increased High dose group (G4) compared with control group. In Recovery group Females, organ weights of Brain decreased High dose group (G4), when compared with control group. During necropsy, macroscopic lesions were observed on liver and lungs where hemorrhagic spots were observed in both the organs in high dose group. Apart from these observations, no other treatment related macroscopic finding in any of the animals in all groups including Systemic and Reproductive organs. In microscopic observations, sinusoidal hemorrhages were observed in liver in control males, but such effect was observed in both the sexes in high dose group. Also, Foci of necrosis/inflammation of hepatocytes were observed in centri lobular of liver in three male and two female animals from G4 group. Alveolar wall thickening or alveolar inflammation noticed in the lungs of two male and two female animals from G4 group. Thus, based on all the available data, it was concluded that after repeated exposures of the test chemical via oral route, it caused adverse effects on hepatobiliary system. Therefore, the NOAEL and LOAEL for the test chemical was 60 and 120 mg/kg bw/day, respectively after 28 days of exposure.
- Endpoint:
- sub-chronic toxicity: oral
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- a sub-chronic toxicity study (90 days) does not need to be conducted because a reliable short-term toxicity study (28 days) is available showing severe toxicity effects according to the relevant criteria for classifying the substance, for which the observed NOAEL-28 days, with the application of an appropriate uncertainty factor, allows the extrapolation towards the NOAEL-90 days for the same route of exposure
Referenceopen allclose all
Table for Clinical Signs
TREATMENT
Day of observation | Control (G1) | Low dose (G2) | Middle dose (G3) | High dose (G4) | ||||
M | F | M | F | M | F | M | F | |
1 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
2 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
3 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
4 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
6 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
7 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
8 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
9 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
10 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
11 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
12 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
13 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
14 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
15 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
16 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
17 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
18 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
19 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
20 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
21 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
22 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
23 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
24 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
25 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
26 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
27 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
28 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 | 01/5 |
Key: M – Male; F – Female; Observation/No. of animals; 01 – Normal.
Recovery (R)
Day of observation | Control Recovery (G1R) | High dose Recovery (G4R) | ||
M | F | M | F | |
1 | 01/5 | 01/5 | 01/5 | 01/5 |
2 | 01/5 | 01/5 | 01/5 | 01/5 |
3 | 01/5 | 01/5 | 01/5 | 01/5 |
4 | 01/5 | 01/5 | 01/5 | 01/5 |
5 | 01/5 | 01/5 | 01/5 | 01/5 |
6 | 01/5 | 01/5 | 01/5 | 01/5 |
7 | 01/5 | 01/5 | 01/5 | 01/5 |
8 | 01/5 | 01/5 | 01/5 | 01/5 |
9 | 01/5 | 01/5 | 01/5 | 01/5 |
10 | 01/5 | 01/5 | 01/5 | 01/5 |
11 | 01/5 | 01/5 | 01/5 | 01/5 |
12 | 01/5 | 01/5 | 01/5 | 01/5 |
13 | 01/5 | 01/5 | 01/5 | 01/5 |
14 | 01/5 | 01/5 | 01/5 | 01/5 |
15 | 01/5 | 01/5 | 01/5 | 01/5 |
16 | 01/5 | 01/5 | 01/5 | 01/5 |
17 | 01/5 | 01/5 | 01/5 | 01/5 |
18 | 01/5 | 01/5 | 01/5 | 01/5 |
19 | 01/5 | 01/5 | 01/5 | 01/5 |
20 | 01/5 | 01/5 | 01/5 | 01/5 |
21 | 01/5 | 01/5 | 01/5 | 01/5 |
22 | 01/5 | 01/5 | 01/5 | 01/5 |
23 | 01/5 | 01/5 | 01/5 | 01/5 |
24 | 01/5 | 01/5 | 01/5 | 01/5 |
25 | 01/5 | 01/5 | 01/5 | 01/5 |
26 | 01/5 | 01/5 | 01/5 | 01/5 |
27 | 01/5 | 01/5 | 01/5 | 01/5 |
28 | 01/5 | 01/5 | 01/5 | 01/5 |
Recovery (R) Contd.
Day of observation | Control Recovery (G1R) | High dose Recovery (G4R) | ||
M | F | M | F | |
29 | 01/5 | 01/5 | 01/5 | 01/5 |
30 | 01/5 | 01/5 | 01/5 | 01/5 |
31 | 01/5 | 01/5 | 01/5 | 01/5 |
32 | 01/5 | 01/5 | 01/5 | 01/5 |
33 | 01/5 | 01/5 | 01/5 | 01/5 |
34 | 01/5 | 01/5 | 01/5 | 01/5 |
35 | 01/5 | 01/5 | 01/5 | 01/5 |
36 | 01/5 | 01/5 | 01/5 | 01/5 |
37 | 01/5 | 01/5 | 01/5 | 01/5 |
38 | 01/5 | 01/5 | 01/5 | 01/5 |
39 | 01/5 | 01/5 | 01/5 | 01/5 |
40 | 01/5 | 01/5 | 01/5 | 01/5 |
41 | 01/5 | 01/5 | 01/5 | 01/5 |
42 | 01/5 | 01/5 | 01/5 | 01/5 |
Key: M – Male; F – Female; Observation/No. of animals; 01 – Normal.
Table for Mortality
TREATMENT
Days of observation | G1 | G2 | G3 | G4 | ||||
M | F | M | F | M | F | M | F | |
1 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
2 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
3 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
4 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
6 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
7 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
8 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
9 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
10 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
11 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
12 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
13 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
14 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
15 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
16 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
17 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
18 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
19 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
20 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
21 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
22 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
23 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
24 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
25 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
26 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
27 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
28 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 |
Key: M – Male; F – Female; No. of animals found dead/Total no. of animals.
Recovery (R)
Days of observation | G1R | G4R | ||
M | F | M | F | |
29 | 0/5 | 0/5 | 0/5 | 0/5 |
30 | 0/5 | 0/5 | 0/5 | 0/5 |
31 | 0/5 | 0/5 | 0/5 | 0/5 |
32 | 0/5 | 0/5 | 0/5 | 0/5 |
33 | 0/5 | 0/5 | 0/5 | 0/5 |
34 | 0/5 | 0/5 | 0/5 | 0/5 |
35 | 0/5 | 0/5 | 0/5 | 0/5 |
36 | 0/5 | 0/5 | 0/5 | 0/5 |
37 | 0/5 | 0/5 | 0/5 | 0/5 |
38 | 0/5 | 0/5 | 0/5 | 0/5 |
39 | 0/5 | 0/5 | 0/5 | 0/5 |
40 | 0/5 | 0/5 | 0/5 | 0/5 |
41 | 0/5 | 0/5 | 0/5 | 0/5 |
42 | 0/5 | 0/5 | 0/5 | 0/5 |
Key: M – Male; F – Female; No. of animals found dead/Total no. of animals.
Table for Body Weights (G) (Males)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 151.8 | 151.3 | 151.5 | 151.6 |
SD | 2.05 | 1.55 | 1.67 | 1.76 | |
Min | 148.4 | 149.3 | 149.2 | 149.3 | |
Max | 153.8 | 153.2 | 153.2 | 153.8 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 166.1 | 163.9 | 164.8 | 164.9 |
SD | 1.85 | 1.88 | 1.87 | 1.43 | |
Min | 163.7 | 161.2 | 162.4 | 163.2 | |
Max | 168.7 | 166.4 | 166.8 | 166.8 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 177.8 | 178.1 | 178.6 | 179.4 |
SD | 1.69 | 1.90 | 0.80 | 1.00 | |
Min | 175.8 | 175.4 | 177.4 | 178.1 | |
Max | 179.8 | 180.3 | 179.4 | 180.7 | |
N | 5 | 5 | 5 | 5 |
Day 22 | Mean | 190.3 | 192.9 | 192.4 | 193.8 |
SD | 1.95 | 2.19 | 1.16 | 0.65 | |
Min | 187.4 | 190.2 | 191.2 | 193.1 | |
Max | 192.5 | 195.5 | 193.7 | 194.7 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 203.2 | 208.1 | 207.5 | 207.7 |
SD | 1.98 | 2.20 | 1.26 | 0.82 | |
Min | 200.4 | 205.4 | 206.3 | 206.9 | |
Max | 205.5 | 210.3 | 209.2 | 208.7 | |
N | 5 | 5 | 5 | 5 |
Table for Body Weights (G) (Females)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 151.5 | 151.4 | 151.7 | 151.6 |
SD | 2.87 | 3.18 | 3.40 | 4.05 | |
Min | 147.9 | 147.1 | 148.4 | 148.5 | |
Max | 155.7 | 155.4 | 156.9 | 158.6 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 164.4 | 164.2 | 164.2 | 165.1 |
SD | 2.97 | 2.29 | 2.29 | 3.80 | |
Min | 160.3 | 161.7 | 161.7 | 161.2 | |
Max | 168.3 | 167.3 | 167.3 | 171.3 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 176.3 | 178.2 | 180.3 | 180.2 |
SD | 3.11 | 2.01 | 3.46 | 3.82 | |
Min | 172.9 | 175.2 | 177.2 | 176.5 | |
Max | 180.5 | 180.5 | 185.3 | 186.5 | |
N | 5 | 5 | 5 | 5 |
Day 22 | Mean | 192.7 | 193.6 | 194.6 | 194.5 |
SD | 1.60 | 1.75 | 4.15 | 4.37 | |
Min | 190.9 | 191.4 | 191.2 | 190.3 | |
Max | 194.8 | 195.9 | 200.3 | 201.6 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 206.8 | 208.4 | 209.7 | 208.6 |
SD | 2.05 | 1.87 | 3.13 | 4.25 | |
Min | 204.1 | 206.2 | 207.1 | 204.3 | |
Max | 208.9 | 211.1 | 214.5 | 215.3 | |
N | 5 | 5 | 5 | 5 |
Table for Body Weights (G) (Males)
RECOVERY
| Group 1R | Group 4R | |
Day 1 | Mean | 151.2 | 151.6 |
SD | 1.42 | 1.65 | |
Min | 149.2 | 149.2 | |
Max | 152.5 | 153.7 | |
N | 5 | 5 | |
Day 8 | Mean | 164.9 | 164.7 |
SD | 1.19 | 1.79 | |
Min | 163.2 | 163.2 | |
Max | 166.3 | 167.4 | |
N | 5 | 5 | |
Day 15 | Mean | 179.3 | 180.2 |
SD | 1.49 | 2.12 | |
Min | 177.5 | 178.1 | |
Max | 181.4 | 183.3 | |
N | 5 | 5 |
Day 22 | Mean | 193.5 | 193.6 |
SD | 1.75 | 2.04 | |
Min | 191.3 | 191.4 | |
Max | 195.6 | 196.2 | |
N | 5 | 5 | |
Day 29 | Mean | 207.5 | 207.9 |
SD | 1.71 | 1.94 | |
Min | 205.5 | 205.2 | |
Max | 209.9 | 210.3 | |
N | 5 | 5 | |
Day 36 | Mean | 221.5 | 222.1 |
SD | 1.70 | 2.65 | |
Min | 219.3 | 219.3 | |
Max | 223.4 | 225.5 | |
N | 5 | 5 | |
Day 42 | Mean | 235.6 | 235.6 |
SD | 1.73 | 2.48 | |
Min | 233.1 | 232.6 | |
Max | 237.5 | 239.3 | |
N | 5 | 5 |
Table for Body Weights (G) (Females)
RECOVERY
| Group 1R | Group 4R | |
Day 1 | Mean | 151.6 | 151.3 |
SD | 1.78 | 2.54 | |
Min | 149.6 | 149.5 | |
Max | 154.2 | 155.4 | |
N | 5 | 5 | |
Day 8 | Mean | 164.4 | 165.2 |
SD | 1.87 | 3.02 | |
Min | 162.3 | 162.6 | |
Max | 167.1 | 169.7 | |
N | 5 | 5 | |
Day 15 | Mean | 178.8 | 179.5 |
SD | 2.07 | 3.18 | |
Min | 176.2 | 176.2 | |
Max | 181.9 | 184.3 | |
N | 5 | 5 |
| Group 1R | Group 4R | |
Day 22 | Mean | 194.1 | 193.7 |
SD | 1.60 | 3.35 | |
Min | 192.7 | 191.2 | |
Max | 196.7 | 199.3 | |
N | 5 | 5 | |
Day 29 | Mean | 208.8 | 207.5 |
SD | 1.85 | 3.58 | |
Min | 207.3 | 204.3 | |
Max | 211.8 | 213.4 | |
N | 5 | 5 | |
Day 36 | Mean | 223.7 | 222.2 |
SD | 1.46 | 3.84 | |
Min | 221.9 | 218.6 | |
Max | 225.6 | 228.2 | |
N | 5 | 5 | |
Day 42 | Mean | 236.5 | 235.9 |
SD | 1.97 | 4.89 | |
Min | 234.1 | 231.2 | |
Max | 238.6 | 243.2 | |
N | 5 | 5 |
BODY WEIGHT GAIN (%) (MALES)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 0.0 | 0.0 | 0.0 | 0.0 |
SD | 0.00 | 0.00 | 0.00 | 0.00 | |
Min | 0.0 | 0.0 | 0.0 | 0.0 | |
Max | 0.0 | 0.0 | 0.0 | 0.0 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 9.4 | 8.4 | 8.8 | 8.8 |
SD | 0.58 | 1.78 | 0.45 | 1.10 | |
Min | 8.9 | 5.2 | 8.2 | 6.8 | |
Max | 10.3 | 9.6 | 9.2 | 9.4 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 17.1 | 17.7 | 17.9 | 18.4 |
SD | 0.97 | 1.81 | 0.91 | 1.29 | |
Min | 15.8 | 14.5 | 16.8 | 16.3 | |
Max | 18.5 | 18.8 | 18.9 | 19.5 | |
N | 5 | 5 | 5 | 5 |
Day 22 | Mean | 25.3 | 27.5 | 27.1 | 27.9 |
SD | 1.08 | 1.88 | 1.28 | 1.48 | |
Min | 23.6 | 24.2 | 25.2 | 25.8 | |
Max | 26.3 | 28.6 | 28.2 | 29.5 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 33.9 | 37.5 | 37.0 | 37.1 |
SD | 1.02 | 1.95 | 1.30 | 1.59 | |
Min | 32.5 | 34.1 | 35.0 | 34.9 | |
Max | 35.0 | 38.8 | 38.3 | 38.7 | |
N | 5 | 5 | 5 | 5 |
BODY WEIGHT GAIN (%) (FEMALES)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 0.0 | 0.0 | 0.0 | 0.0 |
SD | 0.00 | 0.00 | 0.00 | 0.00 | |
Min | 0.0 | 0.0 | 0.0 | 0.0 | |
Max | 0.0 | 0.0 | 0.0 | 0.0 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 8.5 | 8.4 | 9.1 | 8.9 |
SD | 0.28 | 1.08 | 0.50 | 0.60 | |
Min | 8.1 | 7.7 | 8.4 | 8.0 | |
Max | 8.8 | 10.3 | 9.8 | 9.4 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 16.3 | 17.7 | 18.8 | 18.9 |
SD | 0.65 | 1.74 | 0.54 | 0.78 | |
Min | 15.6 | 16.2 | 18.1 | 17.6 | |
Max | 17.1 | 20.7 | 19.4 | 19.5 | |
N | 5 | 5 | 5 | 5 |
Day 22 | Mean | 27.2 | 27.9 | 28.3 | 28.3 |
SD | 2.28 | 1.86 | 0.78 | 1.00 | |
Min | 24.2 | 26.1 | 27.2 | 27.1 | |
Max | 29.3 | 31.0 | 29.0 | 29.4 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 36.5 | 37.7 | 38.2 | 37.6 |
SD | 2.51 | 1.95 | 1.23 | 1.29 | |
Min | 34.0 | 35.8 | 36.7 | 35.8 | |
Max | 39.1 | 40.9 | 39.6 | 38.9 | |
N | 5 | 5 | 5 | 5 |
BODY WEIGHT GAIN (%) (MALES)
RECOVERY
| Group 1R | Group 4R | |
Day 1 | Mean | 0.0 | 0.0 |
SD | 0.00 | 0.00 | |
Min | 0.0 | 0.0 | |
Max | 0.0 | 0.0 | |
N | 5 | 5 | |
Day 8 | Mean | 9.1 | 8.6 |
SD | 0.39 | 0.57 | |
Min | 8.5 | 7.9 | |
Max | 9.4 | 9.4 | |
N | 5 | 5 | |
Day 15 | Mean | 18.6 | 18.9 |
SD | 0.74 | 0.52 | |
Min | 17.8 | 18.1 | |
Max | 19.5 | 19.4 | |
N | 5 | 5 |
Day 22 | Mean | 28.0 | 27.7 |
SD | 0.46 | 0.85 | |
Min | 27.3 | 26.5 | |
Max | 28.5 | 28.8 | |
N | 5 | 5 | |
Day 29 | Mean | 37.3 | 37.1 |
SD | 0.75 | 1.19 | |
Min | 36.4 | 35.6 | |
Max | 38.1 | 38.9 | |
N | 5 | 5 | |
Day 36 | Mean | 46.5 | 46.5 |
SD | 0.89 | 1.35 | |
Min | 45.6 | 44.9 | |
Max | 47.7 | 48.3 | |
N | 5 | 5 | |
Day 42 | Mean | 55.9 | 55.4 |
SD | 0.90 | 1.43 | |
Min | 55.0 | 53.7 | |
Max | 57.2 | 57.6 | |
N | 5 | 5 |
BODY WEIGHT GAIN (%) (FEMALES)
RECOVERY
| Group 1R | Group 4R | |
Day 1 | Mean | 0.0 | 0.0 |
SD | 0.00 | 0.00 | |
Min | 0.0 | 0.0 | |
Max | 0.0 | 0.0 | |
N | 5 | 5 | |
Day 8 | Mean | 8.4 | 9.1 |
SD | 0.44 | 0.30 | |
Min | 7.8 | 8.8 | |
Max | 9.0 | 9.6 | |
N | 5 | 5 | |
Day 15 | Mean | 18.0 | 18.6 |
SD | 0.43 | 1.13 | |
Min | 17.3 | 17.9 | |
Max | 18.4 | 20.6 | |
N | 5 | 5 |
Day 22 | Mean | 28.0 | 28.0 |
SD | 0.63 | 0.47 | |
Min | 27.4 | 27.5 | |
Max | 28.8 | 28.6 | |
N | 5 | 5 | |
Day 29 | Mean | 37.7 | 37.1 |
SD | 0.76 | 0.65 | |
Min | 36.8 | 36.3 | |
Max | 38.6 | 38.0 | |
N | 5 | 5 | |
Day 36 | Mean | 47.6 | 46.8 |
SD | 1.47 | 0.66 | |
Min | 46.3 | 45.8 | |
Max | 50.1 | 47.7 | |
N | 5 | 5 | |
Day 42 | Mean | 56.0 | 55.9 |
SD | 2.24 | 0.98 | |
Min | 53.7 | 54.2 | |
Max | 59.4 | 56.7 | |
N | 5 | 5 |
FEED CONSUMPTION (G/ANIMAL/DAY) (MALES)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Week 1 | Mean | 16.25 | 16.47 | 16.49 | 16.30 |
SD | 2.76 | 2.98 | 2.63 | 2.73 | |
Week 2 | Mean | 16.25 | 16.47 | 16.49 | 16.30 |
SD | 2.76 | 2.98 | 2.63 | 2.73 | |
Week 3 | Mean | 16.25 | 16.47 | 16.49 | 16.30 |
SD | 2.76 | 2.98 | 2.63 | 2.73 | |
Week 4 | Mean | 16.25 | 16.47 | 16.49 | 16.30 |
SD | 2.76 | 2.98 | 2.63 | 2.73 |
FEED CONSUMPTION (G/ANIMAL/DAY) (MALES)
Recovery (R)
| Group 1R | Group 4R | |
Week 1 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 | |
Week 2 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 | |
Week 3 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 | |
Week 4 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 | |
Week 5 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 | |
Week 6 | Mean | 16.43 | 16.31 |
SD | 2.34 | 2.32 |
FEED CONSUMPTION (G/ANIMAL/DAY) (FEMALES)
TREATMENT
| Group 1 | Group 2 | Group 3 | Group 4 | |
Week 1 | Mean | 16.58 | 16.22 | 16.21 | 16.27 |
SD | 3.05 | 2.93 | 2.80 | 2.89 | |
Week 2 | Mean | 16.58 | 16.22 | 16.21 | 16.27 |
SD | 3.05 | 2.93 | 2.80 | 2.89 | |
Week 3 | Mean | 16.58 | 16.22 | 16.21 | 16.27 |
SD | 3.05 | 2.93 | 2.80 | 2.89 | |
Week 4 | Mean | 16.58 | 16.22 | 16.21 | 16.27 |
SD | 3.05 | 2.93 | 2.80 | 2.89 |
FEED CONSUMPTION (G/ANIMAL/DAY) (FEMALES)
RECOVERY (R)
| Group 1R | Group 4R | |
Week 1 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 | |
Week 2 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 | |
Week 3 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 | |
Week 4 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 | |
Week 5 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 | |
Week 6 | Mean | 16.25 | 16.30 |
SD | 2.76 | 2.57 |
DETAILED CLINICAL EXAMINATIONS
Group CONTROL(G1)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
Group Low Dose(G2)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
Group Intermediate Dose(G3)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
Group High Dose(G4)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
Group Vehicle Control Recovery(G1R)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 | Day 36 | Day 42 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
Group High Dose Recovery(G4R)
S.NO | Parameter | Pre Dose | Day 8 | Day 15 | Day 22 | Day 28 | Day 36 | Day 42 |
1 | Body Posture | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
2 | Gait | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
3 | Skin | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
4 | Fur | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
5 | Eyes | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
6 | Mucous membrane | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
7 | Respiratory pattern | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
8 | Salivation | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
9 | Response to handling | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
10 | Convulsions | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
11 | Stereotypic behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
12 | Bizzare Behaviour | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) | 1(10) |
Key: 1(10) – Observation(No of animals), 1-Normal
HEMATOLOGY – MALES
Week -04
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | |
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | ||
Group 1 | Mean | 9.21 | 16.28 | 52.30 | 57.54 | 17.98 | 31.26 | 1.87 |
SD | 2.493 | 3.269 | 11.744 | 4.510 | 1.692 | 0.750 | 0.111 | |
Group 2 | Mean | 8.75 | 15.46 | 49.30 | 56.66 | 17.78 | 31.36 | 1.87 |
SD | 0.759 | 0.456 | 1.754 | 4.697 | 1.632 | 0.462 | 0.041 | |
Group 3 | Mean | 8.46 | 14.10 | 45.54 | 54.40 | 16.88 | 30.98 | 1.85 |
SD | 1.134 | 0.875 | 3.035 | 6.120 | 2.202 | 0.701 | 0.069 | |
Group 4 | Mean | 8.19 | 14.74 | 46.80 | 57.30 | 18.04 | 31.50 | 1.84 |
SD | 0.624 | 0.503 | 1.726 | 2.664 | 0.783 | 0.374 | 0.045 |
| PLT | WBC | DC (%) | PT | APTT | |||||
X103cells/µl | X103cells/ µl | Neut | Lymph | Mono | Eos | Baso | Sec | Sec | ||
Group 1 | Mean | 622.80 | 17.54 | 20.60 | 74.60 | 3.20 | 1.60 | 0.00 | 16.20 | 42.20 |
SD | 97.983 | 3.211 | 13.428 | 14.346 | 0.447 | 0.894 | 0.000 | 1.095 | 2.950 | |
Group 2 | Mean | 911.60! | 18.44 | 10.20 | 86.00 | 2.40 | 1.40 | 0.00 | 16.40 | 44.20 |
SD | 154.936 | 5.244 | 2.168 | 2.345 | 0.548 | 0.548 | 0.000 | 1.140 | 2.950 | |
Group 3 | Mean | 930.40* | 23.54 | 13.20 | 82.00 | 3.00 | 1.80 | 0.00 | 17.60 | 43.20 |
SD | 95.340 | 7.606 | 3.271 | 3.674 | 0.707 | 0.447 | 0.000 | 1.140 | 3.421 | |
Group 4 | Mean | 947.40# | 25.76 | 12.40 | 83.00 | 2.80 | 1.80 | 0.00 | 17.40 | 41.40 |
SD | 126.211 | 6.158 | 3.647 | 3.674 | 0.447 | 0.447 | 0.000 | 1.140 | 3.209 |
! Significant at p ≥ 0.05 level with group 1, * Significant at p ≥ 0.05 level with group 1, # Significant at p ≥ 0.05 level with group 1.
HEMATOLOGY – MALES
Week -06
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | |
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | ||
Group 1R | Mean | 8.90 | 14.92 | 47.74 | 53.76 | 16.78 | 31.24 | 1.84 |
SD | 0.528 | 0.646 | 2.056 | 3.704 | 1.121 | 0.261 | 0.073 | |
Group 4R | Mean | 9.48 | 16.52 | 53.84 | 57.02 | 17.50 | 30.68 | 1.84 |
SD | 1.336 | 1.925 | 6.953 | 3.666 | 1.382 | 0.705 | 0.072 |
| PLT | WBC | DC (%) | PT | APTT | |||||
x103cells/µL | x103cells/ µL | Neut | Lymph | Mono | Eos | Baso | Sec | Sec | ||
Group 1R | Mean | 811.40 | 18.46 | 14.00 | 81.20 | 3.20 | 1.60 | 0.00 | 16.00 | 41.80 |
SD | 106.129 | 3.129 | 5.612 | 7.596 | 1.304 | 1.140 | 0.000 | 1.225 | 2.683 | |
Group 4R | Mean | 696.80 | 22.00 | 23.40 | 71.00 | 4.00 | 1.60 | 0.00 | 16.40 | 41.20 |
SD | 165.194 | 15.086 | 14.893 | 17.263 | 1.581 | 1.140 | 0.000 | 1.140 | 2.387 |
HEMATOLOGY – FEMALES
Week -04
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | |
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | ||
Group 1 | Mean | 7.71 | 14.16 | 43.32 | 56.60 | 18.54 | 32.72 | 1.85 |
SD | 0.985 | 0.792 | 2.729 | 4.243 | 1.598 | 0.370 | 0.080 | |
Group 2 | Mean | 8.11 | 13.86 | 42.74 | 52.66 | 17.08 | 32.42 | 1.86 |
SD | 0.656 | 1.307 | 3.960 | 1.352 | 0.676 | 0.653 | 0.076 | |
Group 3 | Mean | 8.26 | 14.44 | 45.32 | 55.08 | 17.58 | 31.90 | 1.89 |
SD | 0.780 | 0.336 | 1.932 | 3.241 | 1.438 | 0.682 | 0.046 | |
Group 4 | Mean | 7.44 | 14.92 | 44.22 | 59.94 | 20.18 | 33.66 | 1.86 |
SD | 0.802 | 0.814 | 2.758 | 4.620 | 1.760 | 0.994 | 0.068 |
| PLT | WBC | DC (%) | PT | APTT | |||||
X103cells/µl | X103cells/ µl | Neut | Lymph | Mono | Eos | Baso | Sec | Sec | ||
Group 1 | Mean | 787.60 | 21.58 | 11.20 | 84.00 | 3.40 | 1.40 | 0.00 | 16.40 | 40.80 |
SD | 186.871 | 4.871 | 2.280 | 2.236 | 0.894 | 0.548 | 0.000 | 1.140 | 1.789 | |
Group 2 | Mean | 921.60 | 22.86 | 13.80 | 81.80 | 2.60 | 1.80 | 0.00 | 15.60 | 42.20 |
SD | 29.246 | 7.730 | 3.421 | 3.768 | 0.548 | 0.447 | 0.000 | 1.140 | 2.168 | |
Group 3 | Mean | 933.80 | 19.36 | 15.20 | 79.60 | 3.60 | 1.60 | 0.00 | 16.60 | 42.80 |
SD | 111.237 | 5.647 | 5.891 | 7.503 | 0.894 | 0.894 | 0.000 | 1.342 | 2.864 | |
Group 4 | Mean | 962.80 | 16.34 | 10.40 | 85.40 | 3.00 | 1.20 | 0.00 | 16.60 | 40.40 |
SD | 119.242 | 5.671 | 2.608 | 2.510 | 0.000 | 0.447 | 0.000 | 1.673 | 2.881 |
HEMATOLOGY – FEMALES
Week -06
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocytes | |
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | ||
Group 1R | Mean | 8.31 | 14.48 | 44.52 | 53.62 | 17.44 | 32.56 | 1.90 |
SD | 0.350 | 0.460 | 1.711 | 0.887 | 0.344 | 0.329 | 0.091 | |
Group 4R | Mean | 7.90 | 13.12 | 43.60 | 55.50 | 16.74 | 30.06 | 1.89 |
SD | 0.868 | 1.796 | 3.055 | 4.435 | 2.745 | 3.479 | 0.044 |
| PLT | WBC | DC (%) | PT | APTT | |||||
x103cells/µL | x103cells/ µL | Neut | Lymph | Mono | Eos | Baso | Sec | Sec | ||
Group 1R | Mean | 866.40 | 14.92 | 12.80 | 81.80 | 3.60 | 1.80 | 0.00 | 15.60 | 43.60 |
SD | 93.055 | 3.104 | 3.768 | 3.347 | 0.894 | 0.447 | 0.000 | 1.140 | 3.435 | |
Group 4R | Mean | 758.80 | 17.36 | 13.00 | 83.60 | 2.40# | 1.00 | 0.00 | 16.40 | 41.80 |
SD | 266.210 | 6.579 | 1.581 | 2.302 | 0.548 | 0.707 | 0.000 | 1.140 | 3.347 |
#Significant at p ≤ 0.05 level with group 1
CLINICAL BIOCHEMISTRY – MALES
WEEK -04
| GLU | Urea | CREA | BLI | ALT | AST | ALP | TPO | |
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | ||
Group 1 | Mean | 99.00 | 54.20 | 0.90 | 0.13 | 73.80 | 168.80 | 232.00 | 7.04 |
SD | 16.90 | 16.18 | 0.34 | 0.02 | 45.16 | 48.40 | 52.53 | 0.33 | |
Group 2 | Mean | 100.40 | 29.20! | 0.72 | 0.09! | 65.80 | 151.60 | 272.80 | 7.26 |
SD | 18.34 | 5.54 | 0.04 | 0.01 | 10.08 | 8.56 | 69.55 | 0.24 | |
Group 3 | Mean | 73.60 | 41.60 | 0.70 | 0.10* | 59.60 | 167.40 | 377.20* | 7.48 |
SD | 15.95 | 5.18 | 0.07 | 0.01 | 8.96 | 26.94 | 88.09 | 0.47 | |
Group 4 | Mean | 92.20 | 42.00 | 0.74 | 0.12 | 59.60 | 146.80 | 289.80 | 7.42 |
SD | 21.72 | 3.81 | 0.05 | 0.02 | 6.07 | 23.45 | 105.77 | 0.24 |
! Significant at p ≤ 0.05 level with group 1, ! Significant at p ≤ 0.05 level with group 1, * Significant at p ≤ 0.05 level with group 1
* Significant at p ≥ 0.05 level with group 1.
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1 | Mean | 2.26 | 4.76 | 62.40 | 66.20 | 142.86 | 4.01 | 102.58 | 1.92 | 0.47 |
SD | 0.35 | 0.29 | 42.91 | 23.92 | 5.37 | 0.28 | 5.00 | 1.34 | 0.08 | |
Group 2 | Mean | 2.41 | 4.86 | 46.00 | 88.40 | 138.54 | 4.82! | 98.62 | 1.34 | 0.49 |
SD | 0.18 | 0.21 | 9.67 | 32.25 | 0.90 | 0.28 | 0.63 | 0.96 | 0.05 | |
Group 3 | Mean | 2.17 | 5.32 | 51.00 | 97.60 | 139.34 | 4.87* | 99.34 | 3.38 | 0.41 |
SD | 0.30 | 0.70 | 6.60 | 16.09 | 1.15 | 0.42 | 2.12 | 1.24 | 0.11 | |
Group 4 | Mean | 2.34 | 5.10 | 47.20 | 91.20 | 139.24 | 4.40 | 99.48 | 1.82 | 0.45 |
SD | 0.10 | 0.20 | 9.86 | 11.90 | 0.36 | 0.15 | 2.24 | 1.01 | 0.03 |
! Significant at p ≥ 0.05 level with group 1, * Significant at p ≥ 0.05 level with group 1.
CLINICAL BIOCHEMISTRY – MALES - RECOVERY
WEEK -06
| GLU | Urea | CREA | BLI | ALT | AST | ALP | TPO | |
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | ||
Group 1R | Mean | 91.60 | 45.20 | 0.74 | 0.10 | 60.00 | 161.80 | 363.60 | 7.76 |
SD | 23.44 | 5.40 | 0.05 | 0.03 | 4.00 | 27.87 | 98.28 | 0.57 | |
Group 4R | Mean | 92.80 | 41.00 | 1.32 | 0.12 | 75.80 | 165.40 | 281.20 | 8.52 |
SD | 15.91 | 7.04 | 0.86 | 0.07 | 36.48 | 37.27 | 193.31 | 1.76 |
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1R | Mean | 2.27 | 5.48 | 36.02 | 86.20 | 137.58 | 4.52 | 98.60 | 1.28 | 0.42 |
SD | 0.13 | 0.66 | 17.97 | 25.72 | 1.83 | 0.21 | 1.86 | 0.34 | 0.07 | |
Group 4R | Mean | 2.31 | 6.20 | 44.60 | 89.60 | 146.90 | 4.87 | 106.22 | 31.94 | 0.42 |
SD | 0.30 | 2.05 | 17.08 | 41.84 | 9.21 | 0.40 | 9.02 | 36.68 | 0.15 |
CLINICAL BIOCHEMISTRY – FEMALES
WEEK -04
| GLU | Urea | CREA | BLI | ALT | AST | ALP | TPO | |
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | ||
Group 1 | Mean | 89.80 | 40.40 | 0.70 | 0.09 | 59.80 | 141.80 | 246.40 | 21.68 |
SD | 14.08 | 4.77 | 0.00 | 0.05 | 15.88 | 11.95 | 60.95 | 32.04 | |
Group 2 | Mean | 86.20 | 30.80 | 0.78 | 0.10 | 61.80 | 159.40 | 287.60 | 7.78 |
SD | 8.41 | 7.82 | 0.04 | 0.01 | 12.28 | 8.96 | 71.00 | 0.72 | |
Group 3 | Mean | 75.00 | 47.40 | 0.78 | 0.09 | 53.40 | 137.80 | 305.60 | 7.70 |
SD | 11.22 | 7.54 | 0.08 | 0.02 | 12.12 | 28.50 | 134.46 | 0.57 | |
Group 4 | Mean | 60.40# | 39.40 | 0.72 | 0.12 | 55.20 | 151.00 | 204.00 | 7.54 |
SD | 8.17 | 5.50 | 0.04 | 0.05 | 6.38 | 15.36 | 71.40 | 0.47 |
# Significant at p ≤ 0.05 level with group 1
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1 | Mean | 2.37 | 5.06 | 58.40 | 122.60 | 137.94 | 4.33 | 98.62 | 1.98 | 0.46 |
SD | 0.12 | 0.28 | 8.56 | 49.27 | 0.90 | 0.43 | 2.27 | 1.51 | 0.03 | |
Group 2 | Mean | 2.16 | 5.64 | 44.40! | 49.00! | 137.86 | 4.74 | 100.54 | 2.54 | 0.38 |
SD | 0.27 | 0.75 | 5.73 | 6.52 | 0.66 | 0.19 | 0.99 | 0.65 | 0.08 | |
Group 3 | Mean | 2.31 | 4.70 | 56.60 | 92.80 | 139.06 | 4.71 | 100.24 | 14.36 | 0.43 |
SD | 0.28 | 1.91 | 11.33 | 28.97 | 0.64 | 0.31 | 1.45 | 27.42 | 0.10 | |
Group 4 | Mean | 2.45 | 5.08 | 54.80 | 80.40 | 138.32 | 4.45 | 99.46 | 1.34 | 0.48 |
SD | 0.15 | 0.51 | 6.22 | 28.14 | 0.87 | 0.41 | 1.74 | 0.86 | 0.06 |
! Significant at p ≤ 0.05 level with group 1, ! Significant at p ≤ 0.05 level with group 1
CLINICAL BIOCHEMISTRY – FEMALES - RECOVERY
WEEK -06
| GLU | Urea | CREA | BLI | ALT | AST | ALP | TPO | |
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | ||
Group 1R | Mean | 90.80 | 45.20 | 0.80 | 0.14 | 49.00 | 139.20 | 188.00 | 7.90 |
SD | 8.93 | 7.16 | 0.00 | 0.08 | 4.90 | 21.11 | 66.43 | 0.41 | |
Group 4R | Mean | 97.80 | 47.00 | 0.82 | 0.12 | 31.38 | 136.00 | 262.20 | 7.76 |
SD | 9.42 | 8.09 | 0.08 | 0.05 | 25.66 | 7.97 | 135.13 | 0.31 |
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1R | Mean | 2.31 | 6.20 | 44.60 | 89.60 | 146.90 | 4.87 | 106.22 | 31.94 | 0.42 |
SD | 0.30 | 2.05 | 17.08 | 41.84 | 9.21 | 0.40 | 9.02 | 36.68 | 0.15 | |
Group 4R | Mean | 2.51 | 5.26 | 53.80 | 117.60# | 139.98# | 4.24 | 100.50 | 9.58 | 0.46 |
SD | 0.08 | 0.34 | 8.58 | 23.28 | 1.08 | 0.42 | 0.74 | 17.32 | 0.03 |
#Significant at p ≥ 0.05 level with group 1, # Significant at p ≥ 0.05 level with group 1
URINANALYSIS – MALES
TREATMENT (Week 4)
| pH | SPECIFIC GRAVITY | VOLUME | |
(pH) | (SG) | mL | ||
Group 1 | Mean | 9.00 | 1.006 | 11.40 |
SD | 0.00 | 0.01 | 1.95 | |
Group 2 | Mean | 9.00 | 1.008 | 12.40 |
SD | 0.00 | 0.00 | 1.67 | |
Group 3 | Mean | 8.80 | 1.010 | 10.40 |
SD | 0.45 | 0.01 | 1.67 | |
Group 4 | Mean | 8.80 | 1.015 | 11.00 |
SD | 0.45 | 0.00 | 1.41 | |
Group 1R | Mean | 8.80 | 1.013 | 12.40 |
SD | 0.45 | 0.01 | 1.67 | |
Group 4R | Mean | 8.80 | 1.018 | 12.40 |
SD | 0.45 | 0.01 | 1.67 |
URINANALYSIS – FEMALES
TREATMENT (Week 4)
| pH | SPECIFIC GRAVITY | VOLUME | |
(pH) | (SG) | mL | ||
Group 1 | Mean | 8.80 | 1.011 | 12.40 |
SD | 0.45 | 0.01 | 1.67 | |
Group 2 | Mean | 9.00 | 1.011 | 10.00 |
SD | 0.00 | 0.01 | 1.67 | |
Group 3 | Mean | 8.80 | 1.013 | 10.80 |
SD | 0.45 | 0.01 | 2.28 | |
Group 4 | Mean | 8.80 | 1.010 | 9.60 |
SD | 0.45 | 0.01 | 1.14 | |
Group 1R | Mean | 8.80 | 1.010 | 10.00 |
SD | 0.45 | 0.01 | 1.67 | |
Group 4R | Mean | 8.80 | 1.013 | 11.40 |
SD | 0.45 | 0.01 | 1.95 |
ORGAN WEIGHTS (GRAM) – MALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 201.6 | 206.5 | 205.6 | 205.8 | 233.8 | 233.3 |
SD | 2.48 | 2.48 | 1.33 | 0.88 | 1.65 | 2.59 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain
| Mean | 1.7346 | 1.7108 | 1.6158 | 1.7310 | 1.6298 | 1.6892 |
SD | 0.10311 | 0.08949 | 0.13100 | 0.15775 | 0.15236 | 0.11628 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.7662 | 0.9258 | 0.8216 | 1.0210# | 0.9108 | 0.7960 |
SD | 0.16332 | 0.12457 | 0.07909 | 0.20868 | 0.16627 | 0.12221 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 7.2060 | 8.3154 | 8.3516 | 8.8132 | 9.3868 | 8.5660 |
SD | 3.53997 | 2.41791 | 1.32709 | 1.22586 | 4.82931 | 3.92057 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 1.1056 | 0.7510 | 1.0822 | 1.2202 | 0.9134 | 0.8304 |
SD | 1.11615 | 0.42077 | 0.41242 | 0.35144 | 0.64380 | 0.59054 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Kidneys
| Mean | 1.5062 | 1.7180 | 1.5344 | 1.7140 | 1.6102 | 1.6560 |
SD | 0.32228 | 0.32495 | 0.14521 | 0.23357 | 0.44694 | 0.40197 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Adrenals | Mean | 0.0558 | 0.0556 | 0.0550 | 0.0550 | 0.0534 | 0.0528 |
SD | 0.00691 | 0.00873 | 0.00919 | 0.00510 | 0.01656 | 0.01322 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Testes | Mean | 2.1732 | 2.2650 | 2.3306 | 2.5016 | 2.4852 | 2.4964 |
SD | 0.20189 | 0.36690 | 0.13797 | 0.40516 | 0.56094 | 0.26159 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Epididymes | Mean | 0.7882 | 0.9554 | 1.0426 | 1.1044 | 1.1042 | 1.0708 |
SD | 0.21886 | 0.40228 | 0.26590 | 0.41419 | 0.20895 | 0.05645 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.3498 | 0.3568 | 0.3510 | 0.4766 | 0.6034 | 0.2596 |
SD | 0.15497 | 0.12788 | 0.11518 | 0.05962 | 0.48764 | 0.09413 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Pro + Sem. Vesical with Coagulating glands | Mean | 0.6402 | 0.7834 | 0.6666 | 1.0854 | 0.8446 | 0.9298 |
SD | 0.19241 | 0.26254 | 0.26304 | 0.66523 | 0.50951 | 0.24046 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
# Significant at p ≥ 0.05 level with group 1
ORGAN WEIGHTS (GRAM) – SUMMARY FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | ||||
Body Weight (G) | Mean | 205.0 | 206.6 | 208.2 | 206.7 | 234.7 | 234.1 | |||
SD | 1.60 | 1.94 | 3.26 | 4.05 | 1.72 | 4.99 | ||||
N | 5 | 5 | 5 | 5 | 5 | 5 | ||||
Brain
| Mean | 1.6048 | 1.5174 | 1.4656 | 1.5704 | 1.6350 | 1.3958## | |||
SD | 0.06488 | 0.07779 | 0.25213 | 0.10088 | 0.04643 | 0.21369 | ||||
N | 5 | 5 | 5 | 5 | 5 | 5 | ||||
Heart | Mean | 0.6312 | 0.5936 | 0.6156 | 0.7820# | 0.6228 | 0.6962 | |||
SD | 0.08837 | 0.05679 | 0.08325 | 0.08404 | 0.10838 | 0.14596 | ||||
N | 5 | 5 | 5 | 5 | 5 | 5 | ||||
Liver | Mean | 6.0136 | 5.2958 | 5.2068 | 5.7436 | 5.5752 | 6.5608 | |||
SD | 1.01187 | 0.70639 | 0.74267 | 0.20056 | 0.70287 | 1.42551 | ||||
N | 5 | 5 | 5 | 5 | 5 | 5 | ||||
Spleen | Mean | 0.7854 | 0.5778 | 0.5220 | 0.7640 | 0.4272 | 0.8990 | |||
SD | 0.49005 | 0.09975 | 0.12471 | 0.38037 | 0.08106 | 0.65253 | ||||
N | 5 | 5 | 5 | 5 | 5 | 5 | ||||
Kidneys
| Mean | 1.1310 | 1.1960 | 1.0722 | 1.1430 | 1.1392 | 1.1034 |
| ||
SD | 0.23607 | 0.23121 | 0.09131 | 0.09180 | 0.10037 | 0.15315 |
| |||
N | 5 | 5 | 5 | 5 | 5 | 5 |
|
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Adrenals | Mean | 0.0594 | 0.0700 | 0.0622 | 0.0638 | 0.0568 | 0.0586 |
SD | 0.00635 | 0.01235 | 0.01295 | 0.01439 | 0.00642 | 0.01544 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Ovaries | Mean | 0.1120 | 0.1112 | 0.1040 | 0.0946 | 0.1098 | 0.1332 |
SD | 0.02102 | 0.00981 | 0.02233 | 0.01264 | 0.03997 | 0.00896 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Uterus | Mean | 0.2886 | 0.3960 | 0.3238 | 0.3164 | 0.3154 | 0.3800 |
SD | 0.07681 | 0.09858 | 0.15767 | 0.08780 | 0.04489 | 0.11493 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.3396 | 0.2238 | 0.2766 | 0.3476 | 0.2258 | 0.3510 |
SD | 0.16634 | 0.06073 | 0.06431 | 0.03428 | 0.06864 | 0.11910 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
# Significant at p ≥ 0.05 level with group 1, ##Significant at p≤0.05 level with group 1
ORGAN WEIGHTS RATIO (%) – MALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 201.6 | 206.5 | 205.6 | 205.8 | 233.8 | 233.3 |
SD | 2.48 | 2.48 | 1.33 | 0.88 | 1.65 | 2.59 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain
| Mean | 0.8606 | 0.8286 | 0.7857 | 0.8410 | 0.6969 | 0.7241 |
SD | 0.05237 | 0.04426 | 0.06274 | 0.07721 | 0.0618 | 0.0525 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.3798 | 0.4484 | 0.3994 | 0.4962 | 0.3896 | 0.3412 |
SD | 0.07968 | 0.06098 | 0.03717 | 0.10243 | 0.0709 | 0.0531 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 3.5679 | 4.0309 | 4.0602 | 4.2812 | 4.0087 | 3.6717 |
SD | 1.74103 | 1.19784 | 0.63616 | 0.59293 | 2.0455 | 1.6904 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 0.5464 | 0.3635 | 0.5258 | 0.5925 | 0.3896 | 0.3555 |
SD | 0.55140 | 0.20211 | 0.19879 | 0.16868 | 0.2729 | 0.2533 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Kidneys
| Mean | 0.7469 | 0.8327 | 0.7461 | 0.8327 | 0.6884 | 0.7101 |
SD | 0.15903 | 0.16386 | 0.06912 | 0.11382 | 0.1893 | 0.1754 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Adrenals | Mean | 0.0277 | 0.0269 | 0.0268 | 0.0267 | 0.0228 | 0.0226 |
SD | 0.00337 | 0.00419 | 0.00455 | 0.00240 | 0.0071 | 0.0056 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Testes
| Mean | 1.0777 | 1.0981 | 1.1336 | 1.2152 | 1.0626 | 1.0699 |
SD | 0.09411 | 0.18840 | 0.07181 | 0.19648 | 0.2373 | 0.1117 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Epididymes | Mean | 0.3907 | 0.4641 | 0.5071 | 0.5364 | 0.4724 | 0.4590 |
SD | 0.10679 | 0.20087 | 0.12960 | 0.20100 | 0.0894 | 0.0267 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.1735 | 0.1729 | 0.1709 | 0.2316 | 0.2580 | 0.1113 |
SD | 0.07688 | 0.06313 | 0.05658 | 0.02946 | 0.2081 | 0.0404 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Pro + Sem. Vesical with Coagulating glands | Mean | 0.3170 | 0.3784 | 0.3239 | 0.5275 | 0.3621 | 0.3981 |
SD | 0.09233 | 0.12309 | 0.12610 | 0.32423 | 0.2208 | 0.1008 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
ORGAN WEIGHTS RATIO (%) – FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 205.0 | 206.6 | 208.2 | 206.7 | 234.7 | 234.1 |
SD | 1.60 | 1.94 | 3.26 | 4.05 | 1.72 | 4.99 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain
| Mean | 0.7826 | 0.7344 | 0.7043 | 0.7603 | 0.6968 | 0.5953 |
SD | 0.02848 | 0.03509 | 0.12292 | 0.05660 | 0.0196 | 0.0827 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.3078 | 0.2873 | 0.2954 | 0.3785 | 0.2653 | 0.2971 |
SD | 0.04322 | 0.02761 | 0.03646 | 0.04176 | 0.0451 | 0.0599 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 2.9320 | 2.5637 | 2.5001 | 2.7790 | 2.3750 | 2.7960 |
SD | 0.48266 | 0.34348 | 0.34371 | 0.09393 | 0.2893 | 0.5609 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 0.3828 | 0.2799 | 0.2504 | 0.3721 | 0.1821 | 0.3811 |
SD | 0.23753 | 0.04973 | 0.05710 | 0.19166 | 0.0346 | 0.2708 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Kidneys
| Mean | 0.5512 | 0.5788 | 0.5152 | 0.5535 | 0.4856 | 0.4707 |
SD | 0.11164 | 0.11155 | 0.04645 | 0.05117 | 0.0441 | 0.0578 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Adrenals | Mean | 0.0290 | 0.0339 | 0.0298 | 0.0308 | 0.0242 | 0.0250 |
SD | 0.00321 | 0.00617 | 0.00607 | 0.00650 | 0.0026 | 0.0064 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
ovaries | Mean | 0.0546 | 0.0538 | 0.0499 | 0.0458 | 0.0468 | 0.0569 |
SD | 0.01026 | 0.00468 | 0.00997 | 0.00672 | 0.0171 | 0.0043 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Uterus
| Mean | 0.1408 | 0.1917 | 0.1555 | 0.1527 | 0.1343 | 0.1625 |
SD | 0.03780 | 0.04768 | 0.07629 | 0.04020 | 0.0184 | 0.0496 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus
| Mean | 0.1660 | 0.1084 | 0.1326 | 0.1685 | 0.0963 | 0.1493 |
SD | 0.08221 | 0.02991 | 0.02901 | 0.01953 | 0.0296 | 0.0479 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
GROSS PATHOLOGY
Male
Gross observation | Group | ||||
control (G1) | Low dose (G2) | Intermediate dose (G3) | High dose (G4) | ||
External | |||||
NAD | 5/5 | 5/5 | 5/5 | 5/5 | |
Internal | |||||
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Female
Gross observation | Group | |||
control (G1) | Low dose (G2) | Intermediate dose (G3) | High dose (G4) | |
External | ||||
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Internal | ||||
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Key: M – Male; F – Female; No. of animals showing observation/Total no. of animals
HISTOPATHOLOGY
ORGAN | OBSERVATIONS | Control (G1) | High dose (G4) | ||
M | F | M | F | ||
Liver | Sinusoidal Haemorrhage | 2/5 | 0/5 | 1/5 | 1/5 |
Foci of centrilobular/ Periportalnecrosis//Inflammation | 3/5 | 1/5 | 3/5 | 2/5 | |
No Abnormality Detected (NAD) | 1/5 | 4/5 | 2/5 | 2/5 | |
Lungs | Thickening of Alveolar wall/Alveolar Inflammation | 4/5 | 3/5 | 2/2 | 2/2 |
No Abnormality Detected (NAD) | 1/5 | 2/5 | 3/5 | 3/5 | |
Spleen | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Heart | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Aorta | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Kidney | Tubular Haemorrhage | 1/5 | 0/5 | 0/5 | 0/5 |
Tubular /interstitial inflammation | 1/5 | 1/5 | 1/5 | 1/5 | |
No Abnormality Detected (NAD) | 3/5 | 4/5 | 4/5 | 4/5 | |
Adrenals | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Brain | Foci of Cerebral Necrosis | 1/5 | 1/5 | 1/5 | 0/5 |
No Abnormality Detected (NAD) | 4/5 | 4/5 | 4/5 | 5/5 | |
Pituitary | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Thyroid and Para thyroid | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Trachea | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Oesophagus | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Jejunum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Duodenum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Ileum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Colon | Sub mucosal lymphoid tissue hyperplasia | 2/5 | 0/5 | 3/5 | 0/5 |
No Abnormality Detected (NAD) | 3/5 | 5/5 | 2/5 | 5/5 | |
Rectum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Caecum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Lymph nodes | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Pancreas | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Thymus | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Urinary bladder | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Testes | No Abnormality Detected (NAD) | 5/5 | - | 5/5 | - |
Epididymis | No Abnormality Detected (NAD) | 5/5 | - | 5/5 | - |
Prost+Seminal Vesicles+coagula Ting glands | No Abnormality Detected (NAD) | 5/5 | - | 5/5 | - |
Ovary | No Abnormality Detected (NAD) | - | 5/5 | - | 5/5 |
Uterus | No Abnormality Detected (NAD) | - | 5/5 | - | 5/5 |
Cervix+Vagina | No Abnormality Detected (NAD) | - | 5/5 | - | 5/5 |
Stomach | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Skeletal muscle | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Sciatic nerve | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Eye | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Spinal cord | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Sternum | No Abnormality Detected (NAD) | 5/5 | 5/5 | 5/5 | 5/5 |
Key: M – Male; F – Female; No. of animals showing observation/Total no. of animals.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 120 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is from a Klimisch 1 data source and provides a robust study summary.
- System:
- hepatobiliary
- Organ:
- liver
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation, other
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- exposure considerations
- Justification for data waiving:
- a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated Dose Toxicity (Oral):
A study according to the OECD Test Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents), performed using male and female Wistar Rats. The test chemical was administered via oral: gavage route. 5 animals per sex dose were used in the study. 6 groups were used in the study. The test chemical was administered in a dose range of 0, 30, 60 and 120 mg/kg bw/day as a control group, low dose, mid dose and high dose groups, respectively. Two recovery groups (0 mg/kg bw/day-Control Recovery and 1000 mg/kg bw/day-High Dose Recovery Group) were used in the study to observe the reversibility of the effects that would be observed in the main groups, if caused due to the test chemical. Distilled water was used as a vehicle. The test chemical was administered to the animals, once daily. The animals were dosed for 28 days, consecutively. The doses were selected on the basis of a Dose Range Finding (DRF) Study. In this study, the doses for the DRF study were 0, 50, 100 and 200 mg/kg bw/day. During the treatment 03 Males and 04 Females showed Mortality in High dose (200 mg/kg Body weight). There was no mortality in Control, Low Dose and Mid Dose. Piloerection and dullness were observed in High dose group. Hence, based on the Dose Range Finding Study, the doses of 30, 60 and 120 mg/kg body weight were confirmed for main study. As per the requirement according to OECD test guideline 407, animals was observed twice daily for morbidity and mortality while for Clinical Signs, Once daily during acclimatization phase and twice daily on first 3 days of treatment; once daily thereafter. During Recovery period, animals were observed once daily. Detailed clinical observations were done, once before the first exposure and weekly after. Body weights were examined once during Acclimatization and before randomization and Weekly Once during Treatment Period and Recovery Period. Also, feed consumption was observed Once weekly during treatment and recovery period. Opthalmoscopic examinations was performed once during acclimatization, during week 4 in all animals of groups 1 and 4. Blood samples for hematology and clinical biochemistry was collected from all animals under Isoflurane anesthesia system. The animals were placed individually in metabolic cages and fasted overnight before blood and urine sampling but allowed access to water ad libitum. Urine samples were collected in the morning before the blood collection. Blood samples were collected in the morning to reduce biological variation caused by circadian rhythms. Blood samples were drawn from the retro-orbital plexus using a micro-hematocrit heparinized glass capillary tube. Blood samples were centrifuged and plasma was separated for clinical biochemistry analysis. Examinations for functional observational battery was performed by end of week 4 for main groups and by the end of week 6 for recovery groups. Necropsy and histopathology was done on day 29 and day 43 for main group and recovery group animals, respectively. It was observed that, No clinical signs were observed in all the dose groups examined including the recovery groups. No mortality was observed in all the dose groups examined including the recovery groups. No adverse effect on body weight was observed for treated groups when compared with control group. No significant and toxicological relevant changes in the body weight between treated and control group were observed. No significance in the feed consumption was observed in any of the treated and recovery groups when compared with vehicle control group. No effects were observed after ophthalmological examinations in both the control groups and treatment groups. No treatment related effects were observed in the both male and female animals with respect to hematological parameters viz RBC, WBC Hb, MCV, MCHC, PCV, PT and APTT when compared with control group. However, in the treatment group, Platelets count was increased in Low Dose (G2), Intermediate Dose (G3) and high dose (G4) group male rats when compared with control group was observed and in high dose recovery group females Monocytes count was decreased comparable with control. This significance may not be attributed to treatment since all the hematological values fall within the normal biological range and no biological significance was noted. There was no dose related effect on few biochemical parameters. There was a significant decrease in both Asparate aminotransferase (AST) and Alanine aminotransferase (ALT) levels in males. Significant changes were observed indicating the test chemical's effect on liver. In males, Urea levels, Bilirubin levels decreased, while Potassium levels increased in low dose group. In Mid Dose Group, Bilirubin levels decreased, while alkaline phosphatase levels and Potassium levels increased, when compared with the control group. In females, Glucose and Sodium levels increased in High dose group, while cholesterol and triglyceride levels decreased, when compared with control group. No significant changes were observed in any of the treated groups and recovery group. No test chemical related effects on the grip strength, motor activity, sensory activity was noted in both treated and recovery group animals. Both in males and females when organ weights of Heart increased High dose group (G4) compared with control group. In Recovery group Females, organ weights of Brain decreased High dose group (G4), when compared with control group. During necropsy, macroscopic lesions were observed on liver and lungs where hemorrhagic spots were observed in both the organs in high dose group. Apart from these observations, no other treatment related macroscopic finding in any of the animals in all groups including Systemic and Reproductive organs. In microscopic observations, sinusoidal hemorrhages were observed in liver in control males, but such effect was observed in both the sexes in high dose group. Also, Foci of necrosis/inflammation of hepatocytes were observed in centri lobular of liver in three male and two female animals from G4 group. Alveolar wall thickening or alveolar inflammation noticed in the lungs of two male and two female animals from G4 group. Thus, based on all the available data, it was concluded that after repeated exposures of the test chemical via oral route, it caused adverse effects on hepatobiliary system. Therefore, the NOAEL and LOAEL for the test chemical was 60 and 120 mg/kg bw/day, respectively after 28 days of exposure.
Repeated Dose Toxicity (Inhalation):
According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the test chemical which is reported as 6.600541739463232e-8 mmHg at 25 degree Celsius. Also, considering the particle size distribution of the substance the majority of the particles was found to be in the range size of 150 micron to 106 micron which is much larger size range compared to the inhalable particulate matter .Thus, exposure to inhalable dust, mist and vapour of the test chemical is highly unlikely. Therefore this study is considered for waiver.
Repeated Dose Toxicity (Dermal):
The acute toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that the test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that the test chemical shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Based on the available data for the test chemical, it is concluded that the test chemical does exhibits adverse effects on liver and lungs after repeated exposures by oral routes by oral route, while the test chemical is not likely to be exposed repeatedly via inhalation and dermal route. Therefore, based on all the available data, it is concluded that the test chemical is likely to be classified as STOT-RE 2 as per the values mentioned in CLP criteria of classification and labeling.
Justification for classification or non-classification
Based on the available data for the test chemical, it is concluded that the test chemical does exhibits adverse effects on liver and lungs after repeated exposures by oral routes by oral route, while the test chemical is not likely to be exposed repeatedly via inhalation and dermal route. Therefore, based on all the available data, it is concluded that the test chemical is likely to be classified as STOT-RE 2 as per the values mentioned in CLP criteria of classification and labeling.
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