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EC number: 271-524-7 | CAS number: 68583-95-9 This substance is identified in the Colour Index by Colour Index Constitution Number, C.I. 16035:1.
- 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 oral
The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.
Repeated Inhalation:
The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical[The estimated vapor pressure of the test chemical was 3.86*10-21 Pa]. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.
Repeated dermal:
The acute dermal median lethal dose (LD50) of test chemical was considered to be >2000 mg/kg body weight. The test chemical did not cause any dermal reactions to humans and rats in the skin sensitization as well skin irritation studies respectively. Hence, it can be expected that the test chemical shall not exhibit 28 day repeated dose toxicity via dermal route. Hence, this endpoint 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:
- chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- Weight of evidence approach based on various test chemicals
- Justification for type of information:
- Weight of evidence approach based on various test chemicals
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Qualifier:
- according to guideline
- Guideline:
- other: Weight of evidence approach based on various test chemicals
- Principles of method if other than guideline:
- Weight of evidence approach based on various test chemicals. The study 2,3 are referred as study 1,2
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: 1. Sprague Dawley; 2. Fischer 344
- Sex:
- male/female
- Route of administration:
- oral: feed
- Vehicle:
- other: 1. Purina Laboratory Chow; 2. test substance contained in the diet
- Details on oral exposure:
- 1. PREPARATION OF DOSING SOLUTIONS: The test material was incorporated into the basal diet using a Patterson-Kelley twin shell blender and used at dose levels of 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day males and 0, 228, 901, 3604 mg/kg bw/day for females)
DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared and presented weekly.
- Mixing appropriate amounts with (Type of food): Purina
Laboratory Chow
- Storage temperature of food: No data
VEHICLE
- Justification for use and choice of vehicle (if other than water): Purina Laboratory Chow
- Concentration in vehicle: 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day males and 0, 228, 901, 3604 mg/kg bw/day for females)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
2. PREPARATION OF DOSING SOLUTIONS: Not applicable
DIET PREPARATION
- Rate of preparation of diet (frequency):ones in 4 days
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow animal meal
- Storage temperature of food:
VEHICLE
- Justification for use and choice of vehicle (if other than water): Not available
- Concentration in vehicle: Not available
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 2. The stability of diets formulated with 100,000 ppm dye was determined by analyses performed after storage for 2 weeks at -20 , 5 , 25 , or 45 degree C. Spectrophotometric analysis of water extracts of
the diets indicated that the test chemical was stable in feed for 2 weeks at temperatures up to 45 degree C - Duration of treatment / exposure:
- 1. Males: 118 weeks
Females: 121 weeks
2. 103 weeks - Frequency of treatment:
- 1. 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods
2. daily - Remarks:
- Males: 0.0, 0.37, 1.39 and 5.19% (0, 180, 701, 2829 mg/kg bw/day)
Females: 0.0, 0.37, 1.39 and 5.19% (0, 228, 901, 3604 mg/kg bw/day - Remarks:
- Doses / Concentrations:
0,1250 mg/kg,2500 mg/kg - No. of animals per sex per dose:
- 1. 30/sex/group
2. Control-90 male and 90 female
1250 mg/kg-50 male and 50 female
2500 mg/kg-50 male and 50 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- 1. The dietary concentrations for this study were selected based on the results of previous subchronic studies in rats
2. - Dose selection rationale: Dose selected on the basis of Range-Finding and 14-Day Repeated Dose Studies and Subchronic Studies.
Range-Finding and 14-Day Repeated Dose Studies: In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.
The low and high dietary levels of the test chemical selected for the chronic study with rats were 12,500 and 25,000 ppm.
- Rationale for animal assignment (if not random):Not available
- Rationale for selecting satellite groups: Not available
- Post-exposure recovery period in satellite groups: Not available
- Section schedule rationale (if not random): Not available - Observations and examinations performed and frequency:
- 1. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: gross signs of toxicity, death and morbidity were recorded daily. The rats were observed twice daily (5 days/wk) during the last 6 months of the study to minimize the loss of tissue to autolysis in rats that died on test.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly for wk 0 10, bi-weekly for wk 12-26, and every 4 wk thereafter
BODY WEIGHT: Yes
- Time schedule for examinations: weekly for wk 0 10, bi-weekly for wk 12 26, and every 4 wk thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):Yes weekly for wk 0 10, bi-weekly for wk 12 26, and every 4 wk thereafter
FOOD EFFICIENCY: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Blood samples were obtained from the tail vein during the study, and from the abdominal aorta at termination test were conducted at wk 13, 26, 52 and 78 and at termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: five rats/sex/group
- Parameters checked : haematocrit, haemoglobin, erythrocyte count, and total and differential leucocyte counts.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Blood samples were obtained from the tail vein during the study, and from the abdominal aorta at termination and clinical chemistry studies were performed on at week 52 and at termination
- Animals fasted: No data
- How many animals: 5 rats/sex/group
- Parameters checked: aspartate aminotransferase, Alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, fasting glucose, total protein, sodium, potassium, chloride, carbon dioxide (termination only) and serum electrophoresis
URINALYSIS: Yes
- Time schedule for collection of urine: Urine samples were obtained by housing rats overnight in individual metabolism cages. Urinary analysis was conducted at wk 13, 26, 52, 78 and at termination
- Metabolism cages used for collection of urine: Yes
- Animals fasted: No data
- Parameters checked : specific gravity, pH, glucose, ketones, total protein, bilirubin and sediment.
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER:
2. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations : observations of sick, tumorbearing, and moribund animals were recorded
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Each month
BODY WEIGHT: Yes
- Time schedule for examinations:Monthly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
FOOD EFFICIENCY: No data
- 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: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data
OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
HAEMATOLOGY: Not examined
- Time schedule for collection of blood: Not examined
- Anaesthetic used for blood collection: Not examined
- Animals fasted: Not examined
- How many animals: Not examined
- Parameters checked in table [No.?] were examined. Not examined
CLINICAL CHEMISTRY: Not examined
- Time schedule for collection of blood: Not examined
- Animals fasted: Not examined
- How many animals: Not examined
- Parameters checked in table [No.?] were examined. Not examined
URINALYSIS: No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined.: No data
NEUROBEHAVIOURAL EXAMINATION: Not examined
- Time schedule for examinations: Not examined
- Dose groups that were examined: Not examined
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not examined - Sacrifice and pathology:
- 1. GROSS PATHOLOGY: Yes
Gross autopsies were conducted on all rats that died spontaneously, were killed in a moribund condition, or were killed at the end of the study. Rats were killed by exsanguination under sodium pentobarbital. Absolute and relative organ weights were determined for the heart, liver, spleen, kidneys, testes with epididymides, and thyroid and adrenal glands.
HISTOPATHOLOGY: Yes
Complete histology was conducted on all rats from the control and high-dose groups. The following tissues from these rats were examined histologically: brain, pituitary, thoracic spinal cord, eyes, oesophagus, thyroid, thymus, heart, lungs, liver, spleen, pancreas, stomach, small and large intestine, mesenteric lymph node, kidneys, adrenal, urinary bladder, uterus, prostate, ovaries, testes with epididymides, seminal vesicles, skin, rib junction, bone marrow, nerve with muscle, and any tissue masses or lesions. Histology was also conducted on animals from any group with grossly observed masses or lesions. If a potential effect was consistently noted in a tissue then that tissue was examined histologically in all rats. All excised tissues not exhausted for histology were preserved.
2. GROSS PATHOLOGY: Yes
Animals were killed using carbon dioxide and necropsied.
HISTOPATHOLOGY: Yes
Neoplastic and Non neoplastic lesions examined microscopically
The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses. - Statistics:
- 1. Gain in group mean body weight and total food consumption for weeks 0-54, group mean body weight at termination, and absolute and relative organ weights were analysed by the methods of Bartlett (1937), Snedecor and Cochran (1967) and Scheffe (1953). Survival data were analysed by the methods of Sachs (1959) and Snedecor and Cochran (1967). Tumour incidence data were analysed by the methods described by Thomas et al. (1977). All analyses were considered
significant at P <0.05. Time-to-tumour analyses were not performed because data correlating the time of tumour development to the time of death were not
generated.
2.
1.Probabilities of survival were estimated by the product-limit procedure of Kaplan and Meier.
2. Possible dose-related effect on survival- method of Cox
3. Dose-related trend- Tarone's extensions of Cox's.
4.P values less than 0.05
5. Comparition of the tumor incidence One-tailed Fisher exact test.
6. For linear trend in proportions, with continuity correction- Cochran-Armitage test. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- 1. Localized hair loss (apparently due to friction against the cage) and nasal and ocular discharge occurred at low incidences throughout the study in control and treated rats. A red tint to the fur was noted in treated rats, and the faeces of mid- and high-dose rats were red. Palpable masses were noted with equal incidences in the control and treated groups.
- Mortality:
- no mortality observed
- Description (incidence):
- 1. There were no compound-related effects on survival
2. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)). - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- 1. Group mean body weights at the end of the study were decreased in rats that received FD & C Red No. 40 except for the mid-dose 701 mg/Kg bw/day males, in which they were increased.The mean body weight of the high-dose 3604 mg/Kg bw/day females at the end of the study was significantly less than that of the controls.
2. The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- 1. Food consumption were increased in 2829 mg/Kg bw/day foe males and 3604 mg/Kg bw/day for females in the treated group but not significantly so as compared to control
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- 1. Few of the hematological differed significantly between control and treated rats, and none of the differences were compound related.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- 1. Few of the Clinical chemistry differed significantly between control and treated rats, and none of the differences were compound related.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- 1. Few of the urinanalysis differed significantly between control and treated rats, and none of the differences were compound related.
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- 1. No compound-related changes in organ weights, were noted in rats that died on test or that were killed in a moribund state or at the end of the study.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- 1. No compound related adverse effect observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- 1. Histological evaluation revealed a variety of lesions, including neoplasm, among the control and treated rats.
The lesions were present at similar incidences in control and treated rats and appeared to be spontaneous. None of the lesions were determined to be related to the administration of the test chemical
2. Histopathological examination revealed no evidence of carcinogenicity related to treatment with the test material. No other effects were reported.No compound-related neoplastic or non-neoplastic lesions were observed in the rats - Histopathological findings: neoplastic:
- not specified
- Description (incidence and severity):
- 2. No compound-related neoplastic or non-neoplastic lesions were observed in the rats
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- > 900 - <= 1 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- gross pathology
- mortality
- organ weights and organ / body weight ratios
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- Conclusions:
- The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.
- Executive summary:
Repeated oral
Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:
Study 1:
Combined repeated dose and carcinogenicity study was performed on Sprague Dawley rats to determine its toxicity.
30 Sprague Dawley rats per sex per dose group were fed the test chemical in diet at dose concentration of 0, 0.37, 1.39 or 5.19% (0, 180, 701, 2829 mg/kg bw/day for males and 0, 228, 901, 3604 mg/kg bw/day for females), 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods. The animals were observed for clinical signs, mortality, morbidity, body weight and food consumption changes, hematology, clinical chemistry, gross and histopathology.
No significant compound related adverse effect were observed on mortality, clinical signs, body weight (except for a reduction in body weight in high-dose 3604 mg/Kg bw/day females at the end of the study), food consumption, hematology, clinical chemistry, gross and histopathology.
The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.
Study 2:
A combined repeated dose toxicity and carcinogenesis study was conducted using groups of 50 male and 50 female F344 rats which were fed diets containing 1250 or 2500 mg/kgbw/day of the test chemical for 103 weeks. Groups of 90 male and 90 female rats served as undosed controls.
The doses for the study were decided on the basis of a single day and sub chronic dose studies.In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.
Based on the single dose and subchronic study, 0,1250 mg/kg,2500 mg/kg were the concentrations of the test and control groups when dosed with the test chemical for 103 weeks. All animals were observed twice daily, and observations of sick, tumorbearing, and moribund animals were recorded. Clinical examination and palpation for masses were performed each month, and the animals were weighed at least monthly. Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead. The tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses. Necropsies were performed on all animals found dead, unless precluded in whole or in part by autolysis or cannibalization. Thus, the number of animals from which particular organs or tissues were examined microscopically varies and does not necessarily represent the number of animals that were placed on study in each group.
Throughout the study, mean body weights of high-dose female rats and all low-dose groups were comparable with those of the controls, but mean body weights of high-dose male rats were slightly lower (10% or less) than those of the controls. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)). The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study. No compound-related neoplastic or non-neoplastic lesions were observed in the rats.
Therefore, the No Observed Effect level[ NOAEL] was considered to be 1250 mg/kg and 2500 mg/kg for males and females, respectively, based on the effects observed on mean body weight, survival rate and histopathology.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 900 mg/kg bw/day
- Study duration:
- chronic
- Experimental exposure time per week (hours/week):
- 168
- Species:
- rat
- Quality of whole database:
- Klimisch Rating 2- data is from peer reviewed journals
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- 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
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
Additional information
Repeated oral
Data available from different studies were reviewed to determine the repeated dose oral toxicity of test chemical. The studies are as mentioned below:
Study 1:
Combined repeated dose and carcinogenicity study was performed on Sprague Dawley rats to determine its toxicity.
30 Sprague Dawley rats per sex per dose group were fed the test chemical in diet at dose concentration of 0, 0.37, 1.39 or 5.19% (0, 180, 701, 2829 mg/kg bw/day for males and 0, 228, 901, 3604 mg/kg bw/day for females), 1 wk before mating, throughout the 3-wk breeding period, and during the gestation and lactation periods. The animals were observed for clinical signs, mortality, morbidity, body weight and food consumption changes, hematology, clinical chemistry, gross and histopathology.
No significant compound related adverse effect were observed on mortality, clinical signs, body weight (except for a reduction in body weight in high-dose 3604 mg/Kg bw/day females at the end of the study), food consumption, hematology, clinical chemistry, gross and histopathology.
The No observed adverse-effect level (NOAEL) in this study was 5.19% (2829 mg/kg bw/day) for male rats, and 1.39% (901 mg/kg bw/day) for female rats.
Study 2:
A combined repeated dose toxicity and carcinogenesis study was conducted using groups of 50 male and 50 female F344 rats which were fed diets containing 1250 or 2500 mg/kgbw/day of the test chemical for 103 weeks. Groups of 90 male and 90 female rats served as undosed controls.
The doses for the study were decided on the basis of a single day and sub chronic dose studies.In the single day dosing study, groups of five males and females of each rats were fed diets containing 6,000, 12,500, 25,000, 50,000, 100,000, or 200,000 ppm of the test chemical for 24 hours and then lab chow for 13 days. In the repeated dose study, similar groups of rats were fed diets containing 6,000, 12,500, 25,000, 50,000 or 100,000 ppm of the test chemical for 2 weeks. No deaths occurred among the rats in either study.
Based on the single dose and subchronic study, 0,1250 mg/kg,2500 mg/kg were the concentrations of the test and control groups when dosed with the test chemical for 103 weeks. All animals were observed twice daily, and observations of sick, tumorbearing, and moribund animals were recorded. Clinical examination and palpation for masses were performed each month, and the animals were weighed at least monthly. Gross and microscopic examinations were performed on major tissues, major organs, and all gross lesions from killed animals and from animals found dead. The tissues were preserved in 10% neutral buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The following tissues were examined microscopically: skin (abdominal), lungs and bronchi, trachea, bone, bone marrow (femur) and thigh muscle, spleen, lymph nodes, thymus, heart, salivary glands, liver, pancreas, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, kidney, urinary bladder, pituitary, adrenal, thyroid, parathyroid, testis, prostate, mammary gland, uterus, ovary, brain, epididymus, eye, and all tissue masses. Necropsies were performed on all animals found dead, unless precluded in whole or in part by autolysis or cannibalization. Thus, the number of animals from which particular organs or tissues were examined microscopically varies and does not necessarily represent the number of animals that were placed on study in each group.
Throughout the study, mean body weights of high-dose female rats and all low-dose groups were comparable with those of the controls, but mean body weights of high-dose male rats were slightly lower (10% or less) than those of the controls. The survival of male and female rats was similar between treated animals and controls (males: control 70/90 (78%); low dose 36/50 (72%); and high dose 38/50 (76%) and females: control 66/88 (75%); low dose 40/50 (80%) and high dose 37/50 (74%)). The mean body weights of male rats administered the high dose were slightly lower than the control animals throughout the study. No compound-related neoplastic or non-neoplastic lesions were observed in the rats.
Therefore, the No Observed Effect level[ NOAEL] was considered to be 1250 mg/kg and 2500 mg/kg for males and females, respectively, based on the effects observed on mean body weight, survival rate and histopathology.
Repeated Dose Inhalation
The short term toxicity study need not be conducted because exposure to humans via inhalation route is not likely taking into account due to the low vapour pressure of the test chemical[The estimated vapor pressure of the test chemical was 3.86*10-21 Pa]. Thus, exposure to inhalable dust, mist and vapour of the chemical is highly unlikely. Therefore this study is considered for waiver.
Repeated dermal
The acute dermal median lethal dose (LD50) of test chemical was considered to be >2000 mg/kg body weight. The test chemical did not cause any dermal reactions to humans and rats in the skin sensitization as well skin irritation studies respectively. Hence, it can be expected that the test chemical shall not exhibit 28 day repeated dose toxicity via dermal route. Hence, this endpoint was considered for waiver.
Justification for classification or non-classification
Based on the available studies, the test chemical can be considered to be not toxic when exposed repeated via oral route. Hence, it can be classified under the category "Not Classified" as per CLP Regulation.
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