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EC number: 261-873-3 | CAS number: 59709-10-3
- 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
The No Observed Adverse Effect Level (NOAEL) was considered to be 1250 mg/kg/day, when rodents were treated with the given test chemical during repeated dose toxicity study.
Repeated dose toxicity: Inhalation
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. Also, the given test chemical has very low vapor pressure 2.493128e-10 Pa, so the potential for the generation of inhalable vapors is very low. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver.
Repeated dose toxicity: Dermal
A short-term toxicity study does not need to be conducted because exposure of humans via dermal in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the acute dermal toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. 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 test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 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:
- 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:
- Experimental data from various test chemicals
- Justification for type of information:
- Weight of evidence approach based on the available information from 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: As mentioned below
- Principles of method if other than guideline:
- WoE report is based on 2 repeated dose toxicity studies i.e. WoE-2 and WoE-3.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: 2. Fischer 344 3. Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 2. TEST ANIMALS
- Source: Frederick Cancer Research Center (Frederick, MD)
- Age at study initiation: 56 days old
- Housing: rats were housed five per cage. Cages were rotated vertically once every two weeks.
- Diet (e.g. ad libitum): NIH-07 Rat, meal (Zeigler Bros., Inc., Gardners, PA), available ad libitum
- Water (e.g. ad libitum): Tap water (Birmingham Water Works) in glass water bottles with stainless steel sippers (Edstrom Automatic Watering Systems, Waterford, WI), available ad libitum
- Acclimation period: 20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8° C-25.6° C
- Humidity (%): 15%-85%
- Air changes (per hr): minimum 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours/day
3. TEST ANIMALS
- Source: No data
- Age at study initiation: 9 weeks - Route of administration:
- other: 2. oral: feed 3. oral: gavage
- Vehicle:
- other: 2. NIH-07 rat ration 3. water
- Details on oral exposure:
- 2. PREPARATION OF DOSING SOLUTIONS: No data available
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): premix of NIH-07 rat ratioon as meal, with the appropriate amount of C.I. Pigment Red 23.
- Storage temperature of food: 2 weeks for 45 °C
-Other information:The dose formulations were prepared by mixing appropriate quantities of C.1. Pigment Red 23 with feed (NIH-07 Rat Ration) to form a premix, then the remaining feed was added and mixed in a twin-shell blender equipped with an intensifier bar. Studies conducted by the analytical chemistry laboratory to determine stability and homogeneity of the dosed feed formulations indicated that the formulations were homogeneous and stable for at least 2 weeks at temperatures up to 45° C when stored in the dark. The preparations protected from light were stored at 5° C prior to use and at room temperature during use. Storage time was not more than 14 days. Periodic analyses of the dosed-feed formulations were conducted at the study laboratory and at the analytical chemistry laboratory throughout the studies. The original method used the extraction solvent nitrobenzene; the solventwas changed to a solution of 10 g potassium hydroxide in 500 mL methanol diluted to 1,000 mL with tetrahydrofuran because of inconsistent recoveries.
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0, 10,000, 25,000, or 50,000 ppm ((500, 1250 or 2500 mg/kg))
- Amount of vehicle (if gavage): Not applicable.
- Lot/batch no. (if required): Lot UB2158
- Purity: 99.6%.
3. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with water at dose levels of 0, 40, 200 or 1000 mg/Kg/day (Recovery group: 0, 1000 mg/kg/day)
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 0, 40, 200 or 1000 mg/Kg/day (Recovery group: 0, 1000 mg/kg/day) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 2. Dose levels were determined using visible spectroscopy at 478 nm. Homogeneity of the formulations was confirmed by the study laboratory. For the 2-year studies, a total of 142 samples were analyzed and five were remixed in order to be within acceptable limits.Periodically, the dose formulations were sent for referee analyses by MRI. The results from the study laboratory and from the referee analytical chemistry laboratory were generally in good agreement, with all value differences less than 13%
3. not specified - Duration of treatment / exposure:
- 2. 2years
3. Male: 42 days / - Female: 41 - 47 days - Frequency of treatment:
- 2. Daily
3. Daily - Remarks:
- 2. 0, 10,000, 25,000, or 50,000 ppm (0, 500, 1250 or 2500 mg/kg/day)
3. Test group: 0, 40, 200 or 1000 mg/Kg/day
Recovery group: 0, 1000 mg/kg/day - No. of animals per sex per dose:
- 2. 10 animals/dose
3. No data - Control animals:
- yes, concurrent vehicle
- Details on study design:
- 2. Details on study design:
- Dose selection rationale: Because levels of C.I. Pigment Red 23 as high as 2500 or 50,000 mg/kg in the feed did not adversely affect survival and mean body weights in the 17-day and 13-week studies, nor cause any chemical-related lesions, doses of 0, 500, 1250, or 2500 mg/kg were selected for the 2-year studies.
3. No data - Positive control:
- Not specified
- Observations and examinations performed and frequency:
- 2. Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice/day
- Cage side observations checked in table [No.?] were included. No data available
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at each weight check and at terminal sacrifice.
BODY WEIGHT: Yes
- Time schedule for examinations: once/week for 13 weeks, once/month thereafter and at sacrifice.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data available
- Animals fasted: No data available - How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: No data available sensory activity / grip strength / motor activity / other: No data available
3. CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data
BODY WEIGHT: Yes
- Time schedule for examinations: No data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- 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:
- 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: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data
URINALYSIS: Yes
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data
OTHER: No data - Sacrifice and pathology:
- 2. GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
3. GROSS PATHOLOGY: Yes. Organ weight was noted
HISTOPATHOLOGY: No data - Statistics:
- 2. Mean ± standard deviation was observed.
3. No data - Clinical signs:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - There were no clinical findings in rats considered to be chemically related.
3. no effects observed - Mortality:
- no mortality observed
- Description (incidence):
- 2. no mortality observed - No mortality were observed at all treated group 500, 1250 or 2500 mg/kg compare to control.
3. not specified - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - Male: Mean body weights of male rats were similar to that of the controls throughout the 2-year study
Female: from week 20 to the end of the study, the mean body weights of mid- and high-dose females were consistently lower than that of the controls
3. no effects observed - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - Feed consumption by exposed male and female rats was similar to that of to the controls.
3. no effects observed - 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):
- 2. no effects observed - In male rats, there were no biologically significant differences in hematology parameters related to chemical exposure.
In female rats, Hematocrit values, hemoglobin concentration, and erythrocyte counts interim evaluation were significantly less than those of the controls and serum total bilirubin was significantly increased in 50000 ppm female rats at the 15-month
3. no effects observed - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- 2. no effects observed - In male rats, there were no biologically significant differences in clinical chemistry parameters related to chemical exposure.
3. no effects observed - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- 2. not specified
3. no effects observed - Behaviour (functional findings):
- not specified
- Description (incidence and severity):
- 2. not specified
3. no effects observed - Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- 2. not specified
3. no effects observed - Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2. effects observed, treatment-related - A slightly increased incidence of mitosis, and invasion of adjacent renal tissue by tumor cells and Kidney: nephropathy was observed.
Pituitary Gland: Adenoma or carcinoma (Combined) of the pars distalis occurred with a significant negative trend in female rats. The incidence in the high-dose group was significantly lower than in the control.
Lymphoid Tissue: Red pigment, presumably compound- related, was observed in the lymphoid tissue of the small intestine in females and in the mesenteric lymph nodes in males. There was a dose-related increase in the amount of pigment present. The pigment consisted of distinct red granules or small elongated crystals within the cytoplasm of the macrophages.
3. no effects observed - Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- 2. not specified
3. no effects observed - Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Remarks:
- 2
- Effect level:
- 1 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- haematology
- histopathology: non-neoplastic
- mortality
- Remarks on result:
- other: No toxic effect were observed
- Dose descriptor:
- NOAEL
- Remarks:
- 3
- Effect level:
- 1 000 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: neoplastic
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- urinalysis
- Remarks on result:
- other: No adverse effects were noted at the mentioned dose level
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) was considered to be 1250 mg/kg/day, when rats were treated with the given test chemical during repeated dose toxicity study.
- Executive summary:
Data available from the various sources was reviewed to determine the toxic nature of the given test chemical. The studies are as mentioned below:
Two year repeated dose toxicity study was conducted by administering the given test chemical to male and female rats at doses of 0, 500, 1250, and 2500 mg/kg in feed for 103 weeks. All animals were observed twice daily. Clinical findings for rats were noted and recorded during body weight measurements and at sacrifice. Body weights were recorded weekly for the first 13 weeks, and then every four weeks until the end of the study; body weights were also recorded at the end of the study. Feed consumption was recorded daily per cage. Complete necropsies were performed on all animals. During necropsy all organs and tissues were examined for grossly visible lesions. Tissues for microscopic examination were preserved in 10% neutral buffered formalin and routinely processed for microscopic examination (embedded in paraffin, sectioned at 4-5 microgram, and stained with hematoxylin and eosin). Complete histopathologic evaluation was performed on animals from the control and high-dose group, on selected tissues, and on target organs and gross lesions from low- and mid-dose animals. Mean ± standard deviation was observed. No mortality was observed at all treated groups 500, 1250 or 2500 mg/kg compare to control. There were no clinical findings in rats considered to be chemically related. Mean body weights of male rats were similar to that of the controls throughout the 2-year study. From week 20 to the end of the study, the mean body weights of mid- and high-dose females were consistently lower than that of the controls. Feed consumption by exposed male and female rats was similar to that of to the controls. In male rats, there were no biologically significant differences in hematology parameters related to chemical exposure. In female rats, Hematocrit values, hemoglobin concentration, and erythrocyte counts interim evaluation were significantly less than those of the controls and serum total bilirubin was significantly increased in 2500 mg/kg female rats at the 15-month. In male rats, there were no biologically significant differences in clinical chemistry parameters related to chemical exposure. A slightly increased incidence of mitosis and invasion of adjacent renal tissue by tumor cells and Kidney: nephropathy was observed. In Pituitary Gland, adenoma or carcinoma (Combined) of the pars distalis occurred with a significant negative trend in female rats. The incidence in the high-dose group was significantly lower than in the control. In lymphoid Tissue, red pigment, presumably compound- related, was observed in the lymphoid tissue of the small intestine in females and in the mesenteric lymph nodes in males. There was a dose-related increase in the amount of pigment present. The pigment consisted of distinct red granules or small elongated crystals within the cytoplasm of the macrophages. Mononuclear cell leukemia occurred with a decreased incidence in male and female rats. Under the condition of the study, the NOAEL value for repeated dose toxicity of the given test chemical in male and female F344 rats was considered to be 1250 mg/kg/day.
In another study, the given test chemical was assessed for its possible toxic potential. For this purpose, Combined repeated dose and reproduction / developmental screening was performed as per OECD Guideline 422. Male and female Crl:CD (SD) rats were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, functional battery observations, body weight, food consumption, urinanalysis, hematology, blood chemistry, organ weight changes and histopathology. No adverse effects were noted in the various parameters studied. Based on the observations made, No Observed Adverse Effect Level (NOAEL) for the given test chemical was considered to be 1000 mg/Kg/day.
Thus based on the above studies, the No Observed Adverse Effect Level (NOAEL) was considered to be 1250 mg/kg body weight/day and hence is not likely to classify for repeated oral toxicity as per the criteria mentioned in CLP regulation.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 250 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from handbook or collection of data.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- other justification
- 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
- Quality of whole database:
- Waiver
Repeated dose toxicity: inhalation - local effects
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:
- other justification
- 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
- Quality of whole database:
- Waiver
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: Oral
Data available from the various sources was reviewed to determine the toxic nature of the given test chemical. The studies are as mentioned below:
Two year repeated dose toxicity study was conducted by administering the given test chemical to male and female rats at doses of 0, 500, 1250, and 2500 mg/kg in feed for 103 weeks. All animals were observed twice daily. Clinical findings for rats were noted and recorded during body weight measurements and at sacrifice. Body weights were recorded weekly for the first 13 weeks, and then every four weeks until the end of the study; body weights were also recorded at the end of the study. Feed consumption was recorded daily per cage. Complete necropsies were performed on all animals. During necropsy all organs and tissues were examined for grossly visible lesions. Tissues for microscopic examination were preserved in 10% neutral buffered formalin and routinely processed for microscopic examination (embedded in paraffin, sectioned at 4-5 microgram, and stained with hematoxylin and eosin). Complete histopathologic evaluation was performed on animals from the control and high-dose group, on selected tissues, and on target organs and gross lesions from low- and mid-dose animals. Mean ± standard deviation was observed. No mortality was observed at all treated groups 500, 1250 or 2500 mg/kg compare to control. There were no clinical findings in rats considered to be chemically related. Mean body weights of male rats were similar to that of the controls throughout the 2-year study. From week 20 to the end of the study, the mean body weights of mid- and high-dose females were consistently lower than that of the controls. Feed consumption by exposed male and female rats was similar to that of to the controls. In male rats, there were no biologically significant differences in hematology parameters related to chemical exposure. In female rats, Hematocrit values, hemoglobin concentration, and erythrocyte counts interim evaluation were significantly less than those of the controls and serum total bilirubin was significantly increased in 2500 mg/kg female rats at the 15-month. In male rats, there were no biologically significant differences in clinical chemistry parameters related to chemical exposure. A slightly increased incidence of mitosis and invasion of adjacent renal tissue by tumor cells and Kidney: nephropathy was observed. In Pituitary Gland, adenoma or carcinoma (Combined) of the pars distalis occurred with a significant negative trend in female rats. The incidence in the high-dose group was significantly lower than in the control. In lymphoid Tissue, red pigment, presumably compound- related, was observed in the lymphoid tissue of the small intestine in females and in the mesenteric lymph nodes in males. There was a dose-related increase in the amount of pigment present. The pigment consisted of distinct red granules or small elongated crystals within the cytoplasm of the macrophages. Mononuclear cell leukemia occurred with a decreased incidence in male and female rats. Under the condition of the study, the NOAEL value for repeated dose toxicity of the given test chemical in male and female F344 rats was considered to be 1250 mg/kg/day.
In another study, the given test chemical was assessed for its possible toxic potential. For this purpose, Combined repeated dose and reproduction / developmental screening was performed as per OECD Guideline 422. Male and female Crl:CD (SD) rats were used in the study. The test compound was dissolved in water and used at dose levels of 0, 40, 200 or 1000 mg/Kg/day. The male rats were treated for 42 days and female rats were treated for 41-47 days. Recovery group of 0 and 1000 mg/Kg/day was also included in the study. The treated animals were noted for clinical signs, functional battery observations, body weight, food consumption, urinanalysis, hematology, blood chemistry, organ weight changes and histopathology. No adverse effects were noted in the various parameters studied. Based on the observations made, No Observed Adverse Effect Level (NOAEL) for the given test chemical was considered to be 1000 mg/Kg/day.
Thus based on the above studies, the No Observed Adverse Effect Level (NOAEL) was considered to be 1250 mg/kg body weight/day and hence is not likely to classify for repeated oral toxicity as per the criteria mentioned in CLP regulation.
Repeated dose toxicity: Inhalation
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. Also, the given test chemical has very low vapor pressure 2.493128e-10 Pa, so the potential for the generation of inhalable vapors is very low. The normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for repeated inhalation toxicity was considered for waiver.
Repeated dose toxicity: Dermal
A short-term toxicity study does not need to be conducted because exposure of humans via dermal in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the acute dermal toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. 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 test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that test chemical shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.
Justification for classification or non-classification
Based on the data available and applying the weight of evidence approach, the given test chemical does not exhibit toxic nature upon repeated exposure by oral route of exposure. Hence, it is not likely to classify as toxic as per the criteria mentioned in CLP regulation. For repeated inhalation and repeated dermal toxicity wavier was added so, not possible to classify.
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