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EC number: 217-752-2 | CAS number: 1948-33-0
- 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 cumulative toxic effects of the test chemical in rats were evaluated in the 13 week study. The test substance was administered in diet to male and female F344/N rats at a dose level of 0, 2500, 5000 or 10000 ppm for 13 weeks after weaning. This dose level is equivalent to a daily dose of approximately 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females. The following parameters were evaluated: body weight and feed consumption, hematology, clinical chemistry and coagulation analysis, sperm motility and vaginal cytology. A complete histopathological examination was conducted. The LOAEL value of 2-tert-butylhydroquinone was found to be 200 mg/kg/day in female rats due to effect on length ofestrous cycles. The NOAEL value in male rats was determined to be 200 mg/kg/day, based on no effects observed during analysis of body weight, feed consumption and sperm parameters. At various time points there were increases in serum bile acid levels and serum alanine aminotransferase activity levels in male and female rats exposed to the test chemical. Such increases are generally associated with liver toxicity and since histopathologic evaluation did not reveal any evidence of liver toxicity, these marginal increases were not considered to be biologically significant. The effects of the test chemical on reproductive parameters in male rats were observed only at dose level of 5000 ppm. Histopathologic changes were observed in rats exposed to 5000 or 10000 ppm the test chemical which included increased incidences of nasal respiratory epithelial hyperplasia, nasal exudate (males only), splenic pigmentation, splenic atrophy of the red pulp (females only), and kidney mineralization (females only).
Repeated dose toxicity: Inhalation
This end point was considered for waiver considering that the vapor pressure of 2-tert-butylhydroquinone (CAS no 1948-33-0) is not high i.e. 0.00112 mm Hg and also in accordance with column 1 of Annex IX, this end point was considered for waiver since the details for acute toxicity by the inhalation route have already been provided as part of the Annex VII requirements of the REACH regulation in section 7.2.2 of this dossier.
Repeated dose toxicity: Dermal
The test chemical was tested at concentrations of 0.1, 1.0 and 5.0%. Groups of five males and five females of black guinea pigs were dosed with the test chemical or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% were slightly to moderately irritating, while 0.1% produced only weak irritant response. No irritant responses to hydrophilic ointment were observed. 0.1% produced depigmentation, while 20% of animals dosed with 1.0% had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% were depigmented at the treatment site at the final evaluation.The study showed that the test chemical causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%. Hence NOAEL was assessed to be 0.1% (1000 mg/kg) and LOAEL was assessed to be 1% (10000 mg/kg).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Male and female F344/N rats were fed diets containing 0, 2500, 5000 or 10000 ppm of the test chemical for 13 weeks after weaning to study the cumulative toxic effects of the substance.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Male and female F344/N rats in the F0 generation were obtained from Taconic Farms (German-town, NY). Offspring (F 1 generation) of the breeders from the perinatal phase of the study.
- Age at study initiation: 34 days
- Housing: Rats were housed five per cage in polycarbonate cages with bedding
- Diet (e.g. ad libitum): NIH-07 open formula mash diet, ad libitum
- Water (e.g. ad libitum): Tap water via automatic watering system; available ad libitum
- Acclimation period: None
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.7°C to 24.2°C
- Humidity (%): 35.8 %-79.3 %
- Air changes (per hr): minimum of 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours/day - Route of administration:
- oral: feed
- Vehicle:
- other: NIH-07 open formula mash diet
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Storage temperature of food: The dose formulations were stored in sealed containers in the dark at 5°C for no longer than 3 weeks. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and stability analyses of the dose formulations were conducted by the analytical chemistry laboratory using high-performance liquid chromatography.
- Duration of treatment / exposure:
- 13 weeks after weaning
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
0, 2500, 5000, or 10000 ppm (0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females)
Basis:
other: Approx 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females - No. of animals per sex per dose:
- Control: 10 males and 10 females
2500 ppm: 10 males and 10 females
5000 ppm: 10 males and 10 females
10000 ppm: 10 males and 10 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: No F1 offspring resulted from F0 females fed diets containing 20000 or 40000 ppm, so these exposure levels were not used in the 13-week rat study
- Rationale for animal assignment: Animals were distributed randomly into groups of approximately equal initial mean body weights - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
Animals were observed twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
Clinical findings were recorded
BODY WEIGHT: Yes
- Time schedule for examinations: The animals were weighed initially, weekly, and at the end of the study
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
Feed consumption was recorded as an average of grams per animal per day.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 13 weeks
- Parameters examined: Hematocrit level, hemoglobin concentration, erythrocyte count, reticulocyte count, nucleated erythrocyte count, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, and leukocyte count and differential.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 13 weeks
- Parameters examined: Blood urea nitrogen, creatinine, total protein, albumin, alkaline phosphatase, creatine kinase, sorbitol dehydrogenase, and bile acids
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
Sperm Motility and Vaginal Cytology Evaluation:
Sperm and vaginal fluid samples were evaluated in all groups at the end of the studies. The parameters evaluated in males were sperm count and motility. The right cauda, right epididymis, and right testis were weighed. Vaginal fluid samples were collected for up to 7 consecutive days prior to the end of the studies for vaginal cytology evaluations. The parameters evaluated in females were relative frequency of estrous stages and estrous cycle length - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organs weighed were the heart, right kidney, liver, lungs, right testis, and thymus
HISTOPATHOLOGY: Yes
Complete histopathologic examinations were performed. In addition to gross lesions, tissue masses, and associated lymph nodes, the tissues examined included: adrenal gland, bone and marrow, brain, clitoral gland, esophagus, heart (with aorta), large intestine (cecum, colon, rectum), kidneys, liver, lungs and main stem bronchi, lymph nodes (mandibular and mesenteric), mammary gland, nasal cavity and turbinates, ovaries, pancreas, parathyroid gland, pituitary gland, preputial gland, prostate gland, salivary gland, skeletal muscle, skin, small intestine (duodenum, jejunum, ileum), spinal cord and sciatic nerve, spleen, stomach (fore stomach and glandular stomach), testis with epididymis and seminal vesicle, thymus, thyroid gland, trachea, urinary bladder, and uterus. - Statistics:
- Williams' or Dunnett' s test (organ and body weights) or Dunn's test (spermatid and epididymal spermatozoal parameters)
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- The final mean body weights of males and females in the 5000 and 10000 ppm groups were significantly lower than those of the controls
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Feed consumption by exposed groups was lower than that by controls at week 2, and, feed consumption by 5000 and 10000 ppm males and 10000 ppm females was slightly lower than that consumed by controls at the end of the study
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- The increases observed in the Serum bile acid levels and Serum alanine aminotransferase activity were marginal, and as histopathologic evaluation did not reveal evidence of liver toxicity, these increases were not considered to be biologically significant
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The organ weight differences were associated with histopathologic lesions and in many cases were secondary to lower body weights of exposed groups. Therefore, they were not considered clearly related to t-butylhydroquinone exposure
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased incidences of splenic pigmentation were observed in males and females exposed to 5000 or 10000 ppm, and incidences of atrophy of the red pulp were observed in these groups of females
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Details on results:
- The mean spermatid count, spermatid heads per testis, and spermatid heads per gram of testis were significantly decreased in males exposed to 5000 ppm. The estrous cycles of females exposed to 2500 or 5000 ppm were significantly longer than that of the controls. There were no biologically significant changes in clinical pathology parameters or in organ weights.
- Dose descriptor:
- LOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Significantly longer estrous cycles
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Body weight, feed consumption, sperm analysis
- Critical effects observed:
- not specified
- Conclusions:
- The LOAEL value of the test chemical when administered in diet was found to be 200 mg/kg/day in female rats, as significantly longer estrous cycles were observed at this dose as compared to controls. The NOAEL value in male rats was determined to be 200 mg/kg/day, based on no effects observed during analysis of body weight, feed consumption and sperm parameters.
- Executive summary:
The cumulative toxic effects of the test chemical in rats were evaluated in the 13 week study. The test substance was administered in diet to male and female F344/N rats at a dose level of 0, 2500, 5000 or 10000 ppm for 13 weeks after weaning. This dose level is equivalent to a daily dose of approximately 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females.
The following parameters were evaluated: body weight and feed consumption, hematology, clinical chemistry and coagulation analysis, sperm motility and vaginal cytology. A complete histopathological examination was conducted. The LOAEL value of 2-tert-butylhydroquinone was found to be 200 mg/kg/day in female rats due to effect on length ofestrous cycles. The NOAEL value in male rats was determined to be 200 mg/kg/day,based on no effects observed during analysis of body weight, feed consumption and sperm parameters.
At various time points there were increases in serum bile acid levels and serum alanine aminotransferase activity levels in male and female rats exposed to the test chemical. Such increases are generally associated with liver toxicity and since histopathologic evaluation did not reveal any evidence of liver toxicity, these marginal increases were not considered to be biologically significant. The effect of the test chemical on reproductive parameters in male rats were observed only at dose level of 5000 ppm. Histopathologic changes were observed in rats exposed to 5000 or 10000 ppm the test chemical which included increased incidences of nasal respiratory epithelial hyperplasia, nasal exudate (males only), splenic pigmentation, splenic atrophy of the red pulp (females only), and kidney mineralization (females only).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- K2 level data; Male rat data
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- 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:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data is from secondary literature
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Effect of the test chemical was studied using guinea pigs
- GLP compliance:
- no
- Species:
- guinea pig
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Outbred black guinea pigs were used
- Type of coverage:
- not specified
- Vehicle:
- other: hydrophilic ointment
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
0.1, 1.0, and 5.0% in 1 ml
Basis:
no data - No. of animals per sex per dose:
- 5/sex/group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
Groups of five males and five females were dosed with 2-tert-butylhydroquinone or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints- Positive control:
- No data
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- No data
- Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- not specified
- Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- At 0.1% the test chemical produced weak irritant responses and did not produced depigmentation and at 1.0%, 20% of animals had spotty or uniform loss of pigment
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Based on:
- dissolved
- Sex:
- male/female
- Basis for effect level:
- other: At 0.1%, the test substance produced weak irritant responses and did not produce depigmentation.
- Dose descriptor:
- LOAEL
- Effect level:
- 10 000 mg/kg bw/day
- Based on:
- dissolved
- Sex:
- male/female
- Basis for effect level:
- other: At 1.0%, 20% of animals had spotty or uniform loss of pigment.
- Critical effects observed:
- not specified
- Conclusions:
- Based on the effects observed in the study at 0.1%, the test chemical produced weak irritant responses and did not produced depigmentation and at 1.0%, 20% of animals had spotty or uniform loss of pigment. The NOAEL and LOAEL was assessed to be 0.1% (1000 mg/kg) and 1% (10000 mg/kg) respectively.
- Executive summary:
The test chemical was tested at concentrations of 0.1, 1.0 and 5.0%. Groups of five males and five females of black guinea pigs were dosed with the test chemical or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% were slightly to moderately irritating, while 0.1% produced only weak irritant response. No irritant responses to hydrophilic ointment were observed.
0.1% produced depigmentation, while 20% of animals dosed with 1.0% had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% were depigmented at the treatment site at the final evaluation.The study showed that the test chemical causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%. Hence NOAEL was assessed to be 0.1% (1000 mg/kg) and LOAEL was assessed to be 1% (10000 mg/kg).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- chronic
- Species:
- guinea pig
- Quality of whole database:
- Data is from secondary source
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Data available for the target chemical was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:
Repeated dose toxicity: Oral
The cumulative toxic effects of the test chemical in rats were evaluated in the 13 week study. The test substance was administered in diet to male and female F344/N rats at a dose level of 0, 2500, 5000 or 10000 ppm for 13 weeks after weaning. This dose level is equivalent to a daily dose of approximately 0, 200, 400 or 800 mg/kg bw for males and 0, 200, 400 or 750 mg/kg bw for females. The following parameters were evaluated: body weight and feed consumption, hematology, clinical chemistry and coagulation analysis, sperm motility and vaginal cytology. A complete histopathological examination was conducted. The LOAEL value of 2-tert-butylhydroquinone was found to be 200 mg/kg/day in female rats due to effect on length ofestrous cycles. The NOAEL value in male rats was determined to be 200 mg/kg/day, based on no effects observed during analysis of body weight, feed consumption and sperm parameters. At various time points there were increases in serum bile acid levels and serum alanine aminotransferase activity levels in male and female rats exposed to the test chemical. Such increases are generally associated with liver toxicity and since histopathologic evaluation did not reveal any evidence of liver toxicity, these marginal increases were not considered to be biologically significant. The effects of the test chemical on reproductive parameters in male rats were observed only at dose level of 5000 ppm. Histopathologic changes were observed in rats exposed to 5000 or 10000 ppm the test chemical which included increased incidences of nasal respiratory epithelial hyperplasia, nasal exudate (males only), splenic pigmentation, splenic atrophy of the red pulp (females only), and kidney mineralization (females only).
The cumulative toxic effects of the test chemical in mice were evaluated in the 13 week study. The test substance was administered in diet to male and female B6C3F1 mice at a dose level of 0, 2500, 5000, 10000, 20000 or 40000 ppm for 13 weeks. These dose levels are equivalent to a daily dose of approximately 0, 440, 880, 1950, 4000 or 8400 mg/kg bw for males and 0, 500, 1100, 2200, 4600 or 9000 mg/kg bw for females. The following parameters were evaluated: body weight and feed consumption, hematology, clinical chemistry and coagulation analysis, sperm motility and vaginal cytology. A complete histopathological examination was conducted. The NOAEL value of the test chemical when administered in diet was found to be 880 mg/kg/day in male mice, whereas it was determined to be 1100 mg/kg/day in female mice,based on no effects observed on any parameter during analysis at these dose levels. Following effects were observed at higher dose levels: Final mean body weights and body weight gains of male and female mice in the 10000, 20000, and 40000 ppm groups were significantly lower than those of the control groups. Increase in segmented neutrophil counts at doses above 10000 ppm was the only clinical pathology change attributed to chemical exposure. There were no biologically significant differences in organ weights other than Ieft caudal, left epididymis, and left testis weights of males exposed to 10000 or 40000 ppm which were significantly lower. The estrous cycle of females exposed to 40000 ppm was significantly longer than that of the controls. Increased incidences of mucosal hyperplasia were observed in the forestomach of male mice exposed to 20000 or 40000 ppm and in female mice exposed to 10000, 20000, or 40000. The severity of this lesion also increased with increasing exposure concentration. Increased incidences of inflammation occurred in the nose and skin of males and females exposed to 10000, 20000 or 40000 ppm.
The safety of the test chemical as an oil-soluble food grade antioxidant was evaluated in another rat chronic toxicity test. A diet containing 0%, 0.016%, 0.05%, 0.16% or 0.5 % (approx.0, 8, 25, 80 or 250 mg/kg bw) of the test chemical was fed to groups of 55 male and 55 female Sprague-Dawley rats for 20 months. The following parameters were assessed: behavior, growth rate, feed intake, diet efficiency, mortality, organ weight, hematology, clinical chemistry,urinalyses, gross and histopathological observations. Measurements of these parameters in the treated groups gave results which were similar to the controls. A NOAEL value for the test chemical of approximately 250 mg/kg bw was determined in the study. At this dose level, a slight decrease in brain weight was observed in male rats which was not associated with any pathology or behavioral change.
The safety of the test chemical as an oil-soluble food grade antioxidant was evaluated in a 2 year chronic toxicity test in dogs. A diet containing 0%, 0.05%, 0.158% or 0.5 % (approx.0,12.5, 39.5or125 mg/kg bw) of the test chemical was fed to groups of 4 male and 4 female beagle dogs for 2 years. The following parameters were assessed:organ weight, hematology, clinical chemistry, urinalyses, gross and histopathological observations. Measurements of these parameters in the treated groups yielded results that were similar to the controls. A NOAEL value of approximately 125 mg/kg bw was determined for the test chemical.
Repeated dose toxicity: Inhalation
This end point was considered for waiver considering that the vapor pressure of 2-tert-butylhydroquinone (CAS no 1948-33-0) is not high i.e. 0.00112 mm Hg and also in accordance with column 1 of Annex IX, this end point was considered for waiver since the details for acute toxicity by the inhalation route have already been provided as part of the Annex VII requirements of the REACH regulation in section 7.2.2 of this dossier.
Repeated dose toxicity: Dermal
The test chemical was tested at concentrations of 0.1, 1.0 and 5.0%. Groups of five males and five females of black guinea pigs were dosed with the test chemical or the vehicle (hydrophilic ointment) daily (M-F) for 13 weeks. The application site was evaluated weekly for degree of pigmentation loss and irritation. Twenty-four hours after final application, sites were evaluated for depigmentation, irritation and hyperpigmentation. Subsequently, the application site was depilated and re-evaluated for the same endpoints. Repetitive exposure to concentrations of 1.0% and 5.0% were slightly to moderately irritating, while 0.1% produced only weak irritant response. No irritant responses to hydrophilic ointment were observed. 0.1% produced depigmentation, while 20% of animals dosed with 1.0% had spotty or uniform loss of pigment at the site of treatment. Approximately 40% of animals dosed with 5% were depigmented at the treatment site at the final evaluation.The study showed that the test chemical causes depigmentation in black guinea pigs at concentrations of 1% or greater, but that a no-effect threshold for this endpoint exists at a concentration between 0.1 and 1.0%. Hence NOAEL was assessed to be 0.1% (1000 mg/kg) and LOAEL was assessed to be 1% (10000 mg/kg).
Repeated dose dermal toxicity study was also performed to determine the toxic nature of the test chemical upon repeated exposure by dermal route. The study was performed on male volunteer. The positive reaction observed with the test chemical in 1% (equivalent to 10000 mg/kg bw/d) alcohol. When the patient changed his job and exposure to the cutting fluid ceased the dermatitis quickly healed. Based on the observations made, the low observed adverse effect level (LOAEL) for the test chemical is considered to be 10000 mg/Kg/day.
Based on the data available for the target chemical, the test chemical is not likely to be toxic upon repeated exposure by oral, dermal and inhalation route of exposure.
Justification for classification or non-classification
The substance is unlikely to show repeated dose toxicity effect for oral,dermal and inhalation route and thus will not be considered for further classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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