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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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
Reference
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).

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
Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
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
Reference
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).

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.