2-tert-butyl-4-methoxyphenol

Carcinogenicity

Description of key information

Carcinogenicity Study:

In a carcinogenic study, the effect of the test chemical was investigated. Male Syrian golden hamsters were given a pellet diet containing 2.0% of the test chemical or a powdered diet containing 1.0% of the test chemical for 24 weeks. Control animal were given plain diet for 24 weeks. Polyploid tumors and papillomas in the forestomach were induced in all hamsters given either of the two diets. Long finger-like processes of squamous cell epithelium showing papillomatosis were also observed as well as downward growth into the submucosa in some areas of the tumors. The results strongly suggest that the test chemical is carcinogenic in the Syrian golden hamster. Therefore, LOAEL was considered to be 1% of the test chemical when male Syrian golden hamsters are exposed to the test chemical in diet for 24 weeks.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

1 000 mg/kg bw/day

Study duration:

chronic

Species:

hamster, Syrian

Quality of whole database:

The data is from a Klimisch 2 data source.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the positive results of carcinogenicity of the test chemical, it is concluded that the test chemical is classified as Carc 2 category as per the CLP regulation.

Additional information

Carcinogenicity Study 1:

In a carcinogenic study, the effect of the test chemical was investigated. Male Syrian golden hamsters were given a pellet diet containing 2.0% of the test chemical or a powdered diet containing 1.0% of the test chemical for 24 weeks. Control animal were given plain diet for 24 weeks. Polyploid tumors and papillomas in the forestomach were induced in all hamsters given either of the two diets. Long finger-like processes of squamous cell epithelium showing papillomatosis were also observed as well as downward growth into the submucosa in some areas of the tumors. The results strongly suggest that the test chemical is carcinogenic in the Syrian golden hamster. Therefore, LOAEL was considered to be 1% of the test chemical when male Syrian golden hamsters are exposed to the test chemical in diet for 24 weeks.

Carcinogenicity Study 2:

In a carcinogenic study, the effect of the test chemical or crude test chemical were investigated. Male Syrian golden hamsters were given a diet containing 1.0% of the test chemical or crude test chemical for 1 to 4 weeks. Control animal were given plain diet for 1 to 4 weeks. When induced hyperplasia was compared in the hamsters given 2-tert-test chemical, 3-tert-test chemical or crude test chemical, 3-tert test chemical and crude test chemical induced the most severe hyperplasia. Hence, hyperplasia induced in the hamsters given crude test chemical may be due to the high presence of 3-tert-test chemical in crude test chemical. Based on these observations, it is considered likely that the 3-tert isomer is responsible for the tumorigenicity of crude test chemical on the forestomach of Syrian golden hamsters. Since 2-tert-test chemical is regarded to be less potent in inducing hyperplasia it might be preferable to crude test chemical, which is mainly composed of 3-tert-test chemical, as an antioxidant in food. Therefore, LOAEL was considered to be 1% of 2-tert-test chemical, 3-tert-test chemical or crude test chemical when male Syrian golden hamsters are exposed to the test chemical in diet for 1-4 weeks.

Carcinogenicity Study 3:

In a carcinogenic study, the effect of the test chemical was investigated. Male and female Fischer 344 rats were exposed to the test chemical by diet for 104 weeks. The test chemical was mixed in diet at the concentrations of 0, 0.5 or 2%. The results shows that the test chemical fed at levels of 0.5% or 2% increased the incidence of hyperplasia of the forestomach in a dose-dependent manner. There were also a significant decrease in brain weight in treated males, and increases in the relative weights of salivary glands and hearts in females. Feeding of the test chemical in the diet caused superficial necrosis, ulceration and hyperplasia of the squarnous epithelium of the forestomach. The first tumour, a pituitary-gland tumour in a female in the 0.5% dose group, occurred at 41 weeks. In the 2% dose group, there were significantly increased incidences of papillomas of the forestomach in males and females. An occurrence of squamous-cell carcinomas of the forestomach was also seen in males and females, while the first carcinoma appear at week 59 in males and at week 82 in females. No such increase in tumour incidence was observed in 0.5% dose rats of either sex.Therefore, LOAEL was considered to be 0.5% of the test chemical when male and female Fischer 344 rats were exposed to the test chemical by diet for 104 weeks prior to eight weeks of recovery with plain diet.

Carcinogenicity Study 4:

In 15 month repeated dose toxicity study, the effect of the test chemical was evaluated in Fischer 334  male rats. The test chemical was administered by oral feeding in the concentration of 0 and 1000 mg/kg/day (0 and 2 %) of the test chemical. The results showed that the test chemicals was toxic. Significent toxic changes were observed in histopathology of forestomch in 12 months treated rats seen with squamous-cell carcinoma. Several rats had cauliflower-like papillary growths projecting from the epithelium. These papillary growths showed a high rate of proliferation of the covering squamous epithelium. Similar histopathological changes werealso observed in 15 months study. Hence, LOAEL was considered to be 0 and 1000 mg/kg/day (0 and 2 %) when Fischer 334  male rats were exposed daily to the test chemical by oral route for 15 months.

Justification for selection of carcinogenicity via oral route endpoint:

The LOAEL value of the test chemical in Syrian golden  was found at a dose level of 1% (1000 mg/kg diet).