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IN VITRO

In a reverse gene mutation assay in bacteria (Hüls AG, 1987), strains TA1535, TA1537, TA1538, TA98 and TA100 of S. typhimurium were exposed to p-tert.-Butyltoluene (purity not given) in DMSO at concentrations of 10-5000 µg/plate in the presence and absence of mammalian metabolic activation (standard plate test and preincubation test). The study was conducted in accordance with OECD TG 471.

p-tert.-Butyltoluene was tested up to cytotoxic concentrations. The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence of induced mutant colonies over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

The results of this key study are confirmed by other mutagenicity tests.

In a reverse gene mutation assay in bacteria (Dean et al, 1985), strains TA98, TA100, TA1535, TA1537 and TA1538 of S. typhimurium and strains WP2 and WP2 uvrA of E. coli were exposed to p-tert-butyltoluene (purity 96%) in DMSO and hexane at concentrations of 0.2, 2, 20, 50 and 2000 µg/plate in the presence and absence of mammalian metabolic activation (preincubation test).

No information is given on cytotoxicity. The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence of induced mutant colonies over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data, with exception of the data on cytotoxicity lacking in the publication.

In another reverse gene mutation assay in bacteria (Zeiger et al, 1987), strains TA98, TA100, TA1535 and TA1537 of S. typhimurium were exposed to p-tert-butyltoluene (purity 98%) in DMSO at concentrations of 0.3, 1, 3.3, 10, 33, 100, 333, 1000 µg/plate in the presence and absence of mammalian metabolic activation (preincubation test).

p-tert-butyltoluene) was tested up to cytotoxic concentrations. The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence of induced mutant colonies over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

In a rather poorly documented, mammalian cell cytogenetic assay (Chromosome aberration) (Dean et al, 1985), RL4 rat liver epithelial cell cultures were exposed to p-tert-butyltoluene (purity 96%) at concentrations of equivalent to 0.5, 0.25 and 0.125- fold of IC50 (concentration inhibiting cell growth by 50%, not further stated) without metabolic activation.

p-tert-Butyltoluene was tested up to cytotoxic concentration.

There was no evidence of chromosome aberration induced over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 473 for in vitro cytogenetic mutagenicity data, with exception of the documentation deficiencies in the publication.

IN VIVO

No data are available on genotoxicity of p-tert-butyltoluene in experimental animals.

 

p-tert.Butylbenzoic acid, an analogous compound and metabolite of p-tert-butyltoluene in rats, did not induce chromosomal aberrations in rats after oral administration (BG Chemie, 2000).

In this cytogenetic assay (BG Chemie, 2000) Wistar rats (groups of 6/sex) were treated orally with p-tert.butylbenzoic acid (99.8% pure) at doses of 0, 300, 600 mg/kg bw (single dosing). Bone marrow cells were harvested at 24 and 48 hours post-treatment. The vehicle was corn oil. The study was conducted in accordance with OECD TG 475 and GLP guidelines.

Two high dose males died. A weak reduction (females only) of the mitotic indices after treatment with the test item was observed at preparation interval 24 hours indicating a cytotoxic effectiveness of the test item. No statistically significant increase in the frequency of aberrant cells occurred after treatment with the test item as compared to the vehicle control.

Tert.butylbenzoic acid was tested at an adequate dose. The positive control induced the appropriate response.

There was not a significant increase in the frequency of chromosomal aberrations in bone marrow cells after any treatment time.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 475 for in vivo cytogenetic mutagenicity data.


Short description of key information:
IN VITRO
Not mutagenic in bacteria.
Not clastogenic in rat liver cells.

IN VIVO
No data are available.

Endpoint Conclusion:

Justification for classification or non-classification

There is no need to classify 4-tert.-butyltoluene for mutagenicity according to the Directive 67/548/EC or GHS criteria.