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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No studies on toxicokinetics of 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (DBMC) are available. However, considering the toxicokinetic profile of structural analogues and taking into account the experiences with DBMC in acute and repeated dose toxicity studies, a characterization of DBMC toxicokinetics can be conducted.

DBMC is a solid powder with a low vapour pressure (calculated to be < 0.1hPa, 20°C) under normal ambient conditions, therefore inhalation exposure to the vapour might be negligible.

DBMC is practically insoluble in water (0.007 mg/l at 20°C). However, the molecular mass of 342 g/mol and the n-octanol/water coefficient (log Pow of 6.25) suggest intestinal absorption subsequent to oral ingestion. This assumption is confirmed by data from acute oral toxicity studies and repeated dose toxicity studies. However, acute toxicity is low because LD50 values are high (greater than or even to 5000 mg/kg bw, Takagi 1994, American Cyanamid Company 1965, Hagan 1952, Garlanda 1962, Stasenkova 1977. In addition, studies with repeated oral dosing of rats indicating bioavailability of the compound by showing dose related toxic effects at doses > 12.7 mg/kg bw, predominantly in the testes and liver. Available repeated dose toxicity studies are a subacute toxicity study with rats (MHWJ 1996), subchronic toxicity studies with rats (Bayer AG 1982, Takagi 1994) or dogs (American Cyanamid Company 1965), a chronic feeding study with rats (Takagi 1994) and a reproduction toxicity screening study (MHWJ 1999). The determined NOAELs in these studies were in the order of 10 mg/kg bw/day.

DBMC showed a very low skin and eye irritating potential in rabbits (Raschig AG 1995). In addition, in a modified Local Lymph node Assay (LLNA) neither a non-specific (irritant) nor a specific immune stimulating (sensitizing) potential of the test substance was indicated in NMRI mice (Bayer Schering Pharma AG 2010). Furthermore, the dermal LD50 value of > 10000 mg/kg and the absence of significant signs of systemic toxicity when dosed once at 10000 mg/kg bw reveal a very low toxic potential of DMBC after dermal exposure.

The formation of DNA reactive metabolites is unlikely, since in vitro and in vivo mutagenicity tests (Ames assay MHWJ 1996, in vitro chromosome aberration assay MHWJ 1996, in vivo micronucleus assay OECD SIDS 2003) show negative results. In addition, the cytotoxicity of the test substance DMBC was reduced in the presence of the rat liver microsomal fraction. This suggests that detoxification of DBMC occurs as a result of liver enzyme activity or even as a detoxification by non-specific protein-binding.