Registration Dossier
Registration Dossier
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EC number: 204-327-1 | CAS number: 119-47-1
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- other: Assessment of toxicokinetic behaviour
- Adequacy of study:
- supporting study
- Reliability:
- other: Assessment of toxicokinetic behaviour
- Rationale for reliability incl. deficiencies:
- other: other: Assessment of toxicokinetic behaviour
Data source
Reference
- Reference Type:
- other: summary
- Title:
- Assessment of toxicokinetic behavviour
- Author:
- Krueger I.
- Year:
- 2 010
- Bibliographic source:
- Assessment of toxicokinetic behavviour
Materials and methods
- Principles of method if other than guideline:
- other: Assessment of toxicokinetic behaviour
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol
- EC Number:
- 204-327-1
- EC Name:
- 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol
- Cas Number:
- 119-47-1
- Molecular formula:
- C23H32O2
- IUPAC Name:
- 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5-methylphenyl)methyl]-4-methylphenol
- Details on test material:
- other: Assessment of toxicokinetic behaviour
Constituent 1
Test animals
- Species:
- other: Assessment of toxicokinetic behaviour
Administration / exposure
- Route of administration:
- other: Assessment of toxicokinetic behaviour
- Vehicle:
- other: Assessment of toxicokinetic behaviour
- Duration and frequency of treatment / exposure:
- Assessment of toxicokinetic behaviour
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Assessment of toxicokinetic behaviour
- No. of animals per sex per dose / concentration:
- Assessment of toxicokinetic behaviour
Results and discussion
- Preliminary studies:
- Assessment of toxicokinetic behaviour
Any other information on results incl. tables
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 below 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 g/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, Hagan 1952, Garlanda 1962, Stasenkova 1977, Sumitomo Chemical 1977, Takaki 1994, EPA 1992 Monsanto study); systemic availability was indicated by clinical signs like hypoactivity and ataxia at doses = 2500 mg/kg bw (EPA 1992 Monsanto study). 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 irritating potential in humans (Kimmerle 1958, American Cyanamid Company 1959) and rabbits (EPA 1992 Monsanto study). In addition, Vulkanox BKF had a very low skin sensitization potential in humans (American Cyanamid Company 1959). Furthermore, the dermal LD50 of above 2000 mg/kg and the absence of significant signs of systemic toxicity when dosed once at 2000 mg/kg bw (EPA 1992 Monsanto study) reveal a low toxic potential of DBMC after dermal exposure.
The formation of DNA reactive metabolites in unlikely, since in vitro and in vivo mutagenicity tests (Ames assay MHWJ 1996, RCC 1986a, in vitro chromosome aberration assay MHWJ 1996, in vivo micronucleus assay RCC 1986b ) show negative results. In addition, the cytotoxicity of the test substance DBMC 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.
Applicant's summary and conclusion
- Executive summary:
Assessment of toxicokinetic behaviour
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