Ring-oxidized metabolites of styrene contribute to styrene-induced Clara-cell toxicity in mice.
J Toxicol Environ Health A
; 68(3): 229-37, 2005 Feb 13.
Article
em En
| MEDLINE
| ID: mdl-15762181
ABSTRACT
Styrene produced cytotoxicity in the terminal bronchioles of mice, but not rats, due to metabolites produced in situ by CYP2F2 metabolism. It has generally been presumed that styrene toxicity is mediated by styrene 7,8-oxide, but styrene oxide is not much more toxic than styrene. In contrast, ring-oxidized metabolites (4-vinylphenol or its metabolites) induce much greater toxicity. Administration of 4-vinylphenol results in pneumotoxicity, based on analysis of bronchoalveolar lavage fluid (BALF) at a 5- to 10 fold lower dose than does styrene oxide. In the current research, studies demonstrated that ip administration of 4-vinylphenol for 14 consecutive days at dosages of 6, 20, or 60 mg/kg/d (split into 3 doses) produced cytotoxicity in the terminal bronchioles of mice, but not rats. While higher doses of 4-vinylphenol produced adverse effects in both liver and lung, no liver toxicity was seen in mice exposed to 60 mg/kg/d for 14 d. Approximately 4 d was required for BALF parameters to return to normal following a single administration of 4-vinylphenol. These studies add further support for the role of ring-oxidized metabolites in the pneumotoxicity induced by styrene in mice and the lack thereof in rats.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Estireno
/
Mucosa Respiratória
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article