Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation.
Exposures of rodents to airborne formaldehyde (FA) produce dose-related toxicity, enhanced cell proliferation and squamous cell carcinomas in the nasal passages. The mechanism of FA-induced tumor formation involves DNA-protein crosslink formation and enhanced cell proliferation secondarily to cytotoxicity. The mucociliary apparatus and glutathione protect against low-dose FA-induced effects. Consequently, the mechanistic information is consistent with a very sublinear dose-response curve for tumor formation. The sublinear dose-response of nasal DNA-protein crosslinks levels in rodents and monkeys has been used in the risk assessment of FA.
Conaway
C C
CC
Toxicology and Risk Assessment Program, American Health Foundation, Valhalla, NY 10595-1599, USA.
Whysner
J
J
Verna
L K
LK
Williams
G M
GM
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000096:biosynthesis*; D005557:Formaldehyde / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D018570:Risk Assessment
D002273:Carcinogens; D018736:DNA Adducts; D005557:Formaldehyde; D004247:DNA