Formaldehyde mechanistic data and risk assessment: Endogenous protection from DNA adduct formation

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Abstract

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.

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    This manuscript was developed for the International Expert Panel on Carcinogen Risk Assessment and under the aegis of the Environmental Health and Safety Council of the American Health Foundation. The membership of the Panel is provided in the first paper of the series.

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