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A Kinetic Analysis of DNA-Deoxy Guanine Adducts in the Nasal Epithelium Produced by Inhaled Formaldehyde in Rats—Assessing Contributions to Adduct Production From Both Endogenous and Exogenous Sources of Formaldehyde.

Authors: Campbell Jr, Jerry L., P. Robinan Gentry, Harvey J. Clewell III, and Melvin E. Andersen.

Goal here of this work was to adapt the pharmacokinetic (PK) model for formaldehyde PKs developed for 14C-DNA-protein crosslinks (DPX) and describe the production of both endogenous and exogenous formaldehyde-DNA reaction products (eg, adducts) for a diverse suite of studies at inhaled concentrations from 0.001 to 15 ppm. Another contribution of the modeling was to assess whether descriptions with a single well-mixed cellular formaldehyde compartment could describe adduct formation from formaldehyde produced both by endogenous cellular metabolism and delivered exogenously by inhalation. This refined PK model for endogenous and exogenous formaldehyde acetal adducts will assist in updating biologically based dose-response models for formaldehyde carcinogenicity.