Authors: Leng, Jiapeng, Chih-Wei Liu, Hadley J. Hartwell, Rui Yu, Yongquan Lai, Wanda M. Bodnar, Kun Lu, and James A. Swenberg.
In this study, both exogenous and endogenous DNA mono-adduct (N2-HOMe-dG) and DNA–protein crosslinks (dG-Me-Cys) were measured to assess the formation of DNA adducts arising from the inhalation to 1, 30, 300 ppb [13CD2]-formaldehyde in rats for 28 days using ultrasensitive nano liquid chromatography–tandem mass spectrometry. Endogenous formaldehyde-induced DNA mono-adducts and DPCs were measured in all tissues examined and the levels of endogenous adducts were not altered by the exposure of exogenous isotope labeled formaldehyde. Exogenous formaldehyde-induced DNA mono-adducts and DPCs were undetectable in all tissues examined. These novel findings substantiate the threshold mode of action of carcinogenesis of formaldehyde and further improve risk assessment of low formaldehyde exposures in the range of regulatory limit values such as the WHO indoor guidance value of 0.1 mg/m³ (≈ 0.08 ppm) and the EU SCOEL recommendation for workplace exposures of 0.3 ppm.