Endogenous versus Exogenous DNA Adducts: Their Role in Carcinogenesis, Epidemiology, and Risk Assessment

There is a strong need for science-based risk assessment that utilizes known data from diverse sources to arrive at accurate assessments of human health risk. Such assessments will protect the public health without mandating unreasonable regulation. This paper utilizes 30 years of research on three "known human carcinogens": formaldehyde, vinyl chloride (VC), and ethylene oxide (EO), each of which forms DNA adducts identical to endogenous DNA adducts in all individuals. It outlines quantitative data on endogenous adducts, mutagenicity, and relationships between endogenous and exogenous adducts. Formaldehyde has the richest data set, with quantitative data on endogenous and exogenous DNA adducts from the same samples. The review elaborates on how such data can be used to inform the current risk assessment on formaldehyde, including both the biological plausibility and accuracy of projected risks. Finally, it extends the thought process to VC, EO, and additional areas of potential research, pointing out needs, nuances, and potential paths forward to improved understanding that will lead to strong science-based risk assessment.