title: The bottom-up approach to bounding potential low-dose cancer risks from formaldehyde: An update.
abstract: In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the background cancer risk and the background (endogenous) concentration of a cancer-related exposure biomarker in specific target tissues. After allowing for statistical uncertainty in these two parameters, the ratio of the background risk to background exposure provides a conservative slope factor estimate that can be utilized to bound the added risk that may be associated with incremental exogenous exposures. Our original bottom-up estimates were markedly smaller than those obtained previously by the US Environmental Protection Agency (USEPA) with a conventional top-down approach to modeling nasopharyngeal cancer and leukemia mortality data from a US worker cohort. Herein we provide updated bottom-up estimates of risk for these two cancers that are smaller still, and rely upon more robust estimates of endogenous and exogenous formaldehyde-DNA adducts in monkeys and a more robust estimate of the DNA adduct elimination half-life in rats, both obtained very recently. We also re-examine the worker mortality data used by USEPA in developing its estimate of human leukemia incidence from lifetime exposure to 1 ppm airborne formaldehyde. Finally, we compare a new bottom-up slope estimate of the risk of rat nasal cancer with conventional top-down estimates obtained with empirical dose-response modeling of rat nasal cancer bioassay data.
authors: TBS Associates, 7500 Rainwater Road, Raleigh, NC 27615, USA; Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, 166 Rosenau Hall, CB #7431, Chapel Hill, NC 27599-7431, USA. Electronic address: tbstarr@mindspring.com.
authors: Thomas B
authors: TB
authors: Starr
authors: Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, 166 Rosenau Hall, CB #7431, Chapel Hill, NC 27599-7431, USA. Electronic address: jswenber@email.unc.edu.
authors: James A
authors: JA
authors: Swenberg
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002277:Carcinoma; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005404:Fixatives / Q000493:pharmacokinetics / Q000633:toxicity*; D005557:Formaldehyde / Q000493:pharmacokinetics / Q000633:toxicity*; D000882:Haplorhini; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007938:Leukemia / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015233:Models, Statistical; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D051381:Rats; D018570:Risk Assessment; D013045:Species Specificity; D035501:Uncertainty
chemical_list: D018736:DNA Adducts; D005404:Fixatives; D005557:Formaldehyde
keywords: Bottom-up approach; Carcinogenic risk assessment; Endogenous formaldehyde; Exogenous formaldehyde; Formaldehyde-DNA adducts; Upper 95% confidence bound