title: Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment.
abstract: Formaldehyde is a widely used high production chemical that is also released as a byproduct of combustion, off-gassing of various building products, and as a fixative for pathologists and embalmers. What is not often realized is that formaldehyde is also produced as a normal physiologic chemical in all living cells. In 1980, chronic inhalation of high concentrations of formaldehyde was shown to be carcinogenic, inducing a high incidence of nasal squamous cell carcinomas in rats. Some epidemiologic studies have also found increased numbers of nasopharyngeal carcinoma and leukemia in humans exposed to formaldehyde that resulted in formaldehyde being considered a Known Human Carcinogen. This article reviews the data for rodent and human carcinogenicity, early Mode of Action studies, more recent molecular studies of both endogenous and exogenous DNA adducts, and epigenetic studies. It goes on to demonstrate the power of these research studies to provide critical data to improve our ability to develop science-based cancer risk assessments, instead of default approaches. The complexity of constant physiologic exposure to a known carcinogen requires that new ways of thinking be incorporated into determinations of cancer risk assessment for formaldehyde, other endogenous carcinogens, and the role of background endogenous DNA damage and mutagenesis.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA. jswenber@email.unc.edu
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Moeller
authors.forename: Kun
authors.initials: K
authors.lastname: Lu
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Starr
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D054750:Ecotoxicology; D005557:Formaldehyde / Q000506:poisoning / Q000633:toxicity*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced*; D018570:Risk Assessment
chemical_list: D005557:Formaldehyde