title: The impact of recent advances in research on arsenic cancer risk assessment.
abstract: Scientific debate surrounds the regulatory approach for evaluating carcinogenic risk of arsenic compounds. The arsenic ambient water quality criteria (AWQC), based on the assumption of a linear mode of action for skin cancer risk, results in an allowable limit of 0.018ppb in ambient waters; the drinking water Maximum Contaminant Level (MCL) was determined using a similar linear approach. Integration of results from recent studies investigating arsenic's mode of action provide the basis for a change in the approach for conducting an arsenic cancer risk assessment. Results provide support for a concentration demonstrating a dose-dependent transition in response from those representing adaptive changes to those that may be key events in the development of cancer endpoints. While additional information is needed, integration of current research results provides insight for a new quantitative cancer risk assessment methodology as an alternative toxicologically-based dose response (BBDR) cancer modeling. Integration of the new experimental results, combined with epidemiological evidence, support a dose-dependent transition concentration of approximately 0.1μM arsenic. Some uncertainties remain; additional information from chronic in vitro studies underway is needed. Results to date also provide initial insight into variability in population response at low arsenic exposures.
authors.affiliation: ENVIRON International, 1900 N. 18th St., Monroe, LA 71201, USA. Electronic address: rgentry@environcorp.com.
authors.forename: P Robinan
authors.initials: PR
authors.lastname: Gentry
authors.affiliation: The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: HClewell@thehamner.org.
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Clewell
authors.affiliation: ENVIRON International, 1900 N. 18th St., Monroe, LA 71201, USA. Electronic address: tgreene@environcorp.com.
authors.forename: Tracy B
authors.initials: TB
authors.lastname: Greene
authors.affiliation: ENVIRON International, 1900 N. 18th St., Monroe, LA 71201, USA. Electronic address: afranzen@environcorp.com.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Franzen
authors.affiliation: University of New Mexico, Albuquerque, NM 87131-00001, USA; ENVIRON International, 2200 Powell Street, Emeryville, CA 94608. Electronic address: JWYAGER@salud.unm.edu.
authors.forename: Janice W
authors.initials: JW
authors.lastname: Yager
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001152:Arsenicals / Q000009:adverse effects*; D002273:Carcinogens / Q000633:toxicity*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000209:etiology*; D018570:Risk Assessment; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014881:Water Supply / Q000032:analysis
chemical_list: D001152:Arsenicals; D002273:Carcinogens; D014874:Water Pollutants, Chemical; D001151:Arsenic
keywords: Adaptive; Arsenic; Cancer risk; Dose–response; Non-linear