title: Development of a cancer-based chronic inhalation reference value for hexavalent chromium based on a nonlinear-threshold carcinogenic assessment.
abstract: The carcinogenicity of hexavalent chromium(CrVI) is of significant interest to regulatory agencies for the protection of public health and to industry. Additionally, the mode of action (MOA) and conditions under which CrVI may induce carcinogenicity (e.g., reductive capacity considerations) have recently been the subject of significant scientific debate. Epidemiological data supported by data relevant to the carcinogenic MOA support considering nonlinear-threshold carcinogenic assessments for comparison to default linear low-dose extrapolation approaches. This study reviews epidemiological studies available in the scientific literature and conducts additional statistical dose-response analyses to identify potential carcinogenic thresholds and points of departure (PODs) in the context of supportive MOA information for a nonlinear-threshold inhalation carcinogenic assessment. Dosimetric adjustments and application of appropriate uncertainty factors (total UF of 30) to the selected cumulative exposure POD results in a cancer-based chronic inhalation reference value (ReV) of 0.24 μgCrVI/m(3). This chronic ReV is 300 times higher than the 1 in 100,000 excess cancer risk air concentration of 8E-04 μg/m(3) based on USEPA's unit risk factor.
authors.affiliation: Texas Commission on Environmental Quality (TCEQ), Toxicology Division, Austin, TX 78711-3087, USA. Joseph.Haney@tceq.texas.gov
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Haney
authors.forename: Neeraja
authors.initials: N
authors.lastname: Erraguntla
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sielken
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Valdez-Flores
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000633:toxicity*; D002857:Chromium / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000139:chemically induced*; D012016:Reference Values; D018570:Risk Assessment / Q000379:methods
chemical_list: D002274:Carcinogens, Environmental; D002857:Chromium; C074702:chromium hexavalent ion