title: Derivation of inhalation toxicity reference values for propylene oxide using mode of action analysis: example of a threshold carcinogen.
abstract: Propylene oxide (PO) is an important industrial chemical used primarily in the synthesis of other compounds. Inhalation carcinogenesis studies in rodents, with no-observed-adverse-effect levels (NOAELs) of 100 and 200 ppm, have revealed that chronic, high exposure to PO can induce tumors at the site of contact. Despite these characteristics, there is no evidence that typical environmental or occupational exposures to PO constitute a health risk for humans. The nongenotoxic effects of PO (glutathione depletion and cell proliferation) that augment its DNA-reactive and non-DNA-reactive genotoxicity are expected to be similar in humans and rodents. Available evidence on mode-of-action suggests that cancer induction by PO at the site of contact in rodents is characterized by a practical threshold. Human toxicity reference values for potential carcinogenic effects of PO were derived based on nasal tumors identified in rodent studies and specified uncertainty factors. The 95% lower confidence limit on the dose producing a 10% increase in additional tumor risk (LED10) was calculated using the rat and mouse data sets. The human reference values derived from the rat and mouse LED10 values were 0.7 and 0.5 ppm PO, respectively. A similar noncancer reference value, 0.4 ppm, was derived on the basis of non-neoplastic nasal effects in rats.
authors: The Sapphire Group, Inc., 2661 Commons Blvd., Second Floor, Dayton, OH 45431, USA. LMS29@case.edu
authors: Lisa M
authors: LM
authors: Sweeney
authors: Christopher R
authors: CR
authors: Kirman
authors: Richard J
authors: RJ
authors: Albertini
authors: Yu-Mei
authors: YM
authors: Tan
authors: Harvey J
authors: HJ
authors: Clewell
authors: Johannes G
authors: JG
authors: Filser
authors: György
authors: G
authors: Csanády
authors: Lynn H
authors: LH
authors: Pottenger
authors: Marcy I
authors: MI
authors: Banton
authors: Cynthia J
authors: CJ
authors: Graham
authors: Larry S
authors: LS
authors: Andrews
authors: Raymond J
authors: RJ
authors: Papciak
authors: Michael L
authors: ML
authors: Gargas
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis* / Q000592:standards; D004852:Epoxy Compounds / Q000032:analysis* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D012016:Reference Values; D018570:Risk Assessment; D020711:Threshold Limit Values
chemical_list: D002273:Carcinogens; D004852:Epoxy Compounds; C009068:propylene oxide