Risk assessment and oncodynamics of ethylene oxide as related to occupational exposure.
Two rat inhalation bioassays have been integrated into the risk assessment on the carcinogenicity of ethylene oxide (EO). The carcinogenic findings as well as relevant metabolism and pharmacokinetic data are reviewed. Brain tumors were selected as the endpoint for the assessment of risk because of the indication that adverse effects on the nervous system, related to EO exposure, were consistent across species. Two methods, time-exposure concentration product and area under the plasma concentration-time curve (AUC) are used as a basis for calculating effective dose. Scaling of the dose to man from both rat and dog is explored based on pharmacokinetic studies. Two different mathematical risk extrapolation models, the probit and the multi-stage, are used to estimate the cancer risk for daily exposures to EO of 1.8 microgram/liter over a working lifetime. The use of AUC as a basis for dose from a daily exposure of 1.8 microgram/liter over a working lifetime gives the higher risk rates (90-142/10,000 workers). The implication of the simulated dose using plasma concentrations versus the time-concentration product approach is discussed in relation to threshold effects.
U.S. Environmental Protection Agency, Washington, D.C.
R P
RP
Beliles
J C
JC
Parker
D000395:Air Pollutants, Occupational / Q000633:toxicity; D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced; D002273:Carcinogens; D004305:Dose-Response Relationship, Drug; D005027:Ethylene Oxide / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012306:Risk
D000395:Air Pollutants, Occupational; D002273:Carcinogens; D005027:Ethylene Oxide