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 car cinogenic findings as well as relevant metabolism and pharmacoki netic 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 con sistent across species. Two methods, time-exposure concentration product and area under the plasma concentration-time curve (A UC) are used as a basis for calculating effective dose. Scaling of the dose to man from both rat and dog is explored based on phar macokinetic 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 μg/liter over a working lifetime. The use of A UC as a basis for dose from a daily exposure of 1.8 μg/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.