Pharmacokinetic/mechanism-based analysis of the carcinogenic risk of ethylene oxide

Technical Report · Sat Aug 01 04:00:00 EDT 1987

DOI:https://doi.org/10.2172/7067804· OSTI ID:7067804

Hattis, D

An attempt was made to build an integrated series of pharmacokinetic models for low-molecular-weight alkylating agents in efforts to expand the understanding of risk assessment for various occupational carcinogens. The purpose was to allow for better assessment of biologically effective doses of activated metabolites delivered to target tissues and to arrive at a better translation of such units between species. The approach to pharmacokinetic modeling of ethylene oxide was defined, and specific results were presented. Longer elimination was predicted to increase internal dose, so that greater internal doses would be expected in man compared to rodents. Lower respiration per body weight in man would decrease absorption rate, offsetting the higher predicted internal dose. In terms of human cancer risk, it is stated that substantial data are available showing carcinogenic response of rats and mice to ethylene oxide. Equations are presented showing the risk resulting for different sites, species, and sexes using the measure of delivered dose in a multistage model. Implications for overall human cancer risk from 45 years 8 hours per day occupational exposure to 1 part per million ethylene oxide were presented. Doses used in analysis did not yield markedly divergent estimates of human risk. The authors conclude that, for a simple direct-acting alkylator like ethylene oxide, traditional approaches for dose and risk projection across species are supported by pharmacokinetic-based analysis.

• Research Organization: Massachusetts Inst. of Tech., Cambridge (USA). Center for Technology, Policy and Industrial Development
• OSTI ID: 7067804
• Report Number(s): PB-88-188784/XAB; CTPID-87-1
• Country of Publication: United States
• Language: English

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500200 -- Environment
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54 ENVIRONMENTAL SCIENCES
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99 GENERAL AND MISCELLANEOUS
ALKYLATION
ANIMALS
CARCINOGENS
CHEMICAL REACTIONS
DISINFECTANTS
GERMICIDES
KINETICS
MAMMALS
MATHEMATICS
METABOLISM
MICE
OCCUPATIONAL DISEASES
RATS
REGRESSION ANALYSIS
RISK ASSESSMENT
RODENTS
STATISTICS
TOXICITY
VERTEBRATES