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Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Ethylene Oxide.

PB88188784

Publication Date	1987
Personal Author	Hattis, D.
Page Count	227
Abstract	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 (75218) 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 is available showing carcinogenic response of rats and mice to ethylene-oxide. Equations were 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.
Keywords	Ethylene oxide Risk Carcinogen Disinfectants Occupational diseases Kinetics Rats Exposure Alkylation Computer applications Metabolism Mice Humans Regression analysis Toxicity Dosage Pharmacokinetics Toxic substances Occupational safety and health
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	68G - Environmental Health & Safety 94D - Job Environment 57U - Public Health & Industrial Medicine 57Y - Toxicology
Corporate Authors	Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.; National Inst. for Occupational Safety and Health, Rockville, MD.; National Inst. of Environmental Health Sciences, Research Triangle Park,
Supplemental Notes	Sponsored by National Inst. for Occupational Safety and Health, Rockville, MD., and National Inst. of Environmental Health Sciences, Research Triangle Park, NC.
Document Type	Technical Report
NTIS Issue Number	198815

Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Ethylene Oxide.

Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Ethylene Oxide.
PB88188784

Publication Date	1987
Personal Author	Hattis, D.
Page Count	227
Abstract	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 (75218) 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 is available showing carcinogenic response of rats and mice to ethylene-oxide. Equations were 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.
Keywords	Ethylene oxide Risk Carcinogen Disinfectants Occupational diseases Kinetics Rats Exposure Alkylation Computer applications Metabolism Mice Humans Regression analysis Toxicity Dosage Pharmacokinetics Toxic substances Occupational safety and health
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	68G - Environmental Health & Safety 94D - Job Environment 57U - Public Health & Industrial Medicine 57Y - Toxicology
Corporate Authors	Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.; National Inst. for Occupational Safety and Health, Rockville, MD.; National Inst. of Environmental Health Sciences, Research Triangle Park,
Supplemental Notes	Sponsored by National Inst. for Occupational Safety and Health, Rockville, MD., and National Inst. of Environmental Health Sciences, Research Triangle Park, NC.
Document Type	Technical Report
NTIS Issue Number	198815