Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, we estimated the average intakes of HAs, based on analyses of the concentrations of HAs in cooked foods and data from a dietary survey of the US population and quantified the cancer potencies of the individual compounds using dose-response data from animal bioassays. Measured concentrations of HAs in cooked foods were taken from a major review of the open literature. Only those concentrations that were associated with normal cooking conditions were chosen for use in estimating dietary intakes. The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989. Dietary intakes of the five principal HAs in descending order were 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (A alpha C) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > A alpha C. An upper-bound estimate of the incremental cancer risk is 1.1 x 10(-4), using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (approximately 80%) to total risk.

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An integrated, quantitative approach to incorporating both uncertainty and interindividual variability into risk prediction models is described. Individual risk R is treated as a variable distributed in both an uncertainty dimension and a variability dimension, whereas population risk I (the number of additional cases caused by R) is purely uncertain. I is shown to follow a compound Poisson-binomial distribution, which in low-level risk contexts can often be approximated well by a corresponding compound Poisson distribution. The proposed analytic framework is illustrated with an application to cancer risk assessment for a California population exposed to 1,2-dibromo-3-chloropropane from ground water.

Heterocyclic amines ( HAs ) formed in fried, broiled or grilled meats are potent mutagens that increase rates of colon, mammary, prostate and other cancers in bioassay rodents. Studies of how human dietary HA exposures may affect cancer risks have so far relied on fairly crudely defined HA -exposure categories. Recently, an integrated, quantitative approach to HA -exposure assessment ( HAEA ) was developed to estimate compound -specific intakes for particular individuals based on corresponding HA -concentration estimates that reflect their meat -type, intake -rate, cooking -method and meat -doneness preferences. This method was applied in the present study to U.S. national Continuing Survey of Food Intakes by Individuals ( CSFII ) data on meats consumed and cooking methods used by > 25,000 people, after adjusting for underreported energy intake and conditional on meat -doneness preferences estimated from additional survey data. The U.S. population average lifetime time -weighted average of total HAs consumed was estimated to be $9 ng / kg / day, with 2 -amino -1 -methyl -6 -phenylimidazo [ 4,5 -b ] pyridine ( PhIP ) estimated to comprise about two thirds of this intake. Pan -fried meats were the largest source of HA in the diet and chicken the largest source of HAs among different meat types. Estimated total HA intakes by male vs. female children were generally similar, with those by ( 0 -to 15 -year -old ) children $25% greater than those by ( 16 + -year -old ) adults. Race -, age -and sex -specific mean HA intakes were estimated to be greatest for African American males, who were estimated to consume $2 -and $3 -fold more PhIP than white males at ages < 16 and 30 + years, respectively, after considering a relatively greater preference for more well -done items among African Americans based on national survey data. This difference in PhIP intakes may at least partly explain why prostate cancer ( PC ) kills $2 -fold more African American than white men, in view of experimental data indicating that PhIP mutates prostate DNA and causes prostate tumors in rats. Journal of Exposure Analysis and Environmental Epidemiology ( 2001 ) 11, 155 ± 168.

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