Cancer potencies of heterocyclic amines found in cooked foods.
Quantitative estimates of potential cancer risk associated with eating heterocyclic amines (HAs) in cooked foods and food products, known to be highly mutagenic in the Ames/Salmonella assay and to cause cancer in laboratory animals, rely on estimates of carcinogenic potency from animal bioassay data. New estimates of potential human cancer potency are presented for 10 HAs associated with potential human dietary exposure from cooked-food sources. These estimates differ from previous similar estimates in that they properly reflect the fact that most of these HAs exhibit a pronounced ability to induce tumours at multiple histologically distinct sites within each sex/species tested, and so might be expected to be multipotent carcinogens in humans as well. Thus, in addition to 82 tumour-type-specific potencies estimated for these compounds, 24 additional estimates of aggregate potency (to induce one or more tumour types) were made, using different methods to scale estimated bioassay cancer potency to humans. The currently unknown potency of an additional cooked-food HA was estimated using linear regressions of log-carcinogenic on log-mutagenic potency for the other 10 HAs, some of which were highly significant (e.g. r = 0.85, P < 0.004). The potency estimates obtained are consistent with an upper-bound cancer risk between 10(-3) and 10(-4) for an average lifetime cooked-beef intake of 3.3 g/kg/day (or approx. 0.5 lb/day). Use of these potency estimates to obtain more realistic upper-bound estimates of dietary-HA risk will require detailed HA-exposure assessments.
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Lawrence Livermore National Laboratory, University of California, Livermore 94550.
D000588:Amines / Q000633:toxicity*; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D003296:Cooking; D005260:Female; D005504:Food Analysis; D006571:Heterocyclic Compounds / Q000633:toxicity*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011810:Quinoxalines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D000588:Amines; D002273:Carcinogens; D006571:Heterocyclic Compounds; D009153:Mutagens; D011810:Quinoxalines; C045421:3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine