Bogen K T
Lawrence Livermore National Laboratory, University of California, Livermore 94550.
Food Chem Toxicol. 1994 Jun;32(6):505-15. doi: 10.1016/0278-6915(94)90106-6.
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.
已知杂环胺(HAs)在烹饪食品和食品中具有高度致突变性,并能在实验动物中诱发癌症,对食用这些物质所带来的潜在癌症风险进行定量评估,依赖于从动物生物测定数据得出的致癌效力估计值。本文给出了与烹饪食物来源的潜在人类膳食暴露相关的10种杂环胺的潜在人类癌症效力新估计值。这些估计值与先前的类似估计值不同,因为它们恰当地反映了这样一个事实,即这些杂环胺中的大多数在每个测试的性别/物种中,都表现出在多个组织学上不同的部位诱发肿瘤的显著能力,因此预计在人类中也可能是多能致癌物。因此,除了为这些化合物估计的82种肿瘤类型特异性效力外,还使用不同方法将估计的生物测定癌症效力换算到人类,得出了24种额外的总效力估计值(诱发一种或多种肿瘤类型)。利用其他10种杂环胺的致癌效力对数与致突变效力对数的线性回归,估计了另一种烹饪食物杂环胺目前未知的效力,其中一些回归具有高度显著性(例如,r = 0.85,P < 0.004)。对于平均终生烹饪牛肉摄入量为3.3 g/kg/天(或约0.5磅/天)的情况,所获得的效力估计值与10^(-3)至10^(-4)之间的上限癌症风险一致。要使用这些效力估计值来获得更现实的膳食杂环胺风险上限估计值,将需要进行详细的杂环胺暴露评估。