Preussmann R
Arch Toxicol Suppl. 1978(1):69-84. doi: 10.1007/978-3-642-66896-8_7.
One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of "no-adverse-effect-levels". Arguments in favour of the postulated "irreversibility" of carcinogenic effects are based on dose-response studies, single-dose and multi-generation experiments as well as on the concept of somatic mutation as the first steps in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero-tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes never should be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available. Several systems of short-term tests as screening methods are based on mutagenicity tests and offer many advantages. Their critical evaluation is of utmost importance. Examples of some relevant problems to be discussed include nitrosamines in food products and their formation from ingested precursors; the migration of vinyl chloride from PVC food packing material; the occurrence of low levels of chloroform in drinking water.
评估潜在致癌性食品添加剂和污染物时的一个主要问题是阈值问题,或者更确切地说是“无不良反应水平”问题。支持致癌作用假定“不可逆性”的论据基于剂量反应研究、单剂量和多代实验,以及体细胞突变作为致癌作用第一步的概念,随后在细胞复制过程中诱导缺陷会传递下去。将高剂量动物实验结果外推至人类低暴露和低发病率情况的问题尚未得到令人满意的解决。可能的实际后果包括零容忍、低风险下的可接受阈值和安全系数。可接受摄入量绝不应被视为常量,一旦有关于安全性评估的新事实,就应加以改变。作为筛选方法的几种短期测试系统基于致突变性测试,具有许多优点。对它们进行批判性评估至关重要。一些有待讨论的相关问题的例子包括食品中的亚硝胺及其由摄入前体形成的情况;氯乙烯从聚氯乙烯食品包装材料中的迁移;饮用水中低水平氯仿的出现。