Simmons J E, Berman E
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
J Toxicol Environ Health. 1989;27(3):275-86. doi: 10.1080/15287398909531299.
The ability to predict the biological effect of complex waste mixtures from chemical characterization data was examined by comparing observed mortality to that predicted by a mathematical additivity model with literature LD50 values for the chemicals identified in the mixtures. Male F344 rats were exposed by gavage to 1 of 10 samples of complex industrial waste. Seven of the 10 waste samples caused death within 24 h of administration at dosages ranging from 1 to 5 ml/kg body weight. Two of the 7 lethal waste samples produced 100% mortality at a dosage of 2.5 ml/kg; another 2 waste samples produced 100% mortality at 5 ml/kg. The partial chemical analysis, although providing more extensive information on chemical composition than might normally be available for most complex waste mixtures, was not sufficient to distinguish lethal from nonlethal waste samples or to indicate lethal potency. Possible explanations for the apparent inability to predict readily lethality from the chemical characterization data include the possible inappropriateness of an additivity model due to the presence of interactions, such as synergism or antagonism; the kinetics of chemical absorption, distribution, and elimination, which may be affected by administration of the chemical in a complex matrix; and the presence of unidentified chemicals in the mixture that may have contributed to the observed toxicity.
通过将观察到的死亡率与数学加和模型预测的死亡率进行比较，该模型采用混合物中已鉴定化学物质的文献半数致死剂量（LD50）值，来检验从化学特征数据预测复杂废物混合物生物效应的能力。雄性F344大鼠经口灌胃接触10种复杂工业废物样品中的1种。10个废物样品中有7个在以1至5毫升/千克体重的剂量给药后24小时内导致死亡。7个致死性废物样品中有2个在2.5毫升/千克的剂量下产生了100%的死亡率；另外2个废物样品在5毫升/千克的剂量下产生了100%的死亡率。部分化学分析虽然比大多数复杂废物混合物通常可获得的信息提供了更广泛的化学成分信息，但不足以区分致死性和非致死性废物样品，也无法表明致死效力。从化学特征数据明显无法轻易预测致死性的可能解释包括：由于存在相互作用（如协同作用或拮抗作用），加和模型可能不合适；化学物质吸收、分布和消除的动力学可能受到在复杂基质中施用化学物质的影响；以及混合物中存在可能导致观察到的毒性的未鉴定化学物质。
