Developmental Toxicology Division, Industrial Toxicology Research Center, M.G. Marg, LucknowIndia.
Toxicol Mech Methods. 2005;15(3):155-80. doi: 10.1080/15376520590945667.
The advent of the industrial revolution has seen a significant increase in the number of new chemical entities (NCEs) released in the environment. It becomes imperative to check the toxic potential of NCEs to nontarget species before they are released for commercial purposes because some of these may exert genotoxicity, mutagenicity, or carcinogenicity. Exposure to such compounds produces chemical changes in DNA, which are generally repaired by the DNA repair enzymes. However, DNA damage and its fixation may occur in the form of gene mutations, chromosomal damage, and numerical chromosomal changes and recombination. This may affect the incidence of heritable mutations in man and may be transferred to the progeny or lead to the development of cancer. Hence, adequate tests on NCEs have to be undertaken for the risk assessment and hazard prediction. Compounds that are positive in tests that detect such damages have the potential to be human mutagens/carcinogens. Only long-term animal bioassays, involving lifetime studies on animals, were used earlier to classify substances as mutagens/carcinogens. These tests were cumbersome and time consuming and required a lot of facilities and personnel. Short-term tests, therefore, were brought into practice. A "battery" of three to four of these short-term tests has been proposed now by a number of regulatory authorities for the classification of compounds as mutagenic or carcinogenic. This review deals with the current status of these short-term tests.
工业革命的出现导致环境中新化学实体 (NCE) 的数量显著增加。在这些物质因商业目的而被释放之前,检查它们对非目标物种的潜在毒性变得至关重要,因为其中一些物质可能具有遗传毒性、致突变性或致癌性。接触这些化合物会导致 DNA 发生化学变化,这些变化通常会被 DNA 修复酶修复。然而,DNA 损伤及其固定可能以基因突变、染色体损伤和数目染色体变化和重组的形式发生。这可能会影响人类遗传突变的发生率,并可能传递给后代或导致癌症的发展。因此,必须对 NCE 进行充分的测试,以进行风险评估和危害预测。在检测此类损伤的测试中呈阳性的化合物有可能成为人类诱变剂/致癌物。以前,只有长期动物生物测定,包括对动物进行终生研究,才能将物质分类为诱变剂/致癌物。这些测试繁琐且耗时,需要大量的设施和人员。因此,短期测试已经付诸实践。现在,许多监管机构提出了三到四个这样的短期测试“组合”,用于将化合物分类为致突变或致癌。这篇综述涉及这些短期测试的现状。