Arni P, Ashby J, Castellino S, Engelhardt G, Herbold B A, Priston R A, Bontinck W J
European Chemical Industry Ecology and Toxicology Centre (ECETOC), Brussels, Belgium.
Mutat Res. 1988 Jun;203(3):177-84. doi: 10.1016/0165-1161(88)90102-1.
An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.
本文描述了一种方法，该方法可将化学物质的生殖细胞致突变性评估作为遗传毒性潜力综合评估的一部分。建议首先通过适当的体外研究来确定化学物质的遗传毒性。这应包括使用沙门氏菌突变试验和染色体畸变诱导试验，但在特定情况下可能需要补充试验。如果这两项试验得到阴性结果，则无需进行额外试验。体外被认为具有遗传毒性的物质随后应评估其对啮齿动物的遗传毒性。这通常需要进行骨髓细胞遗传学试验，如果结果为阴性，则在独立组织中进行遗传毒性试验。体内被发现无遗传毒性的物质被视为没有生殖细胞致突变性潜力。体内被发现具有遗传毒性的物质要么被假定具有作为生殖细胞诱变剂的潜力，要么其在这方面的状况可通过适当的生殖细胞致突变性研究来确定。该方法的依据得到了现有实验数据的支持，即生殖细胞诱变剂在体内将表现为体细胞遗传毒素，并且在进行适当实验的情况下，这些将在体外被检测为遗传毒素。建议进行适当和充分的研究比进行一套严格规定的试验更有价值。
