Reuter Ulrike, Heinrich-Hirsch Barbara, Hellwig Jürgen, Holzum Beate, Welsch Frank
BUA-Büro Munich, Technical University of Munich, Hohenbachernstrasse 15-17, 85350 Freising-Weihenstephan, Germany.
Regul Toxicol Pharmacol. 2003 Aug;38(1):17-26. doi: 10.1016/s0273-2300(03)00076-x.
The Advisory Committee on Existing Chemicals (BUA) of the Federal Republic of Germany convened a panel with expertise in reproductive and developmental toxicology to evaluate the OECD Screening Tests 421 (Reproduction/Developmental Toxicity Screening Test) and 422 (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test) with respect to their ability to unmask any potential toxic effects on reproduction. The original assignment for that panel was to "validate" those screening tests. However, the panel members recognized beforehand that this was actually an impossible task because of lack of a sufficient database. Only five chemicals with known reproductive toxicity had been examined following the OECD Screening Test Guidelines 421 or 422. A comparison of these test results with those of the definitive OECD Test Guidelines 414, 415, 416, or additional investigations could, therefore, only have been made with this very limited number of chemicals that had also undergone evaluation by one of the test guidelines cited. In each case biological properties relevant to reproductive toxicity were also indicated by the OECD Screening Tests 421 or 422. This communication reviews the main differences in study design of OECD Screening Test Guidelines 421 and 422 compared to those definitive test guidelines of similar study design for reproduction or developmental toxicity (especially with the one-generation study, OECD Test Guideline 415). The very limited possibilities of detecting late postnatal and postlactational manifestations are emphasized, as is the low statistical power of the OECD Screening Tests 421 and 422. Furthermore, the very limited ability to unmask teratogenicity is delineated. The outcome of screening tests was evaluated based on the results of 57 studies conducted according to the OECD Test Guideline 421 or 422. The test results were categorized according to the incidence of toxic effects on reproduction in the parent animals or their offspring and related to general toxic effects. Based on the ranking of these results, recommendations regarding setting rational priorities for further evaluations of existing chemicals' reproductive hazards are made. In general, the reviewer panel supports the OECD position that the screening tests are useful for initial hazard assessment and can contribute to the decision-making process on setting priorities for further test requirements. The panel also agrees with the OECD statement that the OECD Screening Tests 421 and 422 are neither an alternative to definitive tests (i.e., OECD Test Guidelines 414, 415, and 416) nor are they intended as their replacement.
德意志联邦共和国现有化学品咨询委员会（BUA）召集了一个在生殖和发育毒理学方面具有专业知识的小组，以评估经合组织筛选试验421（生殖/发育毒性筛选试验）和422（重复剂量毒性联合研究与生殖/发育毒性筛选试验）揭示对生殖的任何潜在毒性作用的能力。该小组最初的任务是“验证”这些筛选试验。然而，小组成员事先认识到，由于缺乏足够的数据库，这实际上是一项不可能完成的任务。按照经合组织筛选试验指南421或422，仅对五种已知具有生殖毒性的化学品进行了检测。因此，只能将这些试验结果与经合组织确定的试验指南414、415、416的结果或其他调查结果进行比较，而这些化学品的数量非常有限，且它们也已通过上述提及的其中一项试验指南进行了评估。在每种情况下，经合组织筛选试验421或422也都表明了与生殖毒性相关的生物学特性。本通讯回顾了经合组织筛选试验指南421和422与类似生殖或发育毒性研究设计的确定性试验指南（特别是一代研究，经合组织试验指南415）在研究设计上的主要差异。强调了检测出生后晚期和哺乳期后表现的可能性非常有限，以及经合组织筛选试验421和422的统计效力较低。此外，还阐述了揭示致畸性的能力非常有限。根据按照经合组织试验指南421或422进行的57项研究结果，对筛选试验的结果进行了评估。试验结果根据对亲代动物或其后代生殖毒性作用的发生率进行分类，并与一般毒性作用相关联。基于这些结果的排名，就为进一步评估现有化学品的生殖危害设定合理优先级提出了建议。总体而言，评审小组支持经合组织的立场，即筛选试验有助于初步危害评估，并可为确定进一步试验要求的优先级的决策过程做出贡献。该小组还同意经合组织的声明，即经合组织筛选试验421和422既不是确定性试验（即经合组织试验指南414、415和416）的替代方法，也不是要取代它们。
