Abstract：
The European Union (EU) Chemicals Strategy for Sustainability regards chemicals that affect the immune system among the most harmful ones. The Extended One-Generation Reproductive Toxicity study (EOGRTS; Organisation for Economic Co-Operation and Development (OECD) Test Guideline (TG) 443), addresses, among others, potential effects of chemicals on development. In specific cases, the EOGRTS is performed with addition of a so-called cohort 3, that addresses potential effects on the developing immune system, by means of a central assay measuring the T-cell dependent antibody response (TDAR). This assay is based on an interplay of antigen presentation, T-cell help and antibody production by B-cells, and together comprises a functional immune response. In the context of the EOGRTS review project of the European Chemicals Agency (ECHA), we evaluated 15 available TDARs for compliance with conduct and reporting requirements. Collectively, the majority of the TDAR studies were considered to be adequately conducted. We however observed: (i) the protocols differed by the antigen used (sheep red blood cells (SRBC) or KLH), the route of administration (intravenous, intraperitoneal, or subcutaneous), prime or prime/boost immunizations, and whether IgG was measured. (ii) There was major variation in the effects of the positive control for immunosuppression, cyclophosphamide. (iii) Proficiency was not always shown. (iv) Statistical analysis was not always done or reported. (v) Results of effects on lymphocyte populations or other immunotoxicity observations obtained in cohort 1 (or 2) of the EOGRTS were not always discussed together with results of the TDAR. Taken together, next to an improved quality of reporting, this may suggest a need to better define the conduct of the TDAR in OECD TG 443 and OECD Guidance Document (GD) 151, at least for certain aspects.
摘要：
欧盟化学品可持续发展战略将影响免疫系统的化学品视为最有害的化学品。延长的一代生殖毒性研究（EOGRTS；经济合作与发展组织（OECD）测试指南（TG）443），地址,其中,化学品对发展的潜在影响。在特定情况下,EOGRTS是在添加所谓的队列3的情况下进行的，该队列解决了对发育中的免疫系统的潜在影响，通过测量T细胞依赖性抗体应答(TDAR)的中心测定。该测定法基于抗原呈递的相互作用，T细胞帮助和B细胞产生抗体，并一起包含功能性免疫应答。在欧洲化学品管理局(ECHA)的EOGRTS审查项目的背景下，我们评估了15个可用的TDAR是否符合行为和报告要求.总的来说，大多数TDAR研究被认为是充分进行的.然而，我们观察到：（i）使用的抗原（绵羊红细胞（SRBC）或KLH）不同的方案，给药途径(静脉注射，腹膜内,或皮下)，初次或初次/加强免疫接种，以及是否测量IgG。（ii）免疫抑制阳性对照的效果有很大差异，环磷酰胺.(iii)并不总是表现出熟练程度。（iv）并不总是进行或报告统计分析。(v)在EOGRTS的组群1(或2)中获得的对淋巴细胞群体或其他免疫毒性观察的影响的结果并不总是与TDAR的结果一起讨论。一起来看,除了提高报告质量之外，这可能表明需要在OECDTG443和OECD指导文件（GD）151中更好地定义TDAR的行为，至少在某些方面。
