Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
Toxicol Lett. 2011 Jul 28;204(2-3):156-63. doi: 10.1016/j.toxlet.2011.04.027. Epub 2011 Apr 30.
Developmental immunotoxicity assessment is considered ready for inclusion in developmental toxicity studies. Further evaluation of proposed and additional assays is needed to determine their utility in assessing developmental immunotoxicity. In this study, a wide range of immunological parameters was included in an extended one-generation reproductive toxicity protocol. F(0) Wistar rats were exposed to DOTC via the feed (0, 3, 10, and 30mg/kg) during pre-mating, mating, gestation and lactation and subsequently F(1) were exposed from weaning until sacrifice. Immune assessments by several immune parameters were performed at PNDs 21, 42 and 70. The T cell-dependent antibody response to Keyhole Limpet hemocyanin (KLH) was assessed following subcutaneous immunizations with KLH on PNDs 21 and 35 and the delayed-type hypersensitivity response (DTH) against KLH was evaluated at PND 49. No effects were found on PND 21. While effects on lymphocyte subpopulations in the thymus were only observed in the 30mg/kg group on PND 42, effects on lymphocyte subpopulations in the spleen were found in the 30mg/kg group on both PNDs 42 and 70. The DTH response already showed an effect at 3mg/kg and was the overall critical endpoint. The results from this study support the inclusion of splenocyte subpopulation parameters in developmental toxicity studies and identified the DTH response as an important functional parameter.
发育免疫毒性评估被认为已准备好纳入发育毒性研究。需要进一步评估拟议和额外的检测方法，以确定它们在评估发育免疫毒性方面的效用。在这项研究中，广泛的免疫学参数被纳入了一个扩展的一代生殖毒性研究方案中。F(0)Wistar 大鼠通过饲料（0、3、10 和 30mg/kg）在交配前、交配、妊娠和哺乳期接触 DOTC，随后 F(1)从断奶到处死期间接触 DOTC。在 PNDs 21、42 和 70 时通过几种免疫参数进行免疫评估。在 PNDs 21 和 35 时通过皮下免疫 Keyhole Limpet hemocyanin（KLH）进行 T 细胞依赖性抗体反应评估，并在 PND 49 时评估对 KLH 的迟发型超敏反应（DTH）。在 PND 21 时未发现任何影响。虽然在 PND 42 时仅在 30mg/kg 组观察到对胸腺中淋巴细胞亚群的影响，但在 PNDs 42 和 70 时在 30mg/kg 组观察到对脾中淋巴细胞亚群的影响。DTH 反应已经在 3mg/kg 时显示出效果，是整体关键终点。这项研究的结果支持将脾细胞亚群参数纳入发育毒性研究，并确定 DTH 反应是一个重要的功能参数。
