Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
Reprod Toxicol. 2011 Nov;32(3):341-8. doi: 10.1016/j.reprotox.2011.08.005. Epub 2011 Sep 10.
To determine relevant endpoints for evaluating developmental immunotoxicity due to juvenile exposure and optimal age of the animals at assessment, a wide range of immunological parameters were assessed in a juvenile toxicity study. Rats were exposed to di-n-octyltin dichloride (DOTC) by gavage from postnatal day (PND) 10 through PND 21 and via the diet after weaning using a benchmark dose (BMD) approach. Immune assessments were performed in male rats on PNDs 21, 42, and 70 and a subset of animals was used to evaluate the T-cell dependent antibody response (TDAR) to Keyhole limpet hemocyanin. Immune effects were more pronounced on PND 21 and 42 and observed at lower doses than developmental effects. The most sensitive immune parameters affected included TDAR parameters and thymocyte subpopulations with lower confidence limits of the benchmark doses (BMDLs) below the overall no-observed-adverse-effect-level (NOAEL) for DOTC reported so far in literature. These findings illustrate the relative sensitivity of the developing immune system for DOTC, the additional value of assessing functional immune parameters, and underscore the relevance of juvenile immunotoxicity testing in view of the risk assessment of chemicals.
为了确定由于幼年暴露和评估时动物的最佳年龄而导致发育性免疫毒性的相关终点，在一项幼年毒性研究中评估了广泛的免疫学参数。大鼠通过灌胃从出生后第 10 天（PND）到第 21 天，以及通过断奶后的饮食，以基准剂量（BMD）方法接触二辛基锡二氯化物（DOTC）。在 PNDs 21、42 和 70 对雄性大鼠进行免疫评估，并对一组动物进行评价以评估对血蓝蛋白的 T 细胞依赖性抗体反应（TDAR）。在 PND 21 和 42 时，免疫效应更为明显，并且在较低剂量下观察到比发育效应更早的出现。受影响的最敏感免疫参数包括 TDAR 参数和胸腺细胞亚群，而 BMD 的置信下限（BMDL）低于迄今为止文献中报告的 DOTC 的总体无不良效应水平（NOAEL）。这些发现说明了发育中免疫系统对 DOTC 的相对敏感性，评估功能性免疫参数的额外价值，并强调了鉴于化学品的风险评估，幼年免疫毒性测试的相关性。
