Developmental immunotoxicity of di-n-octyltin dichloride (DOTC) in an extended one-generation reproductive toxicity study

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. F0 Wistar rats were exposed to DOTC via the feed (0, 3, 10, and 30 mg/kg) during pre-mating, mating, gestation and lactation and subsequently F1 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 30 mg/kg group on PND 42, effects on lymphocyte subpopulations in the spleen were found in the 30 mg/kg group on both PNDs 42 and 70. The DTH response already showed an effect at 3 mg/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.

► Further evaluation of immune assays is needed to determine their utility in assessing developmental immunotoxicity. ► Splenocyte subpopulation parameters are relevant for inclusion in developmental toxicity studies. ► The DTH response is an important functional parameter. ► Assessment on PND 70 ensures mature functionality of immune parameters, whereas assessment on PND 42 can pick up transient, but not necessarily less relevant effects.