Print Email Facebook Twitter Developmental immunotoxicity of methylmercury: The relative sensitivity of developmental and immune parameters Title Developmental immunotoxicity of methylmercury: The relative sensitivity of developmental and immune parameters Author Tonk, E.C.M. de Groot, D.M.G. Penninks, A.H. Waalkens - Berendsen, I.D.H. Wolterbeek, A.P.M. Slob, W. Piersma, A.H. van Loveren, H. TNO Kwaliteit van Leven Publication year 2010 Abstract Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of different immune and developmental parameters. Mated female Wistar rats were dosed daily by gavage with methylmercury (0, 0.1, 0.4, 0.7, 1.0, 1.5, and 2.0 mg/kg BW/day) from gestational day 6 to postnatal day (PND) 10. In addition to general, reproductive, and developmental parameters, a wide range of immunological parameters were assessed in male offspring at PNDs 21, 42, and 70. The T cell-dependent antibody response to keyhole limpet hemocyanin (KLH) was assessed following sc immunizations on PNDs 21 and 35. Dose-response data were analyzed using the benchmark dose (BMD) approach by fitting dose-response models to the various endpoints. Methylmercury induced effects on developmental parameters, such as growth parameters and pup mortality. Effects on the immune system were found at doses without observed developmental toxicity. Immune effects differed at the three time points and consisted mainly of effects on functional parameters. The parameter with the lowest 5% lower confidence bound of the BMD (BMDL) was the primary KLH-specific IgG antibody response, which showed a dose-dependent decrease with a BMD of 0.039 mg/kg BW/day (CI 0.010-0.12). These data show the relatively high sensitivity of the developing immune system and thereby illustrate the relevance of testing immune parameters in reproductive and developmental toxicity testing protocols. © The Author 2010. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. Subject ToxicologyBiomedical ResearchBenchmark doseDevelopmental immunotoxicityDevelopmental toxicityDose-response modelingMethylmercuryPerinatal exposureRatgamma interferoninterleukin 10interleukin 13interleukin 2interleukin 4interleukin 6keyhole limpet hemocyaninmethylmercuryT lymphocyte antibodyadherent cellanimal tissueantibody responsearticlebasophilbody weightCD3+ T lymphocyteCD4 CD8 ratioCD8+ T lymphocyteclinical evaluationcontrolled studycytokine productiondelayed hypersensitivitydevelopmental screeningdiagnostic valueenvironmental exposureepididymiserythrocytefemalegestational ageimmunological parametersimmunotoxicitykidney massleukocyte countlitter sizeliver weightlymphocyte proliferationnatural killer cellnewborn mortalitynonhumanratreticulocyte countsensitivity and specificityspleen cellspleen weightstillbirthtestis weightthrombocyte countthymusweight reduction To reference this document use: http://resolver.tudelft.nl/uuid:4c58826c-8d2c-4f4b-9aa9-901e2ec2ea52 TNO identifier 409827 ISSN 1096-6080 Source Toxicological Sciences, 117 (2), 325-335 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.