Print Email Facebook Twitter Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study Title Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study Author Tonk, E.C.M. de Groot, D.M.G. Wolterbeek, A.P.M. Penninks, A.H. Waalkens-Berendsen, I.D.H. Piersma, A.H. van Loveren, H. Publication year 2013 Abstract The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of immune and developmental parameters to ethanol (EtOH), a well-known developmental toxicant with immunomodulatory properties. Adult Wistar rats were exposed to EtOH via drinking water (0, 1.5, 4, 6.5, 9, 11.5 and 14 % (w/v EtOH)) during premating, mating, gestation and lactation and continuation of exposure of the F1 from weaning until killed. Immune assessments were performed at postnatal days (PNDs) 21, 42 and 70. Keyhole limpet hemocyanin (KLH)-specific immune responses were evaluated following subcutaneous immunizations on PNDs 21 and 35. EtOH exposure affected innate as well as adaptive immune responses. The most sensitive immune parameters included white blood cell subpopulations, ConA-stimulated splenocyte proliferation, LPS-induced NO and TNF-α production by adherent splenocytes and KLH-specific immune responses. Most parameters showed recovery after cessation of EtOH exposure after weaning in the 14 % exposure group. However, effects on LPS-induced NO and TNF-α production by adherent splenocytes and KLH-specific parameters persisted until PND 70. The results demonstrate the relative sensitivity to EtOH of especially functional immune parameters and confirm the added value of immune parameters in the EOGRTS. Furthermore, this study identified an expanded KLH-specific parameter set and LPS-induced NO and TNF-α production by adherent splenocytes as valuable parameters that can provide additional information on functional immune effects. © 2012 Springer-Verlag. Subject Life Triskelion BVQS - Quality & Safety TARA - Toxicology and Risk Assessment RAPID - Risk Analysis for Products in DevelopmentEELS - Earth, Environmental and Life Sciences TNO BedrijvenBiomedical InnovationBiologyHealthy LivingBenchmark dose approachDevelopmental immunotoxicityEthanolExtended one-generation reproductive toxicity studyAlcoholConcanavalin ADrinking waterKeyhole limpet hemocyaninLipopolysaccharideNitric oxideTumor necrosis factor alphaAdaptive immunityAdult animalAnimal experimentAnimal modelblood cellCell adhesionCell proliferationCell stimulationCell subpopulationChemical parametersControlled studyCytokine productionDevelopmental parametersDevelopmental toxicityFemaleImmune responseImmunizationImmunological parametersImmunomodulationImmunotoxicityInnate immunityLactationMaleMatingMedical parametersPerinatal periodPriority journalRatReproductive toxicitySpleen cellToxicity testingWistar ratRattus norvegicus To reference this document use: http://resolver.tudelft.nl/uuid:9f901061-0e20-453f-9632-c344bf80dada DOI https://doi.org/10.1007/s00204-012-0940-1 TNO identifier 471493 ISSN 0340-5761 Source Archives of Toxicology, 87 (2), 323-335 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.