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Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study
- 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.
- Subjects :
- Male
Reproductive toxicity
Biomedical Innovation
Wistar rat
Cytokine production
Immunological parameters
Concanavalin A
Immunotoxicity
Cell proliferation
Priority journal
Innate immunity
Medical parameters
Mating
Cell stimulation
Life Triskelion BV
Benchmark dose approach
Keyhole limpet hemocyanin
Spleen cell
Developmental immunotoxicity
QS - Quality & Safety TARA - Toxicology and Risk Assessment RAPID - Risk Analysis for Products in Development
Female
Alcohol
Healthy Living
Adult animal
Cell subpopulation
Adaptive immunity
chemical and pharmacologic phenomena
Lipopolysaccharide
Chemical parameters
Environmental and Life Sciences TNO Bedrijven
EELS - Earth
Immunomodulation
blood cell
Drinking water
Lactation
Animal model
Animal experiment
Immune response
Biology
Ethanol
Tumor necrosis factor alpha
Cell adhesion
Nitric oxide
biochemical phenomena, metabolism, and nutrition
Rattus norvegicus
Developmental parameters
Extended one-generation reproductive toxicity study
Developmental toxicity
Perinatal period
Toxicity testing
Rat
Immunization
Controlled study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.dris...00893..be169157ae2a1ec9eb726e02c4409e3a