title: Developmental immunotoxicity in male rats after juvenile exposure to di-n-octyltin dichloride (DOTC).
abstract: 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.
authors.affiliation: Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands. ilse.tonk@rivm.nl
authors.forename: Elisa C M
authors.initials: EC
authors.lastname: Tonk
authors.forename: Aart
authors.initials: A
authors.lastname: Verhoef
authors.forename: Liset J J
authors.initials: LJ
authors.lastname: de la Fonteyne
authors.forename: Ine D H
authors.initials: ID
authors.lastname: Waalkens-Berendsen
authors.forename: André P M
authors.initials: AP
authors.lastname: Wolterbeek
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D016207:Cytokines / Q000276:immunology; D004785:Environmental Pollutants / Q000633:toxicity*; D004909:Erythrocyte Indices / Q000187:drug effects; D005260:Female; D006400:Hematocrit; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000254:growth & development; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects / Q000254:growth & development
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D007074:Immunoglobulin G; D009947:Organotin Compounds; D009569:Nitric Oxide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; C020297:di-n-octyltin dichloride