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Title: Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

Abstract

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of themore » developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less

Authors:
 [1];  [2]; ;  [3];  [1];  [2];  [3];  [4]
  1. Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands)
  2. (RIVM), Bilthoven (Netherlands)
  3. Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands)
  4. (Netherlands)
Publication Date:
OSTI Identifier:
22215282
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 260; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALLERGY; ANDROGENS; BENCHMARKS; CORN OIL; DOSES; ENVIRONMENT; JUVENILES; PHTHALATES; RATS; SENSITIVITY; TOXICITY

Citation Formats

Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Verhoef, Aart, Gremmer, Eric R., Loveren, Henk van, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Piersma, Aldert H., and Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.01.018.
Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Verhoef, Aart, Gremmer, Eric R., Loveren, Henk van, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Piersma, Aldert H., & Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht. Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate. United States. doi:10.1016/J.TAAP.2012.01.018.
Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Verhoef, Aart, Gremmer, Eric R., Loveren, Henk van, Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Piersma, Aldert H., and Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht. Sun . "Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate". United States. doi:10.1016/J.TAAP.2012.01.018.
@article{osti_22215282,
title = {Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate},
author = {Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl and Laboratory for Health Protection Research, National Institute for Public Health and the Environment and Verhoef, Aart and Gremmer, Eric R. and Loveren, Henk van and Laboratory for Health Protection Research, National Institute for Public Health and the Environment and Piersma, Aldert H. and Institute for Risk Assessment Sciences, Veterinary Faculty, Utrecht University, Utrecht},
abstractNote = {The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.},
doi = {10.1016/J.TAAP.2012.01.018},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 260,
place = {United States},
year = {2012},
month = {4}
}