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Metabolic, reproductive and thyroid effects of bis(2-ethylhexyl) phthalate (DEHP) orally administered to male and female juvenile rats at dose levels derived from children biomonitoring study.
- Source :
-
Toxicology [Toxicology] 2021 Feb 15; Vol. 449, pp. 152653. Date of Electronic Publication: 2020 Dec 09. - Publication Year :
- 2021
-
Abstract
- Bis(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in several items, non-covalently bound to plastics and easily released, since metabolites were found in human matrices. DEHP is an endocrine disrupter and children are particularly vulnerable and susceptible to DEHP effects due to higher exposure levels and developmental stage. A juvenile toxicity study was performed to identify DEHP hazard and mode of action in Sprague-Dawley rats of both sexes during peri-pubertal period - corresponding to childhood phase - from weaning, post-natal day (PND) 23, to full sexual maturity (PND60); the dose levels of 0, 9, 21 and 48 mg/kg bw/day were derived from LIFE PERSUADED biomonitoring study in children. DEHP was administered by gavage for 28 days (5 days/week); timing of preputial separation and vaginal opening was observed during treatment. Histopathological analysis was performed on: adrenals, spleen, liver, thyroid and reproductive organs. The following serum biomarkers were assessed: estradiol, testosterone, anti-Mullerian hormone, tetraiodothyronine, thyroid stimulating hormone, adiponectin and leptin. Gene expression on hypothalamic-pituitary area was focused on follicle stimulating, luteinizing, and thyroid stimulating hormones. The results showed that main targets of DEHP during juvenile period were liver and metabolic system in both sexes, while sex-specific effects were recorded in reproductive system (male rats) and in thyroid (female rats). DEHP exposure during peri-pubertal period at dose levels derived from biomonitoring study in children can induce sex-specific imbalances identifying the juvenile animal model as a sound tool to identify hazards for a reliable risk assessment targeted to children.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Oral
Age Factors
Animals
Animals, Newborn
Child
Diethylhexyl Phthalate administration & dosage
Dose-Response Relationship, Drug
Female
Humans
Male
Plasticizers administration & dosage
Plasticizers metabolism
Plasticizers toxicity
Rats
Rats, Sprague-Dawley
Reproduction physiology
Sexual Maturation physiology
Biological Monitoring methods
Diethylhexyl Phthalate toxicity
Reproduction drug effects
Sexual Maturation drug effects
Thyroid Gland drug effects
Thyroid Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 449
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 33309551
- Full Text :
- https://doi.org/10.1016/j.tox.2020.152653