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. (15th February 2021)

• Record Type: Journal Article
• Authors: Tassinari, Roberta; Tait, Sabrina; Busani, Luca; Martinelli, Andrea; Narciso, Laura; Valeri, Mauro; Gastaldelli, Amalia; Deodati, Annalisa; La Rocca, Cinzia; Maranghi, Francesca
• Is Part Of: Toxicology. Volume 449(2021)
• Publication Date: 2021-02-15
• Subjects: Plasticizer -- Endocrine disrupter -- Sex-related effects -- Peri-pubertal -- NOAEL/LOAEL -- Benchmark dose; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2020.152653
• Languages: English
• ISSNs: 0300-483X

Abstract

Graphical abstract: Highlights: Immature male and female rats are used for identifying DEHP hazards. Dose levels are derived from PERSUADED biomonitoring study in children. Liver, reproductive and metabolic systems are target of DEHP in immature rats. Male pubertal delay and female thyroid tissue alterations are specific effects. Juvenile animal model is a sound tool to identify hazards for children. 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.