EFFECTS OF THE NON-PHTHALATE PLASTICIZER DEHT ON THE MORPHOPHYSIOLOGY OF THE MALE GENITAL SYSTEM AND INTERACTIONS WITH THE INTESTINAL MICROBIOTA IN RATS.

• Grant number: 24/19192-1
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Juliana Elaine Perobelli
• Grantee: Juliana Elaine Perobelli
• Host Institution: Instituto do Mar (IMar). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Maria Christina Werneck de Avellar ; Michael Zimmermann

Abstract

Plasticizers are chemical additives that confer flexibility, lightness, and durability to plastic polymers. Over the past decade, commonly used phthalate plasticizers such as Di(2-ethylhexyl) phthalate (DEHP) and Bisphenol A (BPA) have been increasingly restricted in food packaging, toys, and medical devices due to their well-documented health risks, including endocrine disruption and impaired fertility. In response to these concerns, non-phthalate plasticizers, such as bis(2-ethylhexyl) terephthalate (DEHT), have been introduced as potentially safer alternatives for human exposure. However, there remains a significant knowledge gap regarding the potential adverse effects of these alternatives, particularly in relation to reproductive function, hepatic and renal toxicity, and their interactions with the intestinal microbiota (IM), especially when considering environmentally relevant exposure levels. This research aims to evaluate the impact of DEHT on the morphophysiology of the male reproductive system, liver, kidneys, and its interaction with the IM in male rats, which will be orally exposed to environmentally relevant doses of the plasticizer over a period of 65 days. Additionally, the study will explore the role of IM in the metabolism and toxicity of DEHT by comparing rats with healthy IM (eubiosis) to those with antibiotic-induced dysbiosis through the administration of non-absorbable antibiotics (nABX). The outcomes of this study will provide valuable insights into the toxicological profile of alternative plasticizers, shedding light on the cellular signaling pathways and metabolic processes involved, as well as the influence of IM in modulating these effects. Furthermore, these findings will contribute to ongoing discussions surrounding plastic pollution and pave the way for new research and mitigation strategies aimed at reducing potential health risks to both humans and wildlife. (AU)