Full Breakdown
Early DEHP Exposure Linked to Heightened Anxiety in Adult Male Rats
6/19/2026, 11:00:28 AM
Study Demonstrates Anxiety Elevation After Prenatal DEHP Exposure
Male rats that received the plasticizer di-(2-ethylhexyl) phthalate (DEHP) throughout gestation and the early post-natal period displayed increased anxiety-related behavior as adults. Anxiety was assessed at 70 days of age using the elevated plus maze (EPM), a standard test that measures rodents’ aversion to open and elevated spaces.
Context of DEHP Use and Endocrine Disruption
DEHP is added to a wide array of consumer items—including medical devices, toys, shower curtains, and raincoats—to increase flexibility. Prior investigations have linked DEHP and its metabolites to disruptions of reproductive and nervous system function in both animal models and humans, classifying it as an endocrine-disrupting chemical (EDC).
Experimental Design and Key Personnel
The study was conducted by a team at the University of Buenos Aires School of Medicine, led by Osvaldo Juan Ponzo, M.D., Ph.D. Findings were presented at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois. Pregnant female rats were administered daily oral doses of DEHP from the first day of pregnancy until their litters were weaned. Only male offspring were retained for behavioral testing.
Behavioral Findings and Quantitative Results
In the EPM, DEHP-exposed rats entered the open arms less frequently, spent a shorter cumulative time in those arms, lingered longer in the enclosed arms, and exhibited prolonged freezing periods. These metrics collectively indicated a clear anxiety phenotype relative to control animals that received no DEHP.
Neuroendocrine Modulation by GABA and Testosterone
A subset of DEHP-exposed rats received a GABA agonist 90 minutes before EPM testing, while another subset received testosterone injections every 48 hours for 14 days prior to testing. Both interventions produced the opposite behavioral pattern: increased open-arm exploration, reduced time in enclosed arms, and shorter freezing durations, suggesting that GABAergic signaling and androgen pathways can counteract the anxiety-inducing effects of early DEHP exposure.
Potential Human Relevance
Although the research was performed in rodents, the persistence of anxiety-related changes after a brief developmental exposure to DEHP raises concerns for human health, given the chemical’s ubiquitous presence in everyday products and its documented endocrine activity.
Official Statements & Responses
Dr. Ponzo emphasized that the work demonstrates a lasting behavioral impact of DEHP when exposure occurs during prenatal and immediate post-natal stages, and that the observed neuroendocrine alterations are reversible through pharmacologic activation of GABA receptors or androgen supplementation.
Verbatim Quotes
- “This research demonstrates that one of the most widely used plasticizers worldwide is capable of causing behavioral changes when the subject is exposed during the prenatal and immediate postnatal developmental stages, with this effect lasting over time,” — Osvaldo Juan Ponzo, M.D., Ph.D., Professor of Physiology, University of Buenos Aires School of Medicine
- “This work demonstrates that contact with DEHP in the early stages of life could modify behavior with regard to anxiety, even in the absence of DEHP exposure in adulthood,” — Osvaldo Juan Ponzo
- “These neuroendocrine changes can be reversed by treating with GABA agonists or testosterone.” — Osvaldo Juan Ponzo
Conflicting Reports & Gaps
The study provides no data on female rodents, dose-response relationships, or long-term outcomes beyond the 70-day assessment. Human epidemiological evidence linking early DEHP exposure to anxiety disorders remains absent, highlighting a critical gap for future investigation.
Future Directions
Planned research will examine sex-specific effects, explore lower and higher DEHP dose ranges, and assess the durability of behavioral normalization after cessation of GABA or testosterone treatment. Findings may inform risk-assessment frameworks and regulatory considerations for DEHP use in consumer products.
