Male rats exposed to widely used plastic chemicals during early development showed higher levels of anxiety as adults, according to a study presented at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
Although the study was conducted in rodents, the findings suggest that prenatal and immediate exposure to endocrine disruptors can also cause long-term behavioral changes in humans.
“This study shows that one of the most widely used plasticizers in the world can induce behavioral changes when exposed to subjects during prenatal and early postnatal development, and that this effect persists over long periods of time,” said Osvaldo Juan Ponzo, MD, professor of physiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Common plastic chemicals under research
The chemical investigated in this study is di-(2-ethylhexyl) phthalate (DEHP), a plasticizer commonly added to products to increase their flexibility. Used in a wide range of items including medical equipment, toys, shower curtains, and raincoats.
Previous studies have shown that DEHP and the compounds produced during its breakdown can affect several organ systems in both animals and humans, particularly the reproductive and nervous systems. Researchers at the University of Buenos Aires School of Medicine began investigating whether exposure to DEHP affects anxiety-related behaviors in adult male rats, and whether the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and testosterone are involved in these effects.
Testing for anxiety after initial DEHP exposure
To conduct the study, pregnant female rats were orally administered DEHP daily starting from the first day of pregnancy until the pups were weaned.
Once the male offspring reached adulthood at 70 days of age, the researchers assessed anxiety-related behaviors using the elevated plus maze (EPM). This test takes advantage of rodents’ natural tendency to avoid heights and open areas. The maze is shaped like a plus sign and contains two open arms and two closed arms.
The researchers measured how often the rats entered each type of arm, how much time they spent there, and a response known as resting time.
GABA and testosterone reverse the effects
Ninety minutes before the EPM test, some animals were given a GABA agonist, a molecule that binds to and activates GABA. Other animals received testosterone every 48 hours for 14 days prior to testing.
Rats exposed to DEHP alone showed clear signs of increased anxiety. They spent less time exploring the open arms of the maze, stayed longer in the closed arms, and exhibited more freezing behavior.
In contrast, DEHP-exposed rats administered either GABA agonists or testosterone showed the opposite pattern, suggesting that these treatments counteract the behavioral effects associated with initial DEHP exposure.
“This study shows that exposure to DEHP early in life can change anxiety-related behaviors, even if you are not exposed to it in adulthood,” Ponzo said. “These neuroendocrine changes can be reversed by treatment with GABA agonists or testosterone.”
