Male rats exposed to a widely used plastic chemical during early development showed higher levels of anxiety in adulthood, according to research presented at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
Although the study was conducted in rodents, the findings suggest that exposure to endocrine-disrupting chemicals before and shortly after birth could cause lasting behavioral changes in humans as well.
“This research demonstrates that one of the most used plasticizers worldwide is capable of causing behavioral changes when the subject is exposed during the prenatal and immediate postnatal stages of development, and this effect lasts over time,” said Osvaldo Juan Ponzo, M.D., Ph.D., professor of physiology at the Faculty of Medicine of the University of Buenos Aires in Buenos Aires, Argentina.
Common plastic chemical under investigation
The chemical examined in the study was di-(2-ethylhexyl) phthalate (DEHP), a plasticizer commonly added to products to make them more flexible. It is found in a wide range of items, including medical devices, toys, shower curtains and raincoats.
Previous research has shown that DEHP and the compounds produced when it breaks down can affect various organ systems in both animals and humans, particularly the reproductive and nervous systems. Researchers from the Faculty of Medicine of the University of Buenos Aires set out to investigate whether exposure to DEHP could influence anxiety-related behavior in adult male rats and whether gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, or testosterone played a role in these effects.
Test Anxiety After Early DEHP Exposure
To conduct the study, pregnant female rats received daily oral doses of DEHP from the first day of gestation and continued until their pups were weaned.
Once the male offspring reached adulthood at 70 days of age, the researchers assessed their anxiety-related behavior using an 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 how long they remained motionless, a response known as freezing time.
GABA and testosterone reversed the effects
Ninety minutes before the EPM test, some animals received GABA agonists, molecules that bind to GABA and activate it. Other animals were treated with testosterone every 48 hours for 14 days before testing.
Rats that had been exposed only to DEHP 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 frozen behavior.
In contrast, DEHP-exposed rats receiving GABA or testosterone agonists showed the opposite pattern, suggesting that these treatments counteracted the behavioral effects associated with early DEHP exposure.
“This work demonstrates that contact with DEHP early in life could modify behavior with respect to anxiety, even in the absence of DEHP exposure in adulthood,” Ponzo said. “These neuroendocrine changes can be reversed by treating them with GABA agonists or testosterone.”