Male rats exposed to a widely used plastic chemical during early development showed higher levels of anxiety as adults, 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 potentially cause long lasting behavioral changes in humans as well.
“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,” said Osvaldo Juan Ponzo, M.D., Ph.D., professor of physiology at University of Buenos Aires School of Medicine 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 several organ systems in both animals and humans, particularly the reproductive and nervous systems. Researchers at the University of Buenos Aires School of Medicine 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 those effects.
Testing Anxiety After Early DEHP Exposure
To conduct the study, pregnant female rats received daily oral doses of DEHP beginning on the first day of pregnancy and continuing until their pups were weaned.
Once the male offspring reached adulthood at 70 days of age, 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 enclosed 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 and activate GABA. 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, remained longer in the enclosed arms, and exhibited more freezing behavior.
In contrast, DEHP exposed rats that received either GABA agonists or testosterone showed the opposite pattern, suggesting that these treatments counteracted the behavioral effects associated with early DEHP exposure.
“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,” Ponzo said. “These neuroendocrine changes can be reversed by treating with GABA agonists or testosterone.”