Male rats exposed to the plasticizer di-(2-ethylhexyl) phthalate (DEHP) during early development showed increased anxiety-related behaviors as adults, according to research presented at ENDO 2026, the Endocrine Society's annual meeting in Chicago, Ill., on June 14.
The study, conducted by scientists at the University of Buenos Aires School of Medicine, aimed to assess whether exposure to DEHP—a chemical commonly used in products like medical devices and toys—during gestation and early life could lead to long-term behavioral changes. Researchers also sought to determine if these effects were linked to the neurotransmitter gamma-aminobutyric acid (GABA) or testosterone levels.
Pregnant female rats received daily oral doses of DEHP from the first day of gestation until their litters were weaned. Once male offspring reached maturity at 70 days old, they underwent behavioral testing using an elevated plus maze (EPM), which measures rodents' aversion to open spaces and heights. The researchers recorded how often and how long each rat spent in open versus closed arms of the maze, as well as periods of immobility known as freezing time.
Some animals received GABA agonists ninety minutes before EPM testing, while others were treated with testosterone every 48 hours for two weeks prior. Results indicated that rats exposed only to DEHP spent less time exploring open arms and more time in closed arms compared with other groups. These rats also exhibited longer freezing times. However, treatment with GABA agonists or testosterone appeared to reverse these anxiety-like behaviors.
"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."
