Researchers have long linked perfluoroalkyl and polyfluoroalkyl substances (PFAS), often called “forever chemicals,” to serious birth defects.

However, scientists have struggled to explain exactly how these pollutants affect fetal development. A new study now offers the first detailed molecular explanation, revealing how a PFAS compound known as perfluorodecanoic acid (PFDA) can cause craniofacial abnormalities before birth.

“Most people are exposed to small amounts of PFAS in everyday life, but higher exposure can occur through contaminated water, living near manufacturing sites, or certain jobs like firefighting and ski waxing, which is why it’s so important to understand the chemicals better,” said the paper’s senior author, Jed Lampe, PhD, associate professor at University of Colorado Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences.

“We wanted to understand which PFAS compounds are truly harmful during fetal development, especially for people with higher exposure, and how they cause damage.”

PFDA Identified as the Most Toxic PFAS
Around 15,000 PFAS compounds are used in consumer and industrial products, but growing evidence suggests only a portion of them present major health concerns. To identify the most harmful compounds, Lampe and colleagues Michaela Hvizdak and Sylvie Kandel examined 13 commonly detected PFAS. Their results showed that PFDA was the most toxic to craniofacial development in a fetus.

The researchers found evidence linking PFDA to significant facial abnormalities seen in both people and laboratory animals. Some estimates suggest the compound may increase the risk of these defects by about 10%, even at very low exposure levels.

“This finding moves us beyond association by providing a clear explanation for how PFDA can interfere with fetal development. It’s a critical step toward understanding a vast and complex class of environmental chemicals,” said Lampe.