Researchers have long linked per- and polyfluoroalkyl substances (PFAS)—commonly known as “forever chemicals” to serious birth defects. However, the exact biological mechanisms behind this association remained unclear.
Now, a new study has provided the first clear molecular explanation of how one specific PFAS compound, perfluorodecanoic acid (PFDA), can disrupt fetal development and cause craniofacial abnormalities before birth. The findings were published in the journal Chemical Research in Toxicology.
Understanding PFAS Exposure in Everyday Life
PFAS are a large group of synthetic chemicals widely used in consumer and industrial products, including non-stick cookware, water-resistant fabrics, and firefighting foams. Because these chemicals break down very slowly, they are often referred to as “forever chemicals.”
According to Dr. Jed Lampe, associate professor at the University of Colorado Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences and senior author of the study, most people encounter low levels of PFAS exposure in daily life.
However, certain groups face higher exposure risks, particularly individuals who live near manufacturing sites or work in occupations such as firefighting or ski waxing, where PFAS-containing products are frequently used.
“We wanted to understand which PFAS compounds are truly harmful during fetal development and how they cause damage,” Dr. Lampe explained.
Scientists Identify PFDA as a Highly Toxic PFAS Compound
Although scientists estimate that around 15,000 PFAS compounds exist, research suggests that only a subset may pose serious health risks.
In the study, researchers tested 139 commonly detected PFAS chemicals to assess their effects on fetal craniofacial development. Through these experiments, the team identified PFDA as the most toxic compound in this context.
Importantly, the researchers found that even extremely low levels of PFDA exposure could cause visible facial abnormalities in developing embryos. Furthermore, the risk of defects increased by about 10% even at minimal exposure levels.
“This finding moves us beyond simple association,” Dr. Lampe noted. “It provides a clear biological explanation for how PFDA interferes with fetal development.”
PFDA Disrupts a Critical Developmental Hormone
As reported by medicalxpress, the study revealed that PFDA interferes with retinoic acid, a molecule that plays a crucial role in shaping the face and head during early pregnancy.
Retinoic acid regulates hundreds of genes involved in embryonic development, and its levels must remain tightly controlled. Unlike adults, a developing fetus cannot produce or safely eliminate excess retinoic acid. Instead, it relies on the mother’s body to maintain the correct balance of the hormone.
However, PFDA disrupts this delicate system.
Blocking a Key Enzyme That Regulates Retinoic Acid
Researchers discovered that PFDA blocks CYP26A1, a key enzyme responsible for breaking down excess retinoic acid.
When this enzyme is inhibited, retinoic acid accumulates to harmful levels, which can interfere with normal facial development in the fetus. Additionally, PFDA suppresses the genes responsible for producing CYP26A1, creating a “double-hit” effect that further disrupts the regulatory system.
As a result, abnormal levels of retinoic acid can lead to severe craniofacial defects, including underdeveloped eyes and abnormal jaw formation.
“These were the most common abnormalities we observed during PFDA exposure in fetal development,” Dr. Lampe explained.
Findings Could Improve Chemical Risk Assessment
The researchers believe that identifying the molecular mechanism behind PFDA toxicity represents a major step forward in understanding the health risks of PFAS.
By clarifying how these chemicals affect fetal development, scientists can now work toward developing targeted laboratory tests and computer-based screening tools. These tools could help researchers rapidly evaluate thousands of PFAS compounds and rank them according to potential risk.
Supporting Safer Chemical Design and Public Health Protection
Ultimately, the researchers hope their findings will help regulators and manufacturers distinguish harmful PFAS from safer alternatives. This knowledge could guide the development of less toxic industrial chemicals in the future.
In addition, the study may help identify protective strategies for individuals with higher occupational exposure, including firefighters and ski wax technicians.
Future research could explore ways to reduce PFDA exposure during pregnancy or develop interventions that protect fetal development, thereby lowering the risk of environmentally linked birth defects.