One ‘Forever Chemical’ Found In Millions Of Homes May Disrupt A Baby’s Facial Development

Sofas. Carpets. Stain-resistant clothing. Many of the products filling American homes contain PFDA, a synthetic chemical that new research links to a disruption in a key vitamin A pathway involved in fetal development.

Researchers at the University of Colorado have pinpointed a potential mechanism through which PFDA may interfere with a maternal liver enzyme that keeps vitamin A in careful balance during pregnancy. Disruptions to that balance have been linked in prior research to facial birth defects including cleft palate, malformed eyes, and missing nasal structures. Findings were published in Chemical Research in Toxicology.

Craniofacial abnormalities account for roughly one in three congenital birth defects worldwide, and scientists have long suspected PFAS exposure during pregnancy contributes to them. What has been missing is a clear biological explanation for how. This study, conducted in isolated enzymes and human liver cell cultures, takes a meaningful step toward proposing one.

PFAS in American Homes and American Blood

PFDA, short for perfluorodecanoic acid, belongs to a family of nearly 15,000 synthetic compounds engineered to repel heat, water, and stains. These compounds, collectively known as PFAS or “forever chemicals,” are notorious for one thing above all else: they don’t break down. Not in the environment, and not in the human body. An estimated 98% of Americans carry detectable PFAS in their blood, and PFAS compounds like PFDA have historically been used in stain- and grease-resistant coatings on textiles, furniture, and carpeting.

Once PFDA enters the body, it sticks around. According to the paper, the compound’s estimated biological half-life in human serum is roughly 12 years. A process in which the compound continuously cycles between the liver and intestines may concentrate it in liver tissue at levels above what a standard blood test would indicate, a detail that becomes relevant when considering what this chemical does once it gets there.

How PFDA May Interfere With a Critical Pregnancy Enzyme

During pregnancy, a liver enzyme called CYP26A1 quietly performs one of the most consequential jobs in fetal development. Its function is to break down excess retinoic acid, a biologically active form of vitamin A, and keep maternal blood levels within a precise, narrow range. Retinoic acid directs the activity of more than 500 genes involved in building the fetal face, eyes, skull, and nervous system. Too much of it is just as dangerous as too little, and since the fetal liver is not equipped to manage this on its own, the mother’s liver does the work for both.

When researchers screened 13 PFAS compounds for their ability to disrupt this enzyme, PFDA stood out clearly. At high concentrations tested in the lab, it reduced CYP26A1 activity by over 93 percent. Nothing else in the group came close.

PFDA’s potency appears to come down to structure. It is shaped much like retinoic acid, with a similar long chain and a similar chemical tip. Computer modeling showed the two molecules occupy the same slot in the enzyme’s active site, meaning PFDA can take retinoic acid’s place and block the breakdown process, all without being processed itself. In other words, the body’s cleanup crew may be mistaking a forever chemical for the very thing it is supposed to remove.

What Happened When Human Liver Cells Were Exposed

To see whether these results would hold up in something closer to a real biological system, researchers exposed human liver cells from female donors aged 16 to 40 to increasing concentrations of PFDA over 48 hours. Cells were first conditioned with retinoic acid at the levels typically found in a pregnant woman’s blood.

At the highest dose that did not damage the cells outright, retinoic acid clearance dropped by roughly 78 to 88 percent compared to controls, and retinoic acid levels in the cells climbed substantially above normal. Gene analysis of the treated cells showed disrupted activity across pathways involved in vitamin A metabolism and in genes specifically tied to the development of the fetal face and skeleton.

It bears emphasizing that the concentrations used in the lab were considerably higher than what most people carry in their blood. Researchers acknowledge this gap but argue that PFDA’s 12-year estimated half-life and its repeated cycling through the liver could push concentrations into a more relevant range in heavily exposed individuals. That remains an open question.

A Pattern That Has Followed PFAS for Decades

Suspicions about PFDA and birth defects are not new. Internal DuPont surveillance from the late 1970s documented two children born to factory workers with craniofacial abnormalities including malformed or missing eyes and nostrils, among the first recorded hints that PFAS might cause birth defects. The authors also point to prior studies suggesting PFDA in maternal blood was the most strongly associated of six prominent PFAS with subtle narrowing of eye-opening width, a recognized marker of disrupted facial development, in children at age five. Additional research they reference, involving a screening of 139 PFAS compounds in zebrafish, identified PFDA as the most developmentally toxic of the group.

Each of those findings pointed toward a problem without explaining what was driving it. By showing how PFDA may block the enzyme responsible for keeping vitamin A levels in check, and how that disruption ripples into gene-level effects, this research offers a possible molecular explanation for a pattern that has persisted in the scientific literature for decades.

PFDA remains in American homes and bloodstreams despite the phase-out of related legacy compounds. In-vivo studies are still needed to confirm that what happens in cell cultures translates to living organisms. But for expecting families and regulators alike, the mechanism identified here is one worth watching closely.

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Disclaimer: This article is based on laboratory research conducted in isolated enzymes and human liver cell cultures. Findings have not been confirmed in living humans or animals and should not be interpreted as proof that PFDA causes birth defects. The study identifies a potential biological mechanism that warrants further investigation.

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