Trending Clinical Topic: Forever Chemicals

Ryan Syrek


August 26, 2022

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Per- and polyfluoroalkyl substances (PFAS), commonly known as "forever chemicals," have been linked to a slew of health concerns. These include cancer, fertility and pregnancy issues, developmental problems in children, immunodeficiency, and heart-related conditions. Although manufacturers have begun phasing them out, their continued presence is a concern. Recent findings clarifying the nature of their threat and where they can now be found resulted in this week's top trending clinical topic (see Infographic).

PFAS have been used in various products from food packaging to waterproof clothing. Researchers have now found major environmental contamination in the atmosphere, including in rainwater, snow, soil, and even human blood. Over the past 20 years, countries around the world decreased their recommended limits for PFAS in water and soil as health impacts became clearer. In the United States, recommendations for perfluorooctanoic acid (PFOA) levels dropped from 70 parts per trillion to .004 part per trillion, a factor of 37.5 million. Researchers found PFOA levels in drinking water exceed these guidelines in every part of the world, even in some of the most remote areas such as Antarctica and the Tibetan plateau. "Based on the latest U.S. guidelines for [perfluorooctanoic acid] in drinking water, rainwater everywhere would be judged unsafe to drink," Ian Cousins, PhD, the lead study author, said in a statement.

Among the newly clarified health concerns, a recent study found that ingestion of forever chemicals may be a modifiable risk factor for the development of hypertension. In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk for hypertension in middle-aged women. The study examined the association between serum concentrations of PFAS and risk for incident hypertension in 1058 initially normotensive women. Women in the highest tertile of overall PFAS concentration had a 71% increased risk of developing hypertension (adjusted hazard ratio [aHR], 1.71; 95% CI, 1.15-2.54; P trend = .008). Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension compared with those in the lowest tertile (aHR, 1.42; 95% CI, 1.19-1.68; P trend = .01). The risks persisted after adjustment for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

Diabetes is also a concern for women when it comes to forever chemicals. New research shows that "given that 1.5 million Americans are newly diagnosed with diabetes each year in the USA, approximately 370,000 new cases of diabetes annually in the US are attributable to PFAS exposure." The findings come from a prospective study of 1237 women, with a median age of 49.4 years. Over the study period, 102 cases of incident diabetes were noted, representing a rate of 6 cases per 1000 person-years. After adjustment for key confounders, those in the highest tertile of exposure to a combination of all seven of the PFAS were significantly more likely to develop diabetes compared with those in the lowest tertile for exposure (hazard ratio [HR], 2.62). This risk was greater than that seen with individual PFASs (HR, 1.36-1.85), suggesting a potential additive or synergistic effect of multiple PFASs on diabetes risk. The association between the combined exposure to PFASs among the highest vs lowest tertile was similar to the risk for diabetes developing among those who were overweight (BMI 25 to < 30) vs normal weight (HR, 2.89) and higher than the risk among current vs never-smokers (HR, 2.30).

Another recent study found that PFAS exposure may also lead to liver damage and could be a culprit in rising rates of nonalcoholic fatty liver disease (NAFLD). Researchers found "consistent" evidence for hepatotoxicity from rodent studies, and exposure to PFAS was associated with liver function markers in observational studies in humans. The review included 85 rodent studies and 24 epidemiologic studies, primarily involving people from the United States. Meta-analyses of human studies found that higher levels of alanine aminotransferase were significantly associated with exposure to PFOA, PFOS, and perfluorononanoic acid (PFNA). Exposure to PFOA was also associated with higher aspartate aminotransferase and gamma-glutamyltransferase levels in humans. The "positive" and "convincing" associations between exposure to forever chemicals and these liver markers suggest that exposure may contribute to the growing NAFLD epidemic, according to the researchers.

The wealth of evidence linking forever chemicals to adverse health effects certainly prompted changes in manufacturing. However, the fallout from their creation continues to be a major concern. As more studies clarify specific risks, interest is likely to surge again, as it did this week.

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