Forever Chemicals, Real Impacts: Insights from ISPE Boston’s PFAS Session

The ISPE Boston Area Chapter was happy to host last month’s event: “PFAS: Understanding ‘Forever Chemicals’ and their potential impacts on pharmaceutical manufacturing”. The event was very informative, and the question-and-answer session postponed the end time by 45 minutes.  Our speakers provided an informative session and left everyone in attendance with a greater understanding of the threat PFAS pose and insight into a framework for navigating the impact of these chemicals on a process. Newsworthy developments on per- and polyfluoroalkyl substances (PFAS) mirror some of the issues raised at our recent event.

In New York, lawmakers proposed a 5-year moratorium on using sewage sludge as fertilizer on farmland due to PFAS contamination risks, which have been linked to health issues like cancer and reproductive problems. The bill also aims to establish a biosolids task force and a PFAS agricultural response program. Read more about this at this link: https://spectrumlocalnews.com/nys/capital-region/sewage-sludge/2025/04/30/new-york-proposes-5-year-moratorium-on-sludge-on-farmland

In South Dakota, the state allocated $250,000 to clean up PFAS from fire departments and schools, targeting items like firefighting foam and lab chemicals for safe disposal. Additionally, a bill was passed requiring firefighting gear to be labeled for PFAS content to promote safer alternatives. Read more about this here: https://www.yahoo.com/news/state-offering-free-pfas-cleanup-175634

One main PFAS source is Aqueous Film-Forming Foam (AFFF), a type of firefighting foam historically used to extinguish flammable liquid fires. This report here: https://media.defense.gov/2022/Apr/05/2002970013/-1/-1/0/AFFF-TECHNOLOGIES-REPLACEMENT-AND-ALTERNATIVES-BRIEFING-FEB-2022.PDF lists several alternatives to AFFF.

Another item mentioned in the meeting was the metabolic pathway of PFAS. Dr. Pennoyer identified that these chemicals are readily absorbed but have significantly long half-lives. The Toxicological Profile for Perfluoroalkyls here, https://www.atsdr.cdc.gov/toxprofiles/tp200.pdf, contains some interesting insights about the potential toxicity mechanisms of these compounds. One pathway to explain health effects is that perfluoroalkyl may activate the nuclear receptor peroxisome proliferator-activated receptor-α (PPARα). Its activation is linked to liver toxicity, reduced cholesterol levels, and developmental delays in exposed lab animals. PPARα, a transcription factor, regulates lipid metabolism, cell growth, and differentiation. PFOS exposure alters gene expression in the PPARα pathway, leading to peroxisome proliferation in rodent livers, causing cholesterol accumulation, hepatocyte vacuolization, hyperproliferation, and liver enlargement. Further research is needed to understand serum cholesterol effects in livestock and companion animals.

PPARα is also critical in rodent and human embryos. Its activation during gestation is associated with lower postnatal survival, delayed eye opening, reduced pup survival, and lower body weights, potentially due to lipid metabolism disruption. PFAS exposure suppresses T-cell-dependent antibody responses and antigen-specific IgM titers in vitro studies.

PFAS are linked to altered thyroid function in humans and animals, with varying mechanisms and outcomes across species. The 2021 ATSDR PFAS toxicological profile noted mixed findings: some studies show positive associations with hypothyroidism, others with hyperthyroidism, and some show no link. No association with thyroid function has been established in dogs. These metabolic effects echo the associations between perfluoroalkyl exposure and documented health outcomes in human populations.

Thank you to our sponsors who make these programs possible:

Arcadis

Burkert

DECCO

DC Beane and Associates