Toxicity unclear

Worrying Wilmington residents and public health officials is that scientists don’t know whether or how drinking water tainted with GenX-related chemicals has affected or might affect people’s health.

To provide guidance on drinking water safety, the North Carolina Department of Health & Human Services turned to the European Chemicals Agency, one of the few sources of toxicity data for GenX. DuPont registered the compound for manufacture and use in the European Union under the Registration, Evaluation, Authorisation & Restriction of Chemicals law, or REACH. Data that DuPont submitted to the EU agency to support that registration included results of a two-year chronic toxicity and carcinogenicity study in laboratory rats. Using this information, the EU agency determined that ingesting 1 mg of GenX per kg of body weight perday would have no observable adverse effects.

After consulting with EPA, North Carolina in July set a public health goal of 140 ppt for HFPO-DA in drinking water, based on the information from the European Agency. A public health goal is the level of pollution below which no adverse health effects would be expected over a lifetime of exposure. It is a metric used for guidance only.

Although GenX—or, specifically, the HFPO-DA anion—has gotten the most attention, “I’m not sure whether it’s the most toxic in the mix of chemicals we’ve found,” Knappe says. He is particularly concerned about two by-products of Nafion manufacture that Strynar’s team found in the river. These are longer-chain fluorochemicals than HFPO-DA and are likely more bioaccumulative than the GenX-related compounds, Knappe says. Given the comments by Chemours’s O’Keefe, Knappe wonders whether the plant might have discharged Nafion by-products into the Cape Fear River for decades, just as it released the HFPO-DA and related chemicals produced in the manufacture of vinyl ethers.

HFPO-DA, GenX, and related compounds; the Nafion by-products; and various other per- and polyfluoroalkyl substances are collectively called PFASs. For its part, EPA says that exposure to PFASs can cause a number of adverse health effects, on the basis of laboratory studies that exposed monkeys, rats, and mice to PFOA or PFOS. Some studies in humans show that certain PFASs may harm the development of fetuses and children, interfere with hormones and decrease fertility, raise cholesterol levels, hamper the immune system, and increase a person’s chance of developing cancer, EPA says.

Nevertheless, EPA currently has no national regulation or guidance for GenX-related compounds in drinking water. In December, however, EPA announced that a panel of scientists from across the agency is addressing PFASs. That group is bringing together scientists from EPA’s water and research programs as well as its air, chemicals, and waste offices, the agency says. EPA says it will work closely with states and tribes on PFAS pollution.

Chinese researchers have also raised flags about these chemicals. Results of cellular and protein assays of liver function suggest that HFPO-related chemicals and other substitutes for PFOA and PFOS could cause greater liver toxicity than the compounds they’re replacing, says a study led by Jiayin Dai, who heads an ecotoxicology group at the Chinese Academy of Sciences’ Key Laboratory of Animal Ecology & Conservation Biology. The researchers found that replacing hydrogen with fluorine might reduce toxicity, but inserting oxygen atoms and increasing chain length “seem to be able to induce more serious toxicities,” the study says (Arch. Toxicol. 2017, DOI:10.1007/s00204-017-2055-1).

And a study published by researchers in Sweden at the end of January concludes that GenX is more toxic than PFOA, on the basis of a computer model that analyzed data from studies in laboratory rats. When differences in the rates of distribution and elimination of these chemicals in the body are accounted for, the study says, “some fluorinated alternatives have similar or higher toxic potency than their predecessors.” (Environ. Int., 2018, DOI: 10.1016/j.envint.2018.01.011).

A two-year, $275,000 grant awarded late last year to NC State researchers by the U.S. National Institute of Environmental Health Sciences should reveal more about these compounds’ toxicity in humans. Principal investigator Jane Hoppin, an epidemiologist and deputy director of NC State’s Center for Human Health & the Environment, says the work involves studying the blood and urine of 300 residents of the Wilmington area whose tap water is supplied by the local water company, the Cape Fear Public Utility Authority, for the presence of HFPO-DA anion, the two Nafion by-products, and a suite of other polyfluorinated substances.

These chemicals have never been measured in people before, Hoppin tells C&EN. Researchers will be looking at the quantity of PFASs people have in their bodies as well as their lipid levels and thyroid and liver functions, she says. Previous epidemiology studies with other PFASs found effects in these metabolic measures that were linked to exposure.

A key issue researchers hope to answer in the North Carolina study is how long these substances remain in people’s bodies, Hoppin says. Nothing is known about the half-life of GenX-related compounds in humans, she explains. She expects to have initial results from the study in late February, although publication will take longer.

In October, lawyers for people who drank the contaminated water in North Carolina filed a class-action suit against Chemours and DowDuPont. The plaintiffs want the companies to provide monitoring for health problems that may be caused by the fluorinated compounds they ingested.