It all adds up
By Tom Dinki, University at Buffalo Department of Chemistry
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The good news: Most of the tested chemicals’ individual
cytotoxicity and neurotoxicity levels were relatively low.
The bad news: The chemicals acted together to make the
entire mixture toxic.
“Though they are structurally similar, not all forever chemicals are made equal — some are more potent, others less. When mixed, all components contributed to the mixture’s cytotoxicity and neurotoxicity,” says the study’s first-author, Karla Ríos-Bonilla, a chemistry PhD student at the University at Buffalo.
“In the laboratory assays we used in this study, most of the
types of PFAS that we tested did not appear to be very toxic when measured
individually. However, when you measure an entire sample with multiple PFAS,
you see the toxicity,” adds study co-author Diana Aga, PhD, director of the
RENEW Institute, SUNY Distinguished Professor and Henry M. Woodburn Chair in
the UB Department of Chemistry.
This research was conducted in collaboration with Beate
Escher of the Helmholtz Centre for Environmental Research (UFZ), Leipzig,
Germany, where Ríos-Bonilla did the in vitro toxicity experiments in the
high-throughput screening facility CITEPro. It was published Sept. 11 in Environmental
Science and Technology, a journal of the American Chemical Society.
The study is novel in that it assesses mixture toxicity of
PFAS. These synthetic compounds have been widely used in consumer products —
from nonstick pans to makeup — for decades, and they can take hundreds to
thousands of years to break down, if ever. They are estimated to be in at least
45% of the nation’s drinking water and in the blood of practically every
American, and they have been linked to cancer and neurodevelopmental disorders.
Earlier this year, U.S. Environmental Protection Agency
(EPA) issued the first-ever drinking water standards for six kinds of PFAS.
However, it is estimated that there are over 15,000 varieties present in the
environment. Only a handful of these chemicals have standards and are
regulated.
“There are six PFAS that can be regulated because we know a
lot about them and their toxicity. Unfortunately, we cannot regulate other
forms of PFAS until their toxicities are known,” says Aga, who is principal
investigator of the EPA STAR grant that funded the research. “We need to set
maximum contamination levels for each PFAS that is proportional to their
toxicity. To regulate contaminants, it is crucial to know their relative
potencies when they occur as mixtures in the environment along with their predicted
environmental concentrations.”
Other co-authors from UB are G. Ekin Atilla-Gokcumen, PhD,
Dr. Marjorie E. Winkler Distinguished Professor and associate chair in the
Department of Chemistry, and Judith Cristobal, PhD, senior research scientist.
Ríos-Bonilla is also supported by a graduate fellowship from
the National Institute of Environmental Health Sciences (NIEHS) of the National
Institutes of Health (NIH).
PFOA and PFOS are major contributors to mixture toxicity
To conduct the study, researchers created their own PFAS
mixtures, one that is representative of an average American’s blood serum, and
the other of surface water samples found in the U.S. Ríos-Bonilla used data
from the U.S. Centers for Disease Control and Prevention and from the U.S.
Geological Survey to determine the average concentration ratios of PFAS in
human blood and in surface water, respectively.
They then tested these mixtures' effects on two cell lines;
one that tests for mitochondrial toxicity and oxidative stress and the other
for neurotoxicity.
Of the 12 PFAS spiked in the water mixture,
perfluorooctanoic acid (PFOA) — commonly used in nonstick pans and firefighting
foam — was the most cytotoxic, making up to 42% of the mixture’s cytotoxicity.
On the other hand, both PFOA and perfluorooctane sulfonic
acid (PFOS) contributed roughly the same cytotoxicity (25%) to the
neurotoxicity assay, despite both contributing only 10 and 15% to the mixture
in terms of concentration, respectively.
The blood mixture had four PFAS present, but PFOA again was
the most cytotoxic to both cell lines. Despite its molar contribution being
only 29%, PFOA triggered 68% of the cytotoxicity in the cytotoxicity assay, and
38% in neurotoxicity assay.
Interestingly, when researchers analyzed the toxicity of the
extracts from real biosolid samples collected from a municipal wastewater
treatment plant, very high toxicities were observed despite the measured low
concentrations of PFOA and other PFAS in the sample.
“This means that there are many more PFAS and other
chemicals in the biosolids, which have not been identified, that contribute to
the toxicity of the extracts observed,” Aga says.
Synergistically versus additive
One of researchers’ goals was to determine if PFAS acts
synergistically. This is when two or more chemicals’ combined effect is greater
than the sum effect of the individual chemicals. However, their findings
indicate that the effect of PFAS is concentration-additive: this means that an
established mixture toxicity prediction model can be used to predict the
combined effect of mixtures.
“As up to 12 PFAS in the mixtures acted
concentration-additive for cytotoxicity and specific neurotoxicity, it is
likely that the thousands of other PFAS that are in commerce and use are also
acting in the same manner,” Escher says. “Mixtures pose more of a risk than
individual PFAS. As they act and occur in mixtures, they ought to be regulated
as mixtures.”
Researchers say the results of this study will also be very
useful in assessing effectiveness of remediation efforts. Breaking down PFAS
can sometimes create harmful byproducts that cannot be detected by chemical
analysis, so measuring the toxicity of a sample after treatment may be the only
way to judge whether a remediation technology is effective.
“Toxicity assays can be a complimentary tool when analytical
chemistry doesn't give you all the answers, especially when the identities of
contaminants in the mixture are unknown, which is the case in many polluted
sites,” Aga says.
