A Probabilistic Approach to Evaluate the Risk of Decreased Total Triiodothyronine Hormone Levels following Chronic Exposure to PFOS and PFHxS via Contaminated Drinking Water

Abstract

BACKGROUND: Extensive exposure to per-and polyfluoroalkyl substances (PFAS) have been observed in many countries. Current deterministic frameworks for risk assessment lack the ability to predict the likelihood of effects and to assess uncertainty. When exposure exceeds tolerable intake levels, these shortcomings hamper risk management and communication. OBJECTIVE: The integrated probabilistic risk assessment (IPRA) combines dose-response and exposure data to estimate the likelihood of adverse effects. We evaluated the usefulness of the IPRA for risk characterization related to decreased levels of total triiodothyronine (T 3) in humans following a real case of high exposure to PFAS via drinking water. METHODS: PFAS exposure was defined as serum levels from residents of a contaminated area in Ronneby, Sweden. Median levels were 270 ng=mL [perfluorooctane sulfonic acid (PFOS)] and 229 ng=mL [perfluorohexane sulfonic acid (PFHxS)] for individuals who resided in Ronneby 1 y before the exposure termination. This data was integrated with data from a subchronic toxicity study in monkeys exposed daily to PFOS. Benchmark dose modeling was employed to describe separate dose-effect relationship for males and females, and extrapolation factor distributions were used to estimate the corresponding human benchmark dose. The critical effect level was defined as a 10% decrease in total T 3. RESULTS: The median probability of critical exposure, following a combined exposure to PFOS and PFHxS, was estimated to be [2.1% (90% CI: 0:4%-13:1%)]. Gender-based analysis showed that this risk was almost entirely distributed among women, namely [3.9% (90% CI: 0:8%-21:6%)]. DISCUSSION: The IPRA was compared with the traditional deterministic Margin of Exposure (MoE) approach. We conclude that probabilistic risk characterization represents an important step forward in the ability to adequately analyze group-specific health risks. Moreover, quantifying the sources of uncertainty is desirable, as it improves the awareness among stakeholders and will guide future efforts to improve accuracy.

Plasma, liver, and kidney exposures in rats after oral doses of industrial chemicals predicted using physiologically based pharmacokinetic models: A case study of perfluorooctane sulfonic acid

“…The levels of the repeated virtual doses of perfluorooctane sulfonic acid (0.041 and 0.16 µg/kg/day) for 90 days in humans were calculated via reverse dosimetry using the 50th and 95th percentiles of human blood levels from 2015-2016 (0.0048 and 0.0183 ng/mL), respectively, published in a biomon-itoring report from the USA (Fourth National Report on Human Exposure to Environmental Chemicals Updated Tables, January 2019, https://www.cdc.gov/exposurereport/). These 50th and 95th percentile concentrations in the blood potentially imply exposures roughly similar to the reference dose (0.02 μg/kg/day) with an uncertainty factor of 30 recommended by regulatory authorities (Silva et al, 2020). In-depth forward and reverse assessment of perfluorooctane sulfonic acid levels could be facilitated by adopting the current human PBPK model.…”

“…These compounds are of particular interest because measurable blood levels are detected in the general population worldwide (Lau et al, 2007;Wambaugh et al, 2013). Because extensive exposure to perfluoroalkyl substances has been observed in many countries (Silva et al, 2020), a multicompartment pharmacokinetic model was set up for perfluorinated compounds to facilitate integrated probabilistic risk assessment (Wambaugh et al, 2013). In this study, we investigated tissue concentrations of perfluorooctane sulfonic acid as a model perfluoroalkyl compound ( Fig.…”

Impact of the Sediment Organic vs. Mineral Content on Distribution of the Per- and Polyfluoroalkyl Substances (PFAS) in Lake Sediment

“…In present study, the investigated area represents the case of severe drinking water contamination, with over 16,000 individuals exposed among the population between the 1980s and 2013 [ 17 , 18 ]. The health-related risks have been under extensive investigation, including the assessment of exposure conditions and associated PFAS levels in human serum [ 13 , 19 ]. A better understanding of the PFAS distribution in the area was needed.…”

“…The retrospective estimates on contamination levels in drinking water are important for the human exposure investigation, in particular for the dose–response relationships [ 14 , 19 ]. PFAS mass balance and transport have been studied for surface water [ 20 , 21 ], groundwater [ 14 , 22 ] and water treatment plants [ 23 , 24 ].…”

In vitro toxicity assessment of paints with antimicrobial properties - a comparative study

“…The commonly used approach of comparing the estimated exposures (in this case serum levels) to a guidance value estimated to be without appreciable health effects played a major role in the court case. An alternative to this deterministic assessment is probabilistic risk assessment [2] . We argue that this would be particularly useful in situations like the Ronneby case, when a deterministic (point estimates) risk assessment indicates that guidance values are exceeded or when significant equity or environmental justice issues are raised by interindividual variability.…”