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A probabilistic approach to evaluate the risk of decreased total triiodothyronine hormone levels following chronic exposure to PFOS and PFHxS via contaminated drinking water

Silva, Antero Vieira ; Ringblom, Joakim ; Lindh, Christian LU orcid ; Scott, Kristin LU ; Jakobsson, Kristina LU and Öberg, Mattias (2020) In Environmental Health Perspectives 128(7). p.1-11
Abstract

BACKGROUND: Extensive exposure to per-and polyfluoroalkyl substances (PFAS) have been observed in many countries. Current deterministic frame-works 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 (T3) in humans following a real case of high exposure to PFAS via drinking water. METHODS: PFAS... (More)

BACKGROUND: Extensive exposure to per-and polyfluoroalkyl substances (PFAS) have been observed in many countries. Current deterministic frame-works 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 (T3) 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 T3. 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 sour-ces of uncertainty is desirable, as it improves the awareness among stakeholders and will guide future efforts to improve accuracy. https://doi.org/10.1289/EHP6654.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Environmental Health Perspectives
volume
128
issue
7
article number
076001
pages
11 pages
publisher
National Institute of Environmental Health Sciences
external identifiers
  • pmid:32639173
  • scopus:85088209447
ISSN
0091-6765
DOI
10.1289/EHP6654
language
English
LU publication?
yes
id
2af93f2a-532d-4ad4-993f-ed339f9d3f66
date added to LUP
2021-01-04 14:18:20
date last changed
2024-04-17 22:26:24
@article{2af93f2a-532d-4ad4-993f-ed339f9d3f66,
  abstract     = {{<p>BACKGROUND: Extensive exposure to per-and polyfluoroalkyl substances (PFAS) have been observed in many countries. Current deterministic frame-works 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. O<sub>BJECTIVE</sub>: 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<sub>3</sub>) 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<sub>3</sub>. 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 sour-ces of uncertainty is desirable, as it improves the awareness among stakeholders and will guide future efforts to improve accuracy. https://doi.org/10.1289/EHP6654.</p>}},
  author       = {{Silva, Antero Vieira and Ringblom, Joakim and Lindh, Christian and Scott, Kristin and Jakobsson, Kristina and Öberg, Mattias}},
  issn         = {{0091-6765}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1--11}},
  publisher    = {{National Institute of Environmental Health Sciences}},
  series       = {{Environmental Health Perspectives}},
  title        = {{A probabilistic approach to evaluate the risk of decreased total triiodothyronine hormone levels following chronic exposure to PFOS and PFHxS via contaminated drinking water}},
  url          = {{http://dx.doi.org/10.1289/EHP6654}},
  doi          = {{10.1289/EHP6654}},
  volume       = {{128}},
  year         = {{2020}},
}