Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China

Nian, Min; Li, Qing Qing; Bloom, Michael S.; Qian, Zhengmin; Syberg, Kevin M; Vaughn, Michael G.; Wang, Si Quan; Wei, Qi; Zeeshan, Mohammed; Gurram, Namratha; Chu, Chu; Wang, Jia; Tian, Yuan; Hu, Li; Liu, Kang Kang; Yang, Bo; Liu, Ru Qing; Feng, Dan; Zeng, Xiao Wen; Dong, Guang‐Hui

doi:10.1016/j.envres.2019.02.013

Cited by 65 publications

(25 citation statements)

References 54 publications

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“…In parallel to cholesterol changes, an increased incidence of mildly elevated serum levels of the liver enzyme alanine transferase (ALT) associated with PFOA exposure was recorded (Lin et al 2010;Gallo et al 2012;Darrow et al 2013;Gleason et al 2015;Salihovic et al 2018;Jain and Ducatman 2019;Nian et al 2019). Some studies reported similar findings for PFOS (Lin et al 2010;Gallo et al 2012;Salihovic et al 2018).…”

Section: Effects Observed In Human Studiesmentioning

confidence: 92%

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Fragki

Dirven

Fletcher

et al. 2021

Critical Reviews in Toxicology

102

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Associations between per-and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans. This paper aims to present the main issues regarding the modulation of lipid homeostasis by the two most common PFASs, PFOS and PFOA, with emphasis on the underlying mechanisms relevant for humans. Overall, the apparent contrast between human and animal data may be an artifact of dose, with different molecular pathways coming into play upon exposure to PFASs at very low versus high levels. Altogether, the interpretation of existing rodent data on PFOS/PFOA-induced lipid perturbations with respect to the human situation is complex. From a mechanistic perspective, research on human liver cells shows that PFOS/PFOA activate the PPARa pathway, whereas studies on the involvement of other nuclear receptors, like PXR, are less conclusive. Other data indicate that suppression of the nuclear receptor HNF4a signaling pathway, as well as perturbations of bile acid metabolism and transport might be important cellular events that require further investigation. Future studies with human-relevant test systems would help to obtain more insight into the mechanistic pathways pertinent for humans. These studies shall be designed with a careful consideration of appropriate dosing and toxicokinetics, so as to enable biologically plausible quantitative extrapolations. Such research will increase the understanding of possible perturbed lipid homeostasis related to PFOS/ PFOA exposure and the potential implications for human health.

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Section: Effects Observed In Human Studiesmentioning

confidence: 92%

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Fragki

Dirven

Fletcher

et al. 2021

Critical Reviews in Toxicology

102

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“…Nian et al. () reported cross‐sectional findings regarding associations between PFOS/PFOA and liver biomarkers in 1605 adult government employees or residents in Shenyang, China (see also Bao et al., ). The median PFOS and PFOA concentrations in serum were 24 and 6.2 ng/mL.…”

Section: Assessmentmentioning

confidence: 99%

“…For ALT, there was a statistically significant association between the change of PFOS/PFOA and the change of serum ALT. Nian et al (2019) reported cross-sectional findings regarding associations between PFOS/PFOA and liver biomarkers in 1605 adult government employees or residents in Shenyang, China (see also Bao et al, 2017). The median PFOS and PFOA concentrations in serum were 24 and 6.2 ng/mL.…”

Section: Pfos and Pfoamentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

307

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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“…Studies have shown that exposure to PFAS is associated with a variety of adverse health outcomes in humans, including hypertension, low birth weight, liver problems, thyroid problems, decreased vaccine response in children, and higher incidence of several kinds of cancer (Agency for Toxic Substances and Disease Registry (ATSDR), 2018; Grandjean et al, 2012;Granum et al, 2013;Kim et al, 2018;Nian et al, 2019;X. W. Zeng et al, 2019;.…”

Section: Introductionmentioning

confidence: 99%

Linking Industrial Point Sources to PFAS Contamination in Wells: Michigan Case Study

Schulz

Filbin

Silva

et al. 2021

Preprint

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In recent years, concern has grown over widespread environmental contamination of per- and polyfluoroalkyl substances (PFAS) in the environment and especially in drinking water. These manmade chemicals were first synthesized in the mid-20th century and contain thousands of individual species, some of which are still used today. A wide variety of industries use or have historically used PFAS in their products and processes. PFAS chemicals are recalcitrant by design and thus do not break down in the environment. Federal and state agencies have begun testing of drinking water and other media for PFAS in order to understand the extent of contamination and determine any necessary regulatory actions. Testing is expensive, however, and it would be beneficial to be able to prioritize wells for testing based on their likely vulnerability. This study presents a methodology for identifying locations of industrial sites likely to use PFAS, and uses Michigan’s robust well testing data alongside industry and environmental factors to identify any spatial relationships that can be used to help prioritize testing of wells.

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Liver function biomarkers disorder is associated with exposure to perfluoroalkyl acids in adults: Isomers of C8 Health Project in China

Cited by 65 publications

References 54 publications

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Risk to human health related to the presence of perfluoroalkyl substances in food

Linking Industrial Point Sources to PFAS Contamination in Wells: Michigan Case Study

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