Climatic conditions and concentrations of BTEX compounds in atmospheric media.

Climatic and meteorological conditions are among the factors affecting the ambient concentrations of BTEX compounds. This systematic review and meta-analysis aimed to interrogate the seasonal effect of climatic conditions on the concentrations of BTEX compounds. Three electronic bibliographic databases including Scopus, PubMed, and Web of Science were systematically searched up to November 14, 2023. The search algorithm followed PRISMA guidance and consisted of three groupings of keywords and their possible combinations. For various climatic conditions, the overall mean and 95% confidence interval (CI) of effect size related to BTEX concentrations were calculated using a random-effect model. In total, 104 articles were included for evaluation in this review. BTEX ambient concentration was higher in winter (ranging from 36 out of 79 relevant studies for xylene to 52 out of 97 relevant studies for benzene) followed by summer and autumn. For humidity conditions, the highest exposure values for BTEX were detected for rainy weather (ranging from 3 out of 5 relevant studies for toluene and xylene to 4 out of 5 relevant studies for benzene and ethyl benzene) compared to dry conditions. The pooled concentration (µg/m3) of benzene, toluene, ethyl benzene, and xylene were computed as 2.61, 7.12, 2.21, and 3.61 in spring, 2.13, 7.53, 1.61, and 2.75 in summer, 3.04, 9.59, 3.14, and 5.50 in autumn, and 3.56, 8.71, 2.35, and 3.91 in winter, respectively. Moreover, the pooled concentrations (µg/m3) of BTEX were measured as 2.98, 7.22, 1.90, and 3.03 in dry weather and 3.15, 6.30, 2.14, and 3.86 in rainy or wet weather, respectively. In most seasons, the ambient concentrations of BTEX were higher in countries with low and middle incomes and in Middle Eastern countries and East/Southeast Asia compared to those in other regions (P < 0.001). The increasing concentrations of BTEX in winter and autumn followed by the summer season and during rainy/wet weather appear to be reasonably consistent despite variations in study methods, quality, or geography. Therefore, it is recommended that more serious control measures are considered for decreasing exposure to BTEX in these climatic conditions.

PFOA and testis cancer in the Veneto Region (Italy).

The largest documented episode of human contamination by PFOA in the world (approximately 150,000 actual residents on 1 January 2020) has occurred in Italy's Veneto Region. In this large, mostly flat plain area, a cluster of testicular cancers has also been observed. Preliminary data are reported, and the most relevant and recent recommendations regarding the health surveillance of exposed individuals are emphasized.

Official health communications are failing PFAS-contaminated communities.

BACKGROUND: Environmental health agencies are critical sources of information for communities affected by chemical contamination. Impacted residents and their healthcare providers often turn to federal and state agency webpages, fact sheets, and other documents to weigh exposure risks and interventions. MAIN BODY: This commentary briefly reviews scientific evidence concerning per- and polyfluoroalkyl substances (PFAS) for health outcomes that concern members of affected communities and that have compelling or substantial yet differing degree of scientific evidence. It then features official documents in their own language to illustrate communication gaps, as well as divergence from scientific evidence and from best health communication practice. We found official health communications mostly do not distinguish between the needs of heavily contaminated communities characterized by high body burdens and the larger population with ubiquitous but substantially smaller exposures. Most health communications do not distinguish levels of evidence for health outcomes and overemphasize uncertainty, dismissing legitimate reasons for concern in affected communities. Critically, few emphasize helpful approaches to interventions. We also provide examples that can be templates for improvement. CONCLUSIONS: Immediate action should be undertaken to review and improve official health communications intended to inform the public and health providers about the risks of PFAS exposure and guide community and medical decisions.

Do hospital workers experience a higher risk of respiratory symptoms and loss of lung function?

BACKGROUND: Hospital work environment contains various biological and chemical exposures that can affect indoor air quality and have impact on respiratory health of the staff. The objective of this study was to investigate potential effects of occupational exposures on the risk of respiratory symptoms and lung function in hospital work, and to evaluate potential interaction between smoking and occupational exposures. METHODS: We conducted a cross-sectional study of 228 staff members in a hospital and 228 employees of an office building as the reference group in Shiraz, Iran. All subjects completed a standardized ATS respiratory questionnaire and performed a spirometry test. RESULTS: In Poisson regression, the adjusted prevalence ratios (aPR) among the hospital staff were elevated for cough (aPR 1.90, 95% CI 1.15, 3.16), phlegm production (aPR 3.21, 95% CI 1.63, 6.32), productive cough (aPR 2.83, 95% CI 1.48, 5.43), wheezing (aPR 3.18, 95% CI 1.04, 9.66), shortness of breath (aPR 1.40, 95% CI 0.93, 2.12), and chest tightness (aPR 1.73, 95% CI 0.73, 4.12). Particularly laboratory personnel experienced increased risks of most symptoms. In linear regression adjusting for confounding, there were no significant differences in lung function between the hospital and office workers. There was an indication of synergism between hospital exposures and current smoking on FEV1/FVC% (interaction term ß = - 5.37, 95% CI - 10.27, - 0.47). CONCLUSIONS: We present significant relations between hospital work, especially in laboratories, and increased risks of respiratory symptoms. Smoking appears to enhance these effects considerably. Our findings suggest that policymakers should implement evidence-based measures to prevent these occupational exposures.

Occurrence of respiratory symptoms and lung function deficits among fruit and vegetable market workers.

OBJECTIVE: The objective of this study was to investigate the potential effects of occupational exposures among fruit and vegetable market workers on the occurrence of respiratory symptoms and on the level of lung function parameters. METHODS: We conducted a cross-sectional study of 140 men working as fruit and vegetable market workers (response rate 100%) and a reference group of 77 male office workers as the reference group (response rate 55%) from Shiraz, Iran. The outcomes of interest included occurrence of respiratory symptoms assessed by a standard respiratory questionnaire and lung function assessed by spirometry. RESULTS: In Poisson regression analyses, the exposed group showed increased prevalence ratio (PR) of wheezing (adjusted PR 5.32, 95% CI 1.40 to 20.26), after controlling for confounding. Cough (PR 3.30, 95% CI 1.16 to 9.40) and wheezing (PR 9.40, 95% CI 2.28 to 38.64) showed increased PRs among vegetable distributors. Forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity were significantly decreased among exposed workers after controlling for confounders. The absolute value of FEV1 level was reduced significantly among fruit and vegetable carters (-0.99, 95% CI -1.68 to -0.32) and vegetable (-0.51, 95% CI -0.93 to -0.10) and fruit (-0.51, 95% CI -0.86 to -0.15) distributors in comparison with the reference group in the adjusted full model. CONCLUSIONS: This study provides evidence that fruit and vegetable market workers are at an increased risk of respiratory symptoms and reduced lung function. Workplace conditions and safety training clearly need improvement, and there is a likely role for proper use of personal protective equipment.

Occupational exposures and respiratory symptoms and lung function among hairdressers in Iran: a cross-sectional study.

OBJECTIVE: Exposures at hairdressers' work have been reported to lead to an increased risk of several health outcomes. The present study aimed to investigate the relations between occupational exposures and respiratory symptoms and lung function among hairdressers in Iran. METHODS: We conducted a cross-sectional study to compare potential respiratory effects among 140 women working as hairdressers to such effects among 140 women working as office workers (administrative personnel). Both groups worked in Shiraz, Iran. Respiratory symptoms were assessed by a standard respiratory questionnaire. The questionnaire also inquired about substances used and workspace conditions, including ventilation type. Lung function levels were measured by spirometry. RESULTS: Respiratory symptoms, including cough, wheezing, shortness of breath, and chest tightness were significantly more frequent in hairdressers compared to the reference group (p < 0.05). After controlling for potential confounders, hairdressers had a prevalence ratio (PR) of 2.18 (95% CI 1.26-3.77) for cough, 9.59 (95% CI 1.004-91.73) for wheezing, 2.06 (95% CI 1.25-3.39) for shortness of breath, and 3.31 (95% CI 1.84-5.97) for chest tightness compared to the reference group. Lung function parameters (including VC, FVC, and FEV1) were significantly reduced in hairdressers (p < 0.001). Absence of air conditioning predicted greater reduction in lung function (p < 0.05) in the exposed. Decrease in FVC with normal FEV1/FVC in the exposed group suggested existence of restrictive lung function. CONCLUSIONS: This study provides evidence of increased prevalence of respiratory symptoms and restrictive lung function impairment among hairdressers in Iran.

Perfluoroalkyl acids serum concentrations and their relationship to biomarkers of renal failure: Serum and urine albumin, creatinine, and albumin creatinine ratios across the spectrum of glomerular function among US adults.

Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged ≥ 20 years (N = 8220) in the National Health and Nutrition Examination Survey for 2005-2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (eGFR 60-89 mL/min/1.73 m2), GF-3A (45-59 mL/min/1.73 m2), and GF-3B/4 (15-44 mL/min/1.73 m2). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2-3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes.

Perfluoroalkyl substances follow inverted U-shaped distributions across various stages of glomerular function: Implications for future research.

Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007-2014 were analyzed to evaluate distributional characteristics of selected perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60-89 mL/min/1.73 m2), GF-3A (eGFR 45-59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15-44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.

Biomonitoring-based exposure assessment of benzene, toluene, ethylbenzene and xylene among workers at petroleum distribution facilities.

Elevated emissions of volatile organic compounds, including benzene, toluene, ethylbenzene, and o, p, and m-xylenes (BTEX), are an occupational health concern at oil transfer stations. This exploratory study investigated personal exposure to BTEX through environmental air and urine samples collected from 50 male workers at a major oil distribution company in Iran. Airborne BTEX exposures were evaluated over 8h periods during work-shift by using personal passive samplers. Urinary BTEX levels were determined using solid-phase microextraction with gas chromatography mass spectrometry for separation and detection. Mean exposure to ambient concentrations of benzene differed by workers' job type: tanker loading workers (5390µg/m3), tank-gauging workers (830µg/m3), drivers (81.9µg/m3), firefighters (71.2µg/m3) and office workers (19.8µg/m3). Exposure across job type was similarly stratified across all personal exposures to BTEX measured in air samples with maximum concentrations found for tanker loading workers. Average exposures concentrations of BTEX measured in urine were 11.83 ppb benzene, 1.87 ppb toluene, 0.43 ppb ethylebenzene, and 3.76 ppb xylene. Personal air exposure to benzene was found to be positively associated with benzene concentrations measured in urine; however, a relationship was not observed to the other BTEX compounds. Urinary exposure profiles are a potentially useful, noninvasive, and rapid method for assessing exposure to benzene in a developing and relatively remote production region.

BTEX exposure assessment and quantitative risk assessment among petroleum product distributors.

The aim of this study was to evaluate benzene, toluene, ethylbenzene, and xylene (BTEX) exposure among workers at four stations of a major oil distribution company. Personal BTEX exposure samples were collected over working shift (8h) for 50 workers at four stations of a major oil distribution company in Iran. Measured mean values for workers across four sites were benzene (2437, 992, 584, and 2788µg/m3 respectively), toluene (4415, 2830, 1289, and 9407µg/m3), ethylbenzene (781, 522, 187, and 533µg/m3), and xylene (1134, 678, 322, and 525µg/m3). The maximum mean concentration measured across sites for benzene was 2788µg/m3 (Station 4), toluene was 9407µg/m3 (Station 4), ethylbenzene was 781µg/m3 (Station 1) and xylene was 1134µg/m3 (Station 1). The 8h averaged personal exposure benzene concentration exceeded the recommended value of 1600µg/m3 established by the Iranian Committee for Review and Collection of Occupational Exposure Limit and American Conference of Governmental Industrial Hygienists. Mean values for excess lifetime cancer risk for exposure to benzene were then calculated across workers at each site. Estimates of excess risk ranged from 1.74 ± 4.05 (Station 4) to 8.31 ± 25.81 (Station 3). Risk was assessed by calculation of hazard quotients and hazard indexes, which indicated that xylene and particularly benzene were the strongest contributors. Tanker loading was the highest risk occupation at these facilties. Risk management approaches to reducing exposures to BTEX compounds, especially benzene, will be important to the health of workers in Iran.

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population.

BACKGROUND: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. METHODS: Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. RESULTS: CRC showed a strong inverse, dose-response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend < 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10-15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. CONCLUSIONS: In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis.

Urinary polycyclic aromatic hydrocarbon biomarkers and diabetes mellitus.

OBJECTIVE: The aim of the current study is to investigate the association of polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants, with diabetes mellitus. Animal studies link PAHs to inflammation and subsequent development of diabetes mellitus. In addition, occupational studies suggest that exposure to other aromatic hydrocarbons such as dioxins may be associated with diabetes risk in humans. DESIGN: We examined participants from the merged National Health and Nutrition Examination Survey 2001-2002, 2003-2004 and 2005-2006. Exposures of interest were eight urinary monohydroxy-PAHs. Our outcome was diabetes mellitus defined as a glycohemoglobin level (HbA1c) ≥6.5%, a self-reported physician diagnosis of diabetes or use of oral hypoglycaemic medication or insulin. Analyses were adjusted for age, sex, body mass index, race, alcohol consumption, poverty-income ratio, total cholesterol and serum cotinine. RESULTS: We observed a positive association between urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed low molecular weight (LMW) PAH biomarkers, and diabetes mellitus. Compared with participants with summed LMW PAH biomarkers in the lowest quartile, the multivariable-adjusted OR of diabetes mellitus among those in the highest quartile was 3.1 (95% CI 1.6 to 5.8). CONCLUSIONS: Urinary biomarkers of 1 and 2-hydroxynapthol, 2-hydroxyphenanthrene and summed LMW PAH biomarkers are associated with diabetes mellitus in US adults 20-65 years of age. The association of a one-time biomarker of PAH exposure has limitations commonly associated with cross-sectional studies, yet is consistent with experimental animal data and is worthy of additional consideration.

Perfluorocarbons and Gilbert syndrome (phenotype) in the C8 Health Study Population.

BACKGROUND: Gilbert syndrome (GS) is an inherited defect of bilirubin conjugation, most commonly caused by a gene mutation for the enzyme UGT1A. GS is known to affect the metabolism and excretion of drugs and xenobiotics. Perfluorocarbon compounds (PFCs) are bio-persistent environmental contaminants that affect metabolic regulation. In this study, we examined the associations of GS phenotype and serum PFCs in the C8 Health Study Population. MATERIALS AND METHODS: Using 2005-2006 data from a large PFC-exposure population survey, we compared serum PFCs concentrations between GS and non GS clinical phenotypes, in a cross sectional design, adjusting for standard risk factors, including age, BMI, smoking status, socioeconomic status and gender. RESULTS: Among 10 PFC compounds considered, only perfluorohexanoic acid (PFHxA) was seen at a significantly higher concentration in GS men and women. CONCLUSION: PFHxA exposure may be associated with GS. Our findings do not support increased exposure in GS for other PFCs.

Circulating maternal perfluoroalkyl substances during pregnancy in the C8 Health Study.

Perfluoroalkyl substances are manmade chemicals used in many consumer products and have become ubiquitous in the environment. Animal studies and a limited number of human studies have demonstrated developmental effects in offspring exposed to perfluoroalkyl substances in utero, but the implications of timing of in utero exposure have not been systematically investigated. The present study investigated variation in perfluorocarbon levels of 9952 women of childbearing age who had been exposed to perfluorooctanoic acid (PFOA) in drinking water contaminated by industrial waste. An analysis of variance with contrast was performed to compare the levels of PFOA and perfluorooctanesulfonic acid (PFOS) in pregnant and nonpregnant women overall and during each trimester of pregnancy. We found that pregnant women had lower circulating PFOA and PFOS concentrations in peripheral blood than nonpregnant women and that PFOA levels were consistently lower throughout all trimesters for pregnancy, suggesting transfer to the fetus at an early stage of gestation. These results are discussed in the context of the endocrine-disrupting properties of perfluoroalkyl substances that have been characterized in animal and human studies. Our conclusion is that further, systematic study of the potential implications of intrauterine perfluorocarbon exposure during critical periods of fetal development is urgently needed.

Polycyclic aromatic hydrocarbon biomarkers and serum markers of inflammation. A positive association that is more evident in men.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants, occurring from anthropogenic and natural sources. Several animal studies have reported a positive association of PAHs with inflammation. However, it is not clear if lower background exposure to PAHs is associated with inflammation in humans, independent of smoking, a major source of PAHs. METHODS: We examined participants from the National Health and Nutrition Examination Survey 2001-2002, 2003-2004, and 2005-2006. Our exposures of interest were eight urinary monohydroxy polycyclic aromatic hydrocarbon biomarkers. Our outcomes were serum markers of inflammation; C-reactive protein (CRP) (≤10 mg/L) and total white blood cell (WBC) count (4000-12,000 cells/µL). RESULTS: Compared to participants with summed biomarkers of low-molecular weight (LMW) PAHs in the lowest quartile, the multivariable odds ratios (95% confidence interval) of high serum CRP (≥3 mg/L) and high total WBC count (defined as at or above the 95 percentile of total WBC distribution) among participants in the highest exposure quartile were 1.77 (1.13, 2.76) and 1.34 (1.12, 1.60) respectively. Urinary 1-hydroxypyrene, the biomarker of the higher molecular weight pyrene, was positively associated with total WBC count, and to lesser extent with serum CRP. In subsequent analyses, the positive association between LMW PAHs and serum CRP and total WBC count was found to be present within the stratified subgroups, independent of smoking and other potential confounders. The positive association was more evident among adult males when compared to females. CONCLUSIONS: Urinary PAH biomarkers were found to be positively associated with serum CRP and total WBC count independent of smoking and other potential confounders. The association was more evident in men.

Factors affecting serum PFAS concentrations among US females with surgically and naturally induced menopause: data from NHANES 2003-2018.

Sex hormones influence excretion of the biopersistent per-and polyfluoroalkyl substances (PFAS) in rodents, but such influences in human studies are less clear. Data from National Health and Nutrition Examination Survey (NHANES) for 2003-2018 for US females aged ≥ 20 years who reported having hysterectomy (HYST, N=1064) and who reported being in natural menopause (MENOP, N=1505) were analyzed for associations of ever use of birth control pills, past pregnancies, live births, and other factors with serum concentrations of six per- and polyfluoroalkyl substances (PFAS). For both HYST and MENOP, PFAS concentrations computed as adjusted geometric means (AGM) were higher among those who took female replacement hormone therapy (HRT) compared to nonusers in multivariable adjusted models, for example PFOS in HRT takers (10.70 ng/mL; 95% C.I. 9.46-12.11) vs. 8.70 ng/mL (95% C.I. 8.07-9.37) in nonusers (p<0.01), and PFOA in HRT users was 2.85 ng/mL (95% C.I. 2.53-3.21) vs. 2.44 ng/mL (95% C.I. 2.32-2.36) in nonusers (p=0.01), with similar findings across race/ethnicity stratifications. HYST participants with retained ovaries sometimes had higher serum PFAS than those without ovaries in post-HYST participants not taking HRT, but results had overlapping confidence intervals in all cases and were inconsistent. PFASs were inversely associated with obesity and directly associated with higher SES as reflected in poverty income ratio (PIR) in most cases, yet HRT results for the entire population are robust to adjustments for obesity and PIR. The results suggest the hypothesis that exogenous hormone use, and specifically estrogen hormones, are associated with higher serum PFAS in postmenopausal women. We discuss potential explanations for the findings, including data from other populations that estrogens may delay the onset of kidney disease, a finding which might paradoxically increase serum PFAS among the HRT population to explain some or all of our findings in a menopausal population.

Perfluorooctanoic Acid (PFOA) Exposure and Abnormal Alanine Aminotransferase: Using Clinical Consensus Cutoffs Compared to Statistical Cutoffs for Abnormal Values.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) including perfluorooctanoic acid (PFOA) are ubiquitous environmental contaminants. Prior analysis in the large "C8 Health Project" population defined abnormal alanine aminotransferase (ALT) with statistically derived cutoffs (>45 IU/L in men, >34 IU/L in women). OBJECTIVE: To explore the degree to which PFOA was associated with modern, clinically predictive ALT biomarker cutoffs in obese and nonobese participants, excluding those with diagnosed liver disease. METHODS: We reevaluated the relationship of serum PFOA to abnormal ALT using predictive cutoff recommendations including those of the American College of Gastroenterology (ACG). Evaluations modeled lifetime cumulative exposure and measured internal PFOA exposure. RESULTS: ACG cutoff values (≥34 IU/L for males, ≥25 IU/L for females) classified 30% of males (3815/12,672) and 21% of females (3359/15,788) above ALT cutoff values. Odds ratios (OR) for above cutoff values were consistently associated with modeled cumulative and measured serum PFOA. Linear trends were highly significant. ORs by quintile showed near monotonic increases. Trends were stronger for the overweight and obese. However, all weight classes were affected. CONCLUSION: Predictive cutoffs increase the OR for abnormal ALT results. Obesity increases ORs, yet association with abnormal ALT pertains to all weight classes. The results are discussed in context of current knowledge about the health implications of PFOA hepatotoxicity.

A State-of-the-Science Review of Interactions of Per- and Polyfluoroalkyl Substances (PFAS) with Renal Transporters in Health and Disease: Implications for Population Variability in PFAS Toxicokinetics.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and have been shown to cause various adverse health impacts. In animals, sex- and species-specific differences in PFAS elimination half-lives have been linked to the activity of kidney transporters. However, PFAS molecular interactions with kidney transporters are still not fully understood. Moreover, the impact of kidney disease on PFAS elimination remains unclear. OBJECTIVES: This state-of-the-science review integrated current knowledge to assess how changes in kidney function and transporter expression from health to disease could affect PFAS toxicokinetics and identified priority research gaps that should be addressed to advance knowledge. METHODS: We searched for studies that measured PFAS uptake by kidney transporters, quantified transporter-level changes associated with kidney disease status, and developed PFAS pharmacokinetic models. We then used two databases to identify untested kidney transporters that have the potential for PFAS transport based on their endogenous substrates. Finally, we used an existing pharmacokinetic model for perfluorooctanoic acid (PFOA) in male rats to explore the influence of transporter expression levels, glomerular filtration rate (GFR), and serum albumin on serum half-lives. RESULTS: The literature search identified nine human and eight rat kidney transporters that were previously investigated for their ability to transport PFAS, as well as seven human and three rat transporters that were confirmed to transport specific PFAS. We proposed a candidate list of seven untested kidney transporters with the potential for PFAS transport. Model results indicated PFOA toxicokinetics were more influenced by changes in GFR than in transporter expression. DISCUSSION: Studies on additional transporters, particularly efflux transporters, and on more PFAS, especially current-use PFAS, are needed to better cover the role of transporters across the PFAS class. Remaining research gaps in transporter expression changes in specific kidney disease states could limit the effectiveness of risk assessment and prevent identification of vulnerable populations. https://doi.org/10.1289/EHP11885.

Association of per- and polyfluoroalkyl substance exposure with fatty liver disease risk in US adults.

Background & Aims: Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants with demonstrated hepatotoxicity. Few studies have examined the association between PFAS and fatty liver disease (FLD) risk in an adult population. Methods: In this cross-sectional study of participants from the 2017-2018 National Health and Nutrition Examination Survey, serum PFAS were measured, and FLD cases were ascertained by vibration-controlled transient elastography. Logistic regression models were used to examine the association between circulating PFAS levels and FLD risk. Analyses were stratified into non-alcoholic FLD and alcoholic FLD risk groups by alcohol intake status, as well as controlling for other risk factors, including personal demographics, lifestyle factors, and related health factors. Results: Among 1,135 eligible participants, 446 had FLD. For FLD risk, the multivariable-adjusted odds ratio per log-transformed SD increase (ORSD) in perfluorohexane sulfonate (PFHxS) was 1.13 (95% CI 1.01-1.26). The association between PFHxS and FLD appeared stronger among individuals with obesity or high-fat diets (both p interaction <0.05). When limiting the analysis to 212 heavy drinkers (≥2 drinks/day for women and ≥3 drinks/day for men), significantly higher risk of alcoholic FLD was found for higher levels of perfluorooctanoic acid (ORSD 1.79; 95% CI 1.07-2.99), PFHxS (ORSD 2.06; 95% CI 1.17-3.65), and perfluoroheptane sulfonic acid (ORSD 1.44; 95% CI 1.00-2.07), and marginally significant higher risk for total PFAS (ORSD 2.12; 95% CI 0.99-4.54). In never or light drinkers, we did not observe any significant association between PFAS and non-alcoholic FLD. Significant positive associations were found for PFAS with aspartate aminotransferase, gamma-glutamyl transaminase, total bilirubin, and albumin (ß ranged from 0.008 to 0.101, all p <0.05). Conclusions: Higher serum PFAS was moderately associated with FLD risk and worse liver function in the general population, and among those with independent risk factors, including heavy alcohol intake, obesity, or high-fat diets, PFAS increased the risk. These results suggest synergistic effects on hepatic steatosis between PFAS exposures as measured through biomonitoring data and lifestyle risk factors in a nationally representative US population. Impact and Implications: The per- and polyfluoroalkyl substances (PFAS) may convey higher risk for chronic liver disease in humans. Among 1,135 US adults in the 2017-2018 National Health and Nutrition Examination Survey, we found that higher serum PFAS was associated with higher fatty liver disease risk and worse liver function, especially among those with liver disease risk factors, including heavy alcohol intake, obesity, or high-fat diets. Continuously monitoring PFAS in the population and examining how they potentiate risk to the liver are essential.