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Objectives Food processing facilities represent critical infrastructure that have stayed open during much of the COVID-19 pandemic. Understanding the burden of COVID-19 in this sector is thus important to help reduce the potential for workplace infection in future outbreaks. Methods We undertook a workplace survey in the UK food and drink processing sector and collected information on workplace size, characteristics (e.g. temperature, ventilation), and experience with COVID-19 (e.g. numbers of positive cases). For each site, we calculated COVID-19 case rates per month per 1000 workers. We performed an ecological analysis using negative binomial regression to assess the association between COVID-19 rates and workplace and local risk factors. Results Respondents from 33 companies including 66 individual sites completed the survey. COVID-19 cases were reported from the start of the pandemic up to June 2021. Respondents represented a range of industry subgroups, including grain milling/storage (n = 16), manufacture of malt (n = 14), manufacture of prepared meals (n = 12), manufacture of beverages (n = 8), distilling (n = 5), manufacture of baked goods (n = 5), and other (n = 6), with a total of 15 563 workers across all sites. Average monthly case rates per 1000 workers ranged from 0.9 in distilling to 6.1 in grain milling/storage. Incidence rate ratios were partially attenuated after adjusting for several local and workplace factors, though risks for one subgroup (grain milling/storage) remained elevated. Certain local and workplace characteristics were related to higher infection rates, such as higher deprivation (5 km only), a lower proportion of remote workers, lower proportion of workers in close proximity, and higher numbers of workers overall. Conclusions Our analysis suggests some heterogeneity in the rates of COVID-19 across sectors of the UK food and drink processing industry. Infection rates were associated with deprivation, the proportions of remote workers and workers in close proximity, and the number of workers.

Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01–1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01–1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00–1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. [Cancer Res 2009;69(17):6857–64]

Supplementary Tables 1-8 from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

Supplementary Figure Legend from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

Supplementary Figure 1 from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

Contains fulltext : 293880.pdf (Publisher’s version ) (Closed access) BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p

This review aimed to provide an overview of the literature assessing the extent of COVID-19 transmission in the food processing sector along with the risk factors associated with COVID-19 infection/mortality rates in this setting, and the preventive measures used to reduce transmission. An electronic search was conducted using scientific databases, including Web of Science, OVID, PubMed and MedRxiv. The search strategy identified 26 papers that met the inclusion criteria. Six of these studies were based in the UK and the country with the most papers was the USA, with a total of nine papers. Findings showed some evidence of a high transmission level of SARS-CoV-2 within some areas of the food production sector. Risk factors associated with the spread included ethnicity, poor ventilation, lack of social distancing and lack of sick pay. The preventative measures included/recommended were social distancing, testing, adequate ventilation, cleaning regimes and access to PPE. Additional research focusing on the food production sector could show the potential variations in transmission and risk between each sub-sector. Future research focusing on the application of various preventative measures and their efficacy by sub-sector would be beneficial, while further qualitative research could help provide in-depth information regarding knowledge gaps.

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters. Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20–64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals. Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47–4.71), HDL-C (β: 1.13, 95% CI: 0.92–1.33) and LDL-C (β: 3.14, 95% CI: 2.65–3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5–4.58), HDL-C (ψ: 1.07, 95% CI 20.87–1.27) and LDL-C (ψ: 2.71, 95% CI 2.23–3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender. Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.

Background The protective effect of community water fluoridation (CWF) against dental caries may be modified by secular changes in health behaviour. We aimed to determine the contemporary association between fluoride in public water supplies (PWS) and dental caries indicators and inequalities in England. Methods We estimated exposure to CWF and PWS fluoride concentrations from national monitoring data, using Geographic Information Systems and water supply boundaries, categorizing mean period exposure into Results The odds of caries and of severe caries in 5-year-olds fell with increasing fluoride concentration in all SES quintiles (P Conclusions Exposure to fluoride in PWS appears highly protective against dental caries and reduces oral health inequalities.

Between August-September 2021, an outbreak of SARS-CoV-2, with an attack rate of 55% (22/40 workers), occurred in a public-facing office in England. To identify workplace and worker-related risk factors, a comprehensive investigation involving surface sampling, environmental assessment, molecular and serological testing, and worker questionnaires was performed in September – October 2021. The results affirm the utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health.We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect.The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers.A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16).Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

Perfluoroalkyl substances (PFASs) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFASs is via epigenetic changes, such as DNA methylation. Previous studies have evaluated associations between PFAS exposure and DNA methylation among newborns and adults. However, no study has evaluated how PFASs influence DNA methylation among children of school age. In this exploratory study with school-age children exposed to PFASs through drinking water highly contaminated from firefighting foams, we aimed to investigate whether exposure to PFASs was associated with alteration in DNA methylation and epigenetic age acceleration. Sixty-three children aged 7–11 years from the Ronneby Biomarker Cohort (Sweden) were included. The children were either controls with only background exposure (n = 32; perfluorooctane sulfonic acid: median 2.8 and range 1–5 ng/ml) or those exposed to very high levels of PFASs (n = 31; perfluorooctane sulfonic acid: median 295 and range 190–464 ng/ml). These two groups were matched on sex, age, and body mass index. Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip kit. Epigenetic age acceleration was derived from the DNA methylation data. Twelve differentially methylated positions and seven differentially methylated regions were found when comparing the high-exposure group to the control group. There were no differences in epigenetic age acceleration between these two groups (P = 0.66). We found that PFAS exposure was associated with DNA methylation at specific genomic positions and regions in children at school age, which may indicate a possible mechanism for linking PFAS exposure to health effects.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

BACKGROUND AND AIM: Given the evidence of immunosuppression by some perfluoroalkyl substances (PFAS), there is interest in assessing if PFAS may have an impact on the risk of Coronavirus infection ...

BACKGROUND AND AIM: Air pollution is a serious public health issue and stakeholders (in particular local authorities (LA)) require more detailed information to protect those at risk. Public Health ...

BACKGROUND AND AIM: This symposium will focus attention on what characteristics might make studies have more impact on policy. It depends on the context – in my experience if the goal is to set an ...

Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production.We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders.PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (β: 8.41, 95% IC: 0.78-16.0), LDL-C (β: 8.02, 95% IC: 1-15.0) and SBP (β: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP.The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting.

Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study based on arsenic exposed 528 cases with basal cell carcinoma of skin (BCC) and 533 healthy controls, we observed a statistically significant association between decreased telomere length and increased BCC risk (OR = 5.92, 95% CI = 3.92-9.01, P1.32 µg/L) was statistically significantly associated with decreased telomere length (β = −0.026, 95% CI = − 0.05-0.003, P = 0.02). The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71-40.00, PP P = 0.0002). The combined effect of highest arsenic exposure and shortest telomeres on the risk of BCC (OR = 10.56, 95% CI = 5.14-21.70) showed a statistically significant departure from additivity (interaction constant ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.

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 PPAR alpha pathway, whereas studies on the involvement of other nuclear receptors, like PXR, are less conclusive. Other data indicate that suppression of the nuclear receptor HNF4 alpha 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.

Per- and polyfluoroalkyl substances (PFAS) are persistent substances with surfactant and repellent properties. Municipal drinking water contaminated with PFAS had been distributed for decades to one third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from December 16, 2013.The purpose was to estimate serum half-lives and their determinants in the study population for different PFAS.Up to ten blood samples were collected between 2014 and 2018 from 114 participants (age 4-84 years at entry, 53% female). 19 PFAS were analysed. Linear mixed models were used to estimate the half-lives.Eight PFAS were increased in Ronneby: perfluorooctanoic acid (PFOA), perfluoropentane sulfonate (PFPeS), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), linear perfluorooctane sulfonate (L-PFOS) and three branched perfluorooctane sulfonates (1 m-PFOS, 3/4/5m-PFOS and 2/6m-PFOS). The mean estimated half-lives (in years) were 0.94 (95 %CI 0.86-1.02) for PFPeS, 2.47 (2.27-2.7) for PFOA, 2.67 (2.51-2.85) for 2/6m-PFOS, 2.73 (2.55-2.92) for L-PFOS, 3.43 (3.19-3.71) for 3/4/5m-PFOS, 4.52 (4.14-4.99) for PFHxS, 4.55 (4.14-5.06) for PFHpS, and 5.01 (4.56-5.55) for 1 m-PFOS. The most important determinants of a shorter half-life were young age, and better kidney function measured by estimated glomerular filtration rate and ratio of paired urine and serum PFAS levels, followed by female sex during their fertile period aged 15-50. Markers of gut inflammation and reduced permeability i.e. zonulin and calprotectin were also possibly associated with shorter half-life. The results also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure.The half-life estimates are in line with past estimates for some PFAS such as PFOA, and the novel results for different PFOS isomers. These results provide observational support for elimination routes - renal, fecal and maternal.

Background Perfluoroalkyl substances (PFASs) are persistent and widespread environmental pollutants. Residents of a large area of the Veneto Region (North-Eastern Italy) were exposed to high concentrations of PFASs through drinking water from the late-1970s to 2013. PFASs have been consistently associated with raised serum lipids, but only few studies have been conducted among pregnant women, and none has stratified analyses by trimesters of gestation. Our main objective was to evaluate the association between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels and lipid profiles in high-exposed pregnant women. Methods A cross-sectional analysis was conducted in 319 pregnant women (age 14-48 years) recruited in the Regional health surveillance program. Serum PFASs were measured by HPLC-MS/MS. Non-fasting serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were measured by enzymatic assays in automated analysers, and low-density lipoprotein cholesterol (LDL-C) was calculated. The associations between ln-transformed PFASs (and categorized into quartiles) and lipids were assessed using generalized additive models. Analyses were adjusted for potential confounders and stratified according to pregnancy trimester. Results In the first trimester, plasma concentrations of both PFOA and PFOS were positively associated with TC. However in the third trimester PFOA levels were instead inversely significantly associated with TC and LDL-C levels. Overall, both PFOA and PFOS were positively associated with HDL-C, and PFOA negatively with LDL-C. Conclusions In a small highly exposed population of pregnant women, the associations between PFASs concentrations and lipid profile were modified by trimester of gestation. Patterns late in pregnancy were different to the positive associations with LDL-C generally found. Differential transfer and bioaccumulation of lipids and PFAS in the placenta across gestation might explain our findings. Key messages This study provides evidence of different patterns of PFAS associations with lipids in pregnant women across the trimesters of gestation. The different patterns of association from general population studies sheds light on the role of fetal nutrition during pregnancy affecting both lipids and PFAS in serum.

Background Residents in a large area of the Veneto Region (North-Eastern Italy) were exposed to perfluoroalkyl substances (PFASs) via drinking water. Studies on the association between PFASs and blood pressure (BP) levels are limited and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study included 16,224 individuals aged 20-39 years. Pregnant women (n = 327), participants with self-reported diagnosis or under treatment (n = 296) or with missing information on the selected covariates (n = 114) were excluded, leaving 15,487 subjects. Hypertension (HYP) was defined as any self-reported diagnosis, use of antihypertensive drugs, or raised systolic/diastolic blood pressure (SBP)≥140, DBP ≥90 mmHg). Serum PFASs were measured by HPLC-MS. Generalized additive models were used to investigate the relation between each PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) ln transformed and by decile, and SBP, DBP, HYP, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFASs concentration in a monotonic way. The predicted increase in SBP and DBP were 1.62 (95% CI = 0.69, 2.55), 1.64 mmHg (95% CI = 0.96, 2.31) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and DBP in women. One unit increase in each ln-PFAS was positively associated with an increased odds of HYP in men: PFOA OR = 1.07 (1.01-1.14), PFOS OR = 1.18 (1.05-1.32), PFHxS OR = 1.11 (1.03-1.19), PFNA OR = 1.19 (1.01-1.41). Conclusions Our findings suggest that exposure to PFAS is associated with increased blood pressure and thus may contribute as a risk factor for the development of cardiovascular diseases. Key messages Serum PFASs were associated with raised systolic blood pressure in men and diastolic blood pressure in women in a large highly exposed young adult population. Serum PFASs were associated with raised prevalence of hypertension in men.

Public health monitoring of Community Water Fluoridation (CWF) schemes requires estimates of exposure to fluoride in public water supplies (PWS). We aimed to use routine data to estimate population exposure to PWS-fluoride in England and to determine whether PWS-fluoride exposure from 2005 to 2015 could be used as a proxy for exposure for 1995–2004, when fluoride concentration data that could be linked to population health data were unavailable. We calculated annual mean water supply zone PWS-fluoride concentrations from monitoring data for 1995–2015, stratified by fluoridation scheme-flagging. We allocated annual 2005–2015 mean PWS-fluoride concentrations to small area boundaries to describe population exposure within five concentration categories (

Firefighting foam-contaminated ground water, which contains high levels of perfluoroalkyl substances (PFAS), is frequently found around airports. In 2018 it was detected that employees at a municipal airport in northern Sweden had been exposed to high levels of short-chain PFAS along with legacy PFAS (i.e., PFOA, PFHxS, and PFOS) through drinking water.In this study, we aimed to describe the PFAS profile in drinking water and biological samples (paired serum and urine) and to estimate serum half-lives of the short-chain PFAS together with legacy PFAS.Within 2 weeks after provision of clean water, blood sampling was performed in all 26 airport employees. Seventeen of them were then followed up monthly for 5 months. PFHxA, PFHpA, PFBS, PFPeS, and PFHpS together with legacy PFAS in water and biological samples were quantified using LC/MS/MS. Half-lives were estimated by assuming one compartment, first-order elimination kinetics.The proportions of PFHxA, PFHpA, and PFBS were higher in drinking water than in serum. The opposite was found for PFHxS and PFOS. The legacy PFAS accounted for about 50% of total PFAS in drinking water and 90% in serum. Urinary PFAS levels were very low compared with serum. PFBS showed the shortest half-life {average 44 d [95% confidence interval (CI): 37, 55 d]}, followed by PFHpA [62 d (95% CI: 51, 80 d)]. PFPeS and PFHpS showed average half-lives as 0.63 and 1.46 y, respectively. Branched PFOS isomers had average half-lives ranging from 1.05 to 1.26 y for different isomers. PFOA, PFHxS, and linear PFOS isomers showed average half-lives of 1.77, 2.87, and 2.93 y, respectively.A general pattern of increasing half-lives with increasing chain length was observed. Branched PFOS isomers had shorter half-lives than linear PFOS isomers. https://doi.org/10.1289/EHP6785.

Background The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a ‘probable link’ (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis. Objective Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations. Discussion For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment. Conclusion Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative.

Background Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS. Methods 1945 adults aged 20–60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI. Results Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them. Conclusions In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.

Background The use of firefighting foams at a military airport resulted in high levels of perfluorinated substances (PFAS) in the drinking water distributed to one-third of households in the Swedish municipality of Ronneby between the mid-1980s and the end of 2013. Method The Ronneby Register Cohort, a large cohort comprising all individuals (N = 60,507) who ever lived in the Ronneby municipality during the period of drinking water contamination, was linked to the Swedish Cancer Register 1985–2016. Individual exposure was classified based on comprehensive data on yearly residential address and water distribution. External analysis explored standardized cancer incidence ratios (SIR) for residents never, or ever, residing in the contaminated water district, compared with those residing in other towns in the same county as reference population. Cox models provided hazard ratios (HR) for different exposure groups within the cohort. Results 5,702 individuals with cancer were identified. SIR for overall cancer was 1.04 for men (95%CI 0.96–1.12) and 0.89 for women (95%CI 0.82–0.96) who ever lived in the contaminated drinking water area. Kidney cancer, which was reported with increased risk in C8 study, showed somewhat elevated HR in this study (HR 1.27; 95%CI 0.85–1.89). The HR was modestly elevated for bladder cancer (HR 1.32; 95%CI 1.01–1.72), and reduced for prostate cancer (HR 0.83; 95%CI 0.71–0.98). In subjects who ever lived in the contaminated water area during 2005–2013, when exposure was estimated to be highest, higher risks for kidney cancer (HR 1.84; 95%CI 1.00–3.37) but lower for prostate cancer (HR 0.76; 95%CI 0.59–0.98) were observed. Conclusion Analysis of this large cohort exposed to high levels of PFAS, dominated by PFHxS and PFOS, revealed no evidence for an overall increased risk of cancer. A moderately increased risk of kidney cancer was observed, in accordance with previous findings after PFAS exposure dominated by PFOA.

Dust elemental levels can be expressed as concentrations (bulk samples) or surface loadings (wipe samples). Wipe sampling has not been widely adopted for elements other than lead (Pb). In this study, 433 wipe samples from 130 households in south west England – a region of widespread, natural and anthropogenic arsenic contamination linked with previous mining activities-were analysed to (i) quantify loadings of arsenic (As); (ii) assess the quality of wipe data using QA/QC criteria; (iii) estimate, using published ingestion rates, human exposure to As in dust using loadings and concentrations from 97 bulk samples and (iv) comparatively assess the performance of wipe and bulk sampling using associations with As biomonitoring data (urine, toenails and hair). Good QC performance was observed for wipes: strong agreement between field duplicates, non-detectable contamination of field blank wipes and good reference material recoveries. Arsenic loadings exceeded an existing urban background benchmark in 67 (52%) households. No exceedances of tolerable daily As intake were observed for adult exposure estimates but infant estimates exceeded for 1 household. Infant estimates calculated using bulk concentrations resulted in 4 (3%) exceedances. Neither wipe nor bulk As metrics were sufficiently better predictors of As in biospecimens. Sampling strategies, analytical protocols, exposure metrics and assessment criteria require refinement to validate dust sampling methodologies.

Background: Residents of a large area of north-eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations that were quantifiable in at least 40% of samples and lipid profile, blood pressure (BP) and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14–19 years) and 2693 children (8–11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic BP were measured, and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. The weighted quantile sum regression approach was used to assess PFAS-mixture effects for each outcome. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a lesser extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Higher serum concentrations of PFAS, particularly PFOS, were associated with lower BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. These results were confirmed by the multi-pollutant analysis. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

Highlights • The literature on PFASs and circulating levels of immune cells is scarce. • Study of the association between PFASs and white blood cells at two different time points. • Cross-sectional study on the association between PFASs and lymphocyte subsets. • Positive association between PFHxS and total lymphocytes, especially for cell count. • Positive, but less consistent, association between PFOA and PFOS and total lymphocytes., Background Although perfluoroalkyl substances (PFASs) may be immunotoxic, evidence for this in humans is scarce. We studied the association between 4 PFASs (perfluorohexane sulfonate [PFHxS], perfluorooctanoic acid [PFOA], perfluorooctane sulfonate [PFOS] and perfluorononanoic acid [PFNA]) and circulating levels of several types of immune cells. Methods Serum PFASs and white blood cell types were measured in 42,782 (2005–2006) and 526 (2010) adults from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Ln(cell counts) and percentages of cell counts were regressed on serum PFAS concentrations (ln or percentiles). Adjusted results were expressed as the percentage difference (95% CI) per interquartile range (IQR) increment of each PFAS concentration. Results Generally positive monotonic associations between total lymphocytes and PFHxS, PFOA, and PFOS were found in both surveys (difference range: 1.12–7.33% for count and 0.36–1.77 for percentage, per PFAS IQR increment), and were stronger for PFHxS. These associations were reflected in lymphocyte subset counts but not percentages, with PFHxS positively and monotonically associated with T, B, and natural killer (NK) cell counts (range: 5.51–8.62%), PFOA and PFOS with some T-cell phenotypes, and PFOS with NK cells (range: 3.12–12.21%), the associations being monotonic in some cases. Neutrophils, particularly percentage (range: −1.74 to −0.36), showed decreasing trends associated with PFASs. Findings were less consistent for monocytes and eosinophils. Conclusion These results suggest an association between PFHxS and, less consistently, for PFOA and PFOS, and total lymphocytes (although the magnitudes of the differences were small). The increase in absolute lymphocyte count appeared to be evenly distributed across lymphocyte subsets since associations with their percentages were not significant.

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.

Background Perfluoroalkylated substances (PFAS) in serum are inversely associated with fetal growth. Small for gestational age (SGA) is a measure based on birth weight and gestational age at birth and represents a good indicator of fetal growth but it has been used only in a small number of studies. We examined the association between PFAS exposure and the risk of severe SGA in a PFAS contaminated area in the Veneto Region (North-East of Italy). Methods A retrospective cohort study has been developed including all singleton live births reported in the Veneto Region Birth Registry between 2003 and 2018 to mothers living in the contaminated and in a control area. We estimated the association between mothers’ area of residence and severe SGA using crude RR (and 95% CI) and stepwise logistic regression, including all the maternal characteristics. Results The study included 105,114 singleton live births. The occurence of severe SGA was 3.44% in the contaminated area and 2.67% in the control area. The multivariate analysis confirmed that living in the contaminated area significantly increased the odds of severe SGA (adjusted OR 1.27 (95% C.I. 1.16, 1.39)). Conclusions The findings suggest that living in a contaminated area by PFAS plays a role in affecting fetal growth and support the hypothesis that PFAS exposure is a risk factor for SGA. Individual data on exposure are needed to confirm the direct association.

the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs.to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs.based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels.all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of exposure which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakeholders throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals.based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.

industrially contaminated sites (ICSs) have been recognised as a major public health concern since they involve exposure to multiple environmental stressors, normally distributed unevenly within population. The COST Action on Industrially Contaminated Sites and Health Network (ICSHNet) comprises a European network of experts and institutions to clarify needs and priorities for better characterising the impact on environment and health of ICS.evaluate the availability of information and studies concerning selected ICSs in participating Countries within the ICSHNet, with particular consideration on the accessibility to environmental, health and demographic data, and research and assessment tools.to evaluate the availability of data, an Action Questionnaire (AQ) was developed based on previous questionnaires used in different European projects and on expert consultation. The AQ, with 84 items organised in eight sections, was adapted to an on-line version using the software LimeSurvey. The survey was sent to 47 participants within the ICSHNet, to report over a list of 99 ICSs previously identified.information was gathered from 81 sites out of the initially selected 99, reported by 45 participants from 27 Countries (82% of Countries in the ICSHNet). The predominant polluting activities were waste disposal (46%) and chemical industries (37%), affecting all environmental media, but more extensively surface and groundwater (70%) and soil (68%). Main categories of contaminants affecting different media were heavy metals and chlorinated hydrocarbons, but also BTEX (benzene, toluene, ethylbenzene, and xylene) and ambient air pollutants (e.g., particulate matter, SOx). Human health risk assessment was the most prevalent methodological approach for characterising impacts on health (32%), followed by epidemiological studies (26%), and health impact assessment (12%). The low reporting, both referring to data availability or methodologies, could be due to absence of data, or to the fact that the reporting person (many of them from the public health sector) did not know how to reach the environmental information.survey findings suggest that improving the collection and access to specific environmental, health and demographic data related to ICSs is crucial to meet the methodological requirement to better analyse the health impact of ICSs.