Evaluation of the validity of a perfluorooctane sulfonic acid exposure reconstruction using a measured serum concentration among workers with a wide range of exposure.

Background: Studies among workers with a wide range of exposure to perfluoroalkyl substances inform risk assessments. Perfluorooctane sulfonate (PFOS), a ubiquitous environmental contaminant, was recently examined in relation to mortality and cancer incidence in an occupationally exposed population by Alexander et al. in 2024.

Mortality and cancer incidence in perfluorooctanesulfonyl fluoride production workers.

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with several health outcomes, though few occupationally-exposed populations have been studied. We evaluated mortality and cancer incidence in a cohort of perfluorooctanesulfonyl fluoride-based specialty chemical manufacturing workers.

Methods: The cohort included any employee who ever worked at the facility from 1961 to 2010 (N = 4045), with a primary interest in those who had 365 cumulative days of employment (N = 2659).

Occurrence of COVID-19 and serum - and polyfluoroalkyl substances: A case-control study among workers with a wide range of exposures.

- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Some studies suggest that certain PFAS may have immunotoxic effects in humans, which could put individuals with high levels of exposure at increased risk for infectious diseases such as COVID-19. We conducted a case-control study to examine the association between COVID-19 diagnosis and PFAS serum concentrations among employees and retirees from two 3 M facilities, one of which historically generated perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS).

An investigation of 3M Cordova, IL production worker's per- and polyfluoroalkyl substances biomonitoring results and mortality experience.

Per- and polyfluoroalkyl substances (PFAS) are a wide-ranging group of chemicals that have been used in a variety of polymer and surfactant applications. While 3M Cordova, Illinois was not one of 3M's primary manufacturing facilities for the legacy long-chain PFAS (PFOS, PFOA, PFHxS), it has been a major manufacturing site for short-chain PFAS (compounds that are or may degrade to PFBS or PFBA). The purpose of this research focused on: 1) an analysis of biomonitoring data of employees and retirees, and 2) an analysis of the cohort mortality of workers from 1970 to 2018.

Mortality among mine and mill workers exposed to respirable crystalline silica.

Background: Millions of workers are potentially exposed to respirable crystalline silica (RCS) which has been associated with several diseases. We updated the mortality experience of a cohort of 2,650 mine and mill workers at four manufacturing facilities to assess cause-specific mortality risks associated with estimated cumulative RCS exposure.

Methods: Study eligibility was defined as any employee who had ≥1 year of service by 2000, with work history experience available from 1945 through 2004.

Antibody response to COVID-19 vaccines among workers with a wide range of exposure to per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Several studies have shown associations between certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and reduced antibody concentration after vaccination against diseases such as Tetanus. Recent studies have reported associations between COVID-19 occurrence and exposure to certain types of PFAS.

Using quantitative modeling tools to assess pharmacokinetic bias in epidemiological studies showing associations between biomarkers and health outcomes at low exposures.

Biomarkers of exposure can be measured at lower and lower levels due to advances in analytical chemistry. Using these sensitive methods, some epidemiology studies report associations between biomarkers and health outcomes at biomarker levels much below those associated with effects in animal studies. While some of these low exposure associations may arise from increased sensitivity of humans compared with animals or from species-specific responses, toxicology studies with drugs, commodity chemicals and consumer products have not generally indicated significantly greater sensitivity of humans compared with test animals for most health outcomes.

A Pathology Review of the Lower Gastrointestinal Tract in Relation to Ulcerative Colitis in Rats and Cynomolgus Macaques Treated With Ammonium Perfluorooctanoate.

Among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (PFOA), the gastrointestinal tract has not been identified as a target organ for PFOA-related toxicity in laboratory animals where the corresponding serum PFOA concentrations typically approach several orders of magnitude higher than the general human population. These lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend was observed for ulcerative colitis, an idiopathic chronic inflammatory condition of the gut, in a Mid-Ohio River community whose drinking water contained higher levels of PFOA. This study was conducted to perform a histological reevaluation of large intestine sections in laboratory animals from 2 long-term toxicological studies: one was with Sprague Dawley rats that received ammonium PFOA in their diet for 2 years and the other one was with cynomolgus macaques that received daily capsules of ammonium PFOA for 6 months.

Dose Effects of Ammonium Perfluorooctanoate on Lipoprotein Metabolism in APOE*3-Leiden.CETP Mice.

Epidemiological studies have reported positive associations between serum perfluorooctanoic acid (PFOA) and total and non-high-density lipoprotein cholesterol (non-HDL-C) although the magnitude of effect of PFOA on cholesterol lacks consistency. The objectives of this study were to evaluate the effect of PFOA on plasma cholesterol and triglyceride metabolism at various plasma PFOA concentrations relevant to humans, and to elucidate the mechanisms using APOE*3-Leiden.CETP mice, a model with a human-like lipoprotein metabolism.

Stochastic Pharmacokinetic-Pharmacodynamic Modeling for Assessing the Systemic Health Risk of Perfluorooctanoate (PFOA).

A phase 1 dose-escalation trial assessed the chemotherapeutic potential of ammonium perfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer patients who failed standard therapy received weekly APFO doses (50-1200 mg) for 6 weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured predose and weekly thereafter.

Per- and polyfluoroalkyl substances (PFAS) in American Red Cross adult blood donors, 2000-2015.

In 2015, thirteen per- and polyfluoroalkyl substances (PFAS), including perfluorohexanesulfonate (PFHxS), perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA) were analyzed in human plasma that were collected from a total of 616 American Red Cross male and female blood donors (ages 20-69) at 6 regional blood collection centers. Plasma samples were analyzed using a validated solvent precipitation-isotope dilution direction-liquid chromatography tandem mass spectrometry method. The data were analyzed in conjunction with prior cross-sectional investigations [2000-2001 (n =645), 2006 (n =600), and 2010 (n =600)] to determine PFAS trends.

Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).

Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS.

Evaluation of Serum Lipid, Thyroid, and Hepatic Clinical Chemistries in Association With Serum Perfluorooctanesulfonate (PFOS) in Cynomolgus Monkeys After Oral Dosing With Potassium PFOS.

An oral dose study with perfluorooctanesulfonate (PFOS) was undertaken to identify potential associations between serum PFOS and changes in serum clinical chemistry parameters in purpose-bred young adult cynomolgus monkeys (Macaca fascicularis). In this study, control group (n = 6/sex) was sham-dosed with vehicle (0.5% Tween 20 and 5% ethanol in water), low-dose group (n = 6/sex) received 1 single K+PFOS dose (9 mg/kg), and high-dose group (n = 4-6/sex) received 3 separate K+ PFOS doses (11-17.

Temporal trends of perfluorooctanesulfonate isomer and enantiomer patterns in archived Swedish and American serum samples.

Human perfluorooctanesulfonate (PFOS) body burdens are attributable to both direct PFOS and indirect PFOS precursor (PreFOS) exposure. The relative importance of these two pathways has been estimated, but the relative temporal trajectory of exposure to PFOS and PreFOS has not been examined. Here, two hypothesized biomarkers of PreFOS exposure, PFOS isomer profiles (quantified as percent branched PFOS, %br-PFOS) and chiral 1m-PFOS enantiomer fractions (1m-PFOS EF) were analyzed in archived human serum samples of individual American adults (1974-2010) and pooled samples of Swedish primiparous women (1996-2010).

Mortality and cancer incidence in ammonium perfluorooctanoate production workers.

Objective: To evaluate mortality and cancer incidence in a cohort of ammonium perfluorooctanoate (APFO) exposed workers.

Methods: We linked a combined cohort (n=9027) of employees from APFO and non-APFO production facilities in Minnesota to the National Death Index and to cancer registries of Minnesota and Wisconsin. Industrial hygiene data and expert evaluation were used to create a task-based job exposure matrix to estimate APFO exposure.

Evaluation of a cardiovascular Risk Reduction Program at a workplace medical clinic.

The Cardiovascular Risk Reduction Program (CVRRP) was implemented in the 3M Medical Clinic in December 2009. The goal of the CVRRP was to evaluate 3M employees at risk for developing cardiovascular disease (CVD) and address any related modifiable risk factors with appropriate intervention strategies through clinic visits with a 3M nurse practitioner or physician and, if needed, a registered dietitian and/or exercise professional. Data for the first 100 participants were analyzed to initially assess the effectiveness of the program.

Longitudinal assessment of lipid and hepatic clinical parameters in workers involved with the demolition of perfluoroalkyl manufacturing facilities.

Objective: To examine in a longitudinal occupational assessment whether changes in serum concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are associated with changes in non-high-density lipoprotein (HDL) cholesterol.

Methods: Baseline and end-of-project PFOA, PFOS, lipid, and hepatic clinical chemistries were measured in 204 workers involved with the demolition of former perfluoroalkyl manufacturing facilities. Analyses were restricted to the 179 workers who did not take lipid-lowering medications.

Temporal trends of perfluoroalkyl concentrations in American Red Cross adult blood donors, 2000-2010.

Eleven perfluorinated alkyl acids (PFAAs) were analyzed in plasma from a total of 600 American Red Cross adult blood donors from six locations in 2010. The samples were extracted by protein precipitation and quantified by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). The anions of the three perfluorosulfonic acids measured were perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS).

Chronic dietary toxicity and carcinogenicity study with ammonium perfluorooctanoate in Sprague-Dawley rats.

In order to assess the potential chronic toxicity and tumorigenicity of ammonium perfluorooctanoate (APFO), a 2-year dietary study was conducted with male and female rats fed 30 ppm or 300 ppm (approximately 1.5 and 15 mg/kg). In males fed 300 ppm, mean body weights were lower across most of the test period and survival in these rats was greater than that seen either in the 30 ppm or the control group.

Cohort mortality study of roofing granule mine and mill workers. Part I: Estimation of historical crystalline silica exposures.

A study was conducted to construct a job exposure matrix for the roofing granule mine and mill workers at four U.S. plants.