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. Employees had higher PFBS and PFBA serum concentrations than the retirees, while retirees had higher concentrations for PFOS, PFOA, and PFHxS. Compared to the 2017-2018 NHANES data, employees' PFOS and PFHxS concentrations in 2022 were two-fold higher, with PFOA levels comparable. These NHANES data did not include serum PFBS or PFBA. Cross-sectional trends of PFOS and PFOA levels from 1997 to 2022 showed PFOS declined from 151 ng/mL to 10.4 ng/mL. Similarly, PFOA decreased from 100 ng/mL to 1.5 ng/mL. A longitudinal analysis of 48 participants with measurements in both 2006 and 2022 showed concentrations decreased by 74% for PFOS and 90% for PFOA. In the mortality study, 1707 employees who worked 1 day or longer were followed for an average of 25.6 years and had 143 (8%) deaths. There were no significantly elevated risks for any specific cause of death, regardless of latency period (0 or 15 years). While no specific PFAS exposures were examined, worker mortality experience (1970-2018) was analyzed by major departments representing primary work areas. Employees and retirees at the Cordova facility continue to have elevated PFOS and PFHxS serum concentrations compared to the general population, however, their legacy PFAS concentrations have declined over time, consistent with the estimated serum elimination half-lives of these PFAS in humans assuming nominal ambient exposures. For PFBS and PFBA, the results indicated no long-term accumulation in the blood likely due to their short serum elimination half-lives. After nearly 50 years of follow-up, this Cordova workforce showed no increased risk of mortality from cancer or any other specific cause of death.

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

Per- 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). Participants completed enrollment and follow-up study visits in the Spring of 2021. Participants were categorized as cases if they reported a COVID-19 diagnosis or became sick with at least one symptom of COVID-19 when someone else in their household was diagnosed, otherwise they were categorized as a control. COVID-19 diagnosis was modeled in relation to concentration of serum PFAS measured at enrollment after adjusting for covariates. The analytic sample comprised 573 individuals, 111 cases (19.4%) and 462 controls (80.6%). In adjusted models, the odds ratio of COVID-19 was 0.94 per interquartile range (14.3 ng/mL) increase in PFOS (95% confidence interval 0.85, 1.04). Results for PFOA, PFHxS, and perfluorononanoic acid (PFNA) were similar. Other PFAS present at lower concentrations were examined as categorical variables (above the limit of quantification [LOQ], yes vs. no [referent category]), and also showed no positive associations. In our study, which used individual-level data and included people with high occupational exposure, the serum concentrations of all PFAS examined were not associated with an increased odds ratio for COVID-19. At this point, the epidemiologic data supporting no association of COVID-19 occurrence with PFAS exposure are stronger than those suggesting a positive association.

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. However, studies of antibody concentration after COVID-19 vaccination in relation to PFAS serum concentrations have not been reported. We examined COVID-19 antibody responses to vaccines and PFAS serum concentrations among employees and retirees from two 3M facilities, one of which historically manufactured PFOS, PFOA, and perfluorohexane sulfonic acid (PFHxS). Participants completed enrollment and follow-up study visits in the Spring of 2021, when vaccines were widely available. In total 415 participants with 757 observations were included in repeated measures analyses. Log-transformed concentrations of anti-spike IgG and neutralizing antibodies were modeled in relation to concentration of PFAS at enrollment after adjusting for antigenic stimulus group (9 groups determined by COVID-19 history and number and type of vaccination) and other variables. The fully adjusted IgG concentration was 3.45 percent lower (95% CI -7.03, 0.26) per 14.5 ng/mL (interquartile range) increase in PFOS; results for neutralizing antibody and PFOS were similar. For PFOA, PFHxS, and perfluorononanoic acid (PFNA), the results were comparable to those for PFOS, though of smaller magnitude. In our study data, the fully adjusted coefficients relating concentration of vaccine-induced antibodies to COVID-19 and interquartile range difference in serum concentration of PFOS, PFOA, PFHxS, and PFNA were inverse but small with confidence intervals that included zero. Our analysis showed that the coefficient for the four PFAS examined in detail was considerably affected by adjustment for antigenic stimulus group.

Reproductive and developmental toxicity of potassium perfluorohexanesulfonate in CD-1 mice.

Potassium perfluorohexanesulfonate (K+PFHxS) was evaluated for reproductive/developmental toxicity in CD-1 mice. Up to 3 mg/kg-d K+PFHxS was administered (n = 30/sex/group) before mating, for at least 42 days in F0 males, and for F0 females, through gestation and lactation. F1 pups were directly dosed with K+PFHxS for 14 days after weaning. There was an equivocal decrease in live litter size at 1 and 3 mg/kg-d, but the pup-born-to-implant ratio was unaffected. Adaptive hepatocellular hypertrophy was observed, and in 3 mg/kg-d F0 males, it was accompanied by concomitant decreased serum cholesterol and increased alkaline phosphatase. There were no other toxicologically significant findings on reproductive parameters, hematology/clinical pathology/TSH, neurobehavioral effects, or histopathology. There were no treatment-related effects on postnatal survival, development, or onset of preputial separation or vaginal opening in F1 mice. Consistent with previous studies, our data suggest that the potency of PFHxS is much lower than PFOS in rodents.

Application of a column selection system and DryLab software for high-performance liquid chromatography method development.

This paper describes a strategy for the development of chromatographic methods for drug candidates based upon the use of simple MS compatible mobile phases and optimization of the chromatographic selectivity through variations of the stationary phase and mobile phase pH. The strategy employs an automated column selection system and a series of HPLC columns, varying in hydrophobicity and silanol activity, in combination with DryLab software to develop chromatographic methods for the separation of mixtures of bupivacaine and its metabolites; acidic, basic, and neutral compounds; and atenolol, nitrendipine, and their degradation products.

Determination of bupivacaine and metabolites in rat urine using capillary electrophoresis with mass spectrometric detection.

A method using capillary electrophoresis-mass spectrometry (CE-MS) was developed for the structural elucidation of bupivacaine and metabolites in rat urine. Prior to CE-MS analysis, solid-phase extraction (SPE) was used for sample cleanup and preconcentration purposes. Exact mass and tandem mass spectrometric (MS/MS) experiments were performed to obtain structural information about the unknown metabolites. Two instruments with different mass analyzers were used for mass spectrometric detection. A quadrupole time-of-flight (Q-TOF) and a magnetic sector hybrid instrument were coupled to CE and used for the analysis of urine extracts. Hydroxybupivacaine as well as five other isomerically different metabolites were detected including methoxylated bupivacaine.