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.

Cohort mortality study of roofing granule mine and mill workers. Part II. Epidemiologic analysis, 1945-2004.

The mortality of 2650 employees (93.4% males) in the mine and mill production of roofing granules at four plants was examined between 1945 and 2004. Hypotheses focused on diseases associated with exposure to silica: nonmalignant respiratory disease, lung cancer, and nonmalignant renal disease. Study eligibility required ≥ 1 year of employment by 2000. Work history and vital status were followed through 2004 with < 1% lost to follow-up. Industrial hygiene sampling data (1871 sampling measurements over a 32-year period) and professional judgment were used to construct 15 respirable crystalline silica exposure categories. A category was assigned to all plant-, department-, and time-dependent standard job titles. Cumulative respirable crystalline silica exposure (mg/m(3)-years) was calculated as the sum of the product of time spent and the average exposure for each plant-, department-, job-, and calendar-year combination. The cohort geometric mean was 0.17 mg/m(3)-years (geometric standard deviation 4.01) and differed by plant. Expected deaths were calculated using U.S. (entire cohort) and regional (each plant) mortality rates. Poisson regression was used for internal comparisons. For the entire cohort, 772 deaths (97.4% males) were identified (standardized mortality ratio 0.95, 95% CI 0.88-1.02). There were 50 deaths from nonmalignant respiratory diseases (1.14, 95% CI 0.85-1.51). Lagging exposure 15 years among the male cohort, the relative risks for nonmalignant respiratory disease were 1.00 (reference), 0.80, 1.94, and 2.03 (p value trend = 0.03) when cumulative exposure was categorized < 0.1, 0.1- < 0.5, 0.5- < 1.0, and ≥ 1.0 mg/m(3)-years, respectively. There was a total of 77 lung cancer deaths (1.11, 95% CI 0.88-1.39). Lagging exposure 15 years, the relative risks for males were 1.00 (reference), 1.83, 1.83, and 1.05 (p value trend = 0.9). There were 16 deaths from nonmalignant renal disease (1.76, 95% CI 1.01-2.86). This exposure-response trend was suggestive but imprecise. The study results are consistent with other cohorts with similar levels of exposure to respirable crystalline silica.

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. Vital status and cause of death were ascertained from 1945 through 2015. RCS exposure was estimated across plant-, department-, job-, and time-dependent categories using historic industrial hygiene sampling data and professional judgment. Associations between cumulative RCS (mg/m3-years) and cause-specific mortality were examined using Cox proportional hazard regression models. RESULTS: In the exposure-response analysis defined on quartiles of cumulative RCS exposure, no increasing trend (ptrend = 0.37) in lung cancer mortality (n = 116 deaths) was observed (Hazard ratio (HR) = 1.00 (referent), 1.20, 1.85, 0.92). Mortality risk for non-malignant respiratory disease was increased across quartiles (HR = 1.00, 1.35, 1.89, 1.70; ptrend = 0.15), based on 83 deaths. Non-malignant renal disease mortality was increased across quartiles (HR = 1.00, 6.64, 3.79, 3.29; ptrend = 0.11), based on 26 deaths. CONCLUSIONS: After nearly seven decades of follow-up, the exposure-response analyses showed no evidence of a positive trend for lung cancer, and limited evidence of a trend for non-malignant respiratory disease, and non-malignant renal disease mortality as a result of cumulative RCS exposure in this occupational cohort.

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.

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 (11-17.2 mg/kg). Monkeys were given routine checkups and observed carefully for health problems on a daily basis. Scheduled blood samples were drawn from all monkeys prior to, during, and after K+PFOS administration for up to 1 year and they were analyzed for PFOS concentrations and clinical chemistry markers for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. No mortality occurred during the study. All the monkeys were healthy, gained weight, and were released back to the colony at the end of the study. The highest serum PFOS achieved was approximately 165 µg/ml. When compared with time-matched controls, administration of K+PFOS to monkeys did not result in any toxicologically meaningful or clinically relevant changes in serum clinical measurements for coagulation, lipids, hepatic, renal, electrolytes, and thyroid-related hormones. A slight reduction in serum cholesterol (primarily the high-density lipoprotein fraction), although not toxicologically significant, was observed. The corresponding lower-bound fifth percentile benchmark concentrations (BMCL1sd) were 74 and 76 µg/ml for male and female monkeys, respectively. Compared to the 2013-2014 geometric mean serum PFOS level of 4.99 ng/ml (0.00499 µg/ml) in US general population reported by CDC NHANES, this represents 4 orders of magnitude for margin of 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. Based on this evaluation, the 3M CVRRP and active collaboration between participants and providers in the workplace successfully reduced modifiable CVD risk factors.

Long-term clinical outcomes following treatment of actinic keratosis with imiquimod 5% cream.

BACKGROUND: The results from four phase III, randomized, vehicle-controlled studies showed that imiquimod 5% cream (imiquimod) was safe and effective in the treatment of actinic keratosis (AK). Patients applied imiquimod or vehicle cream to AK lesions on the face or balding scalp, dosing three times per week or two times per week for 16 weeks. OBJECTIVE: To obtain long-term safety follow-up data and estimate AK recurrence in patients who completely cleared their AK lesions in the treatment area at the 8-week post-treatment visit in the phase III studies. METHODS: One hundred forty-six patients from 30 study centers in the United States were evaluated for clinical evidence of AK, and safety data were collected. RESULTS: After a median follow-up period of 16 months, 24.7% (19 of 77) of the patients administered imiquimod three times per week and 42.6% (23 of 54) of the patients administered imiquimod two times per week had a recurrence of AK (the appearance of at least one AK lesion) in the original treatment area. The median number of AK lesions present was one lesion for both patients receiving imiquimod three times and those receiving imiquimod two times per week compared with a median of six lesions at baseline in the combined three times per week and two times per week phase III studies. There were no long-term safety issues, and the skin quality seen in the imiquimod-treated patients at the end of the phase III studies was maintained. CONCLUSION: One and a half years following treatment, imiquimod continued to provide a long-term clinical benefit in a majority of patients who experienced complete clearance of their AK lesions.