Susan R. Woskie

NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A.

Robert E. Chapin, Jane Adams, Kim Boekelheide, L. Earl Gray Jr, Simon W. Hayward, Peter S.J. Lees, Barry S. McIntyre, Kenneth M. Portier, Teresa M. Schnorr, Sherry G. Selevan, John G. Vandenbergh, and Susan R. Woskie Pfizer, Inc., Groton, CT University of Massachusetts, Boston, MA Brown University, Providence, RI U.S. Environmental Protection Agency, Research Triangle Park, NC Vanderbilt University Medical Center, Nashville, TN Johns Hopkins University, Baltimore, MD Schering Plough Research Institute, Summit, NJ American Cancer Society, Atlanta, GA National Institute for Occupational Safety and Health, Cincinnati, OH U.S. Public Health Service (Ret), Silver Spring, MD North Carolina State University, Raleigh, NC University of Massachusetts, Lowell, MA

Skin Exposure to Isocyanates: Reasons for Concern

Objective Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. Data sources We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. Data extraction We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords “isocyanate,” “asthma,” “skin,” “sensitization,” and other synonymous terms, and our own extensive collection of isocyanate publications. Data synthesis Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. Conclusions Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.

RESPIRATORY HEALTH OF AUTOMOBILE WORKERS EXPOSED TO METAL-WORKING FLUID AEROSOLS: RESPIRATORY SYMPTOMS

A total of 1,811 automobile workers at three General Motors facilities were evaluated by questionnaire for possible respiratory effects resulting from airborne exposures to metal-working fluids (MWF): 1,042 currently worked as machinists and were exposed to one of three types of MWF aerosols (straight mineral oils, soluble oil emulsions, or water-based synthetic fluids that contained no oils); 769 assembly workers, without direct exposure, served as an internal reference group (of these, 239 had never worked as machinists). Symptoms of usual cough, usual phlegm, wheezing, chest tightness, and breathlessness, as well as physician-diagnosed asthma, and chronic bronchitis were the primary outcomes examined. Machinists as a whole had higher prevalence of cough, phlegm, wheezing, and breathlessness than that of assembly workers. Adjusting for confounding, phlegm and wheeze were associated with increasing levels of current exposure to straight oils; cough, phlegm, wheeze, chest tightness, and chronic bronchitis were associated with increasing levels of current exposure to synthetics. In models that included both past and current exposure, only current exposures to straight and synthetic fluids were associated with current symptoms.

Mortality studies of machining fluid exposure in the automobile industry. V: A case-control study of pancreatic cancer.

Results are presented from a case-control study of 97 cases of pancreatic cancer nested in a cohort of workers from three automobile manufacturing plants. Risk was examined for lifetime exposure to straight, soluble, and synthetic metalworking fluids, as used in specific machining or grinding operations, as well as for constituents of the fluids. Pancreatic cancer was associated with exposure to synthetic fluids in grinding operations, with an odds ratio of 3.0 (95% CI: 1.2-7.5) among those with more than 1.4 mg/m3-years of exposure. We were unable to examine synthetic exposure in the absence of grinding because there was virtually no exposure to synthetics in machining operations in this study population. Although a disproportionately high percent of the cases were black, no black workers had any exposure to synthetic fluids, and no other measured exposure was found to be related to risk. Thus, the previously documented excess risk of pancreatic cancer among blacks in this cohort remains unexplained.

Nanoparticles from photocopiers induce oxidative stress and upper respiratory tract inflammation in healthy volunteers

Abstract Photocopiers emit large quantities of nanoparticles (NPs); however, their toxicological properties have not been studied. Here we investigate for the first time early human responses following a days exposure to NPs from photocopiers. Nine healthy subjects spent 6 h at a busy photocopy centre on 2–3 randomly selected days. Matched nasal lavage and urine samples were collected before and at different time points post-exposure. Nasal lavage samples were analysed for 14 cytokines, inflammatory cells and total protein. Urine samples were analysed for 8-hydroxydeoxyguanosine (8-OH-dG). Exposure assessment was conducted using a suite of instruments. The mean total particle number on exposure days was >5 times higher than background, with size distributions in nanoscale range (peak 30–40 nm). Following exposure, 8-OH-dG and several pro-inflammatory cytokines were elevated 2–10 folds compared with pre-exposure levels and remained elevated for up to 36 h. We conclude that NPs from photocopiers induce upper airway inflammation and oxidative stress.

Reliable exposure assessment strategies for physical ergonomics stressors in construction and other non-routinized work

The objective of this research was to provide guidelines for the reliable assessment of ergonomics exposures in non-routinized work. Using a discrete-interval observational sampling approach, two or three observers collected a total of 5852 observations on tasks performed by three construction trades (iron workers, carpenters and labourers) for periods of several weeks. For each observation, nine exposure variables associated with awkward body postures, tool use and load handling were recorded. The frequency of exposure to each variable was calculated for each worker during each of the tasks on each of the days. ANOVA was used to assess the importance of task in explaining between-worker and within-worker variability in exposures across days. A statistical re-sampling method (bootstrap) was used to evaluate the reliability of exposure estimates for groups of workers performing the same task for different sampling periods. Most exposures were found to vary significantly across construction tasks within trade, and between-worker exposure variability was generally smaller than within-worker exposure variability within task. Bootstrapping showed that the reliability of the group estimates exposure for the most variable exposures within task tended to improve as the assessment periods approached 5 – 6 d, with marginal improvements for longer assessment periods. Reliable group estimates of exposure for the least variable exposures within task were obtained with 1 or 2 d of observation. The results of this study demonstrate that an initial estimate of the important environmental or task sources of exposure variability can be used to develop an efficient sampling strategy that provides reliable estimates of ergonomics exposures during non-routinized work.

Isocyanate Exposures in Autobody Shop Work: The SPRAY Study

Isocyanates, known to cause respiratory sensitization and asthma, are widely used in automotive refinishing where exposures to aliphatic polyisocyanates occur by both inhalation and skin contact. The work reported here, the characterization of isocyanate exposure in the autobody industry, was part of an epidemiologic study of workers in 37 autobody shops in Connecticut. This article describes workplaces, tasks, and controls, and outlines the frequency, duration, and intensity of isocyanate exposures. Personal air samples taken outside of respirators had median concentrations of 66.5 μg NCO/m3 for primer, 134.4 μg (NCO)/m3 for sealer, and 358.5 μg NCO/m3 for clearcoat. Forty-eight percent of primer, 66% of sealer, and 92% of clearcoat samples exceeded the United Kingdom Health and Safety Executive guideline for isocyanate, though none exceeded the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for monomer. Nonisocyanate-containing primers and sealers are used in more than half the shops, but nonisocyanate clearcoats are rare. Eighty-two percent of personal samples taken within a spray booth exceeded the U.K. guideline: 81% of those in downdraft spray booths, 74% in semidowndraft booths, and 92% in crossdraft booths. Only 8% of shops reported that spraying is done exclusively in spray booths. All painters wore some type of respirator. In 30% of shops, painters used supplied air respirators; the rest relied on half face organic vapor cartridge respirators with N95 overspray pads. All shops provided some type of gloves, usually latex, not recommended for isocyanate protection. Despite improvements in autobody shop materials, practices, and controls, there are still opportunities for substantial exposures to isocyanates.

A field investigation of the acute respiratory effects of metal working fluids. II. Effects of airborne sulfur exposures.

A study of cross-shift change in pulmonary function was conducted among workers exposed to metal working fluids (MWF) in an automobile parts manufacturing company. Three hundred eighty-six workers (216 machinists exposed to straight or soluble MWFs, and 170 nonmachinists) were studied for 1 day, performing spirometry at the beginning and end of their shift. Airborne concentrations of inhalable particulate, culturable bacteria, and endotoxin were measured. We observed an approximately threefold increase in the incidence of 5% or greater cross-shift decrement in forced expiratory volume during the first second among those with exposures above about 0.15 mg/m3, compared to those with exposures below about 0.08 mg/m3. There was some evidence that chronic respiratory symptoms were more prevalent among machinists than among nonmachinists, notably for chronic cough. Baseline FEV1 was about 3% lower on average among those with soluble MWF exposure compared to nonmachinists. These findings are consistent with earlier studies showing respiratory effects of MWFs.

Cohort Mortality Study of Workers Exposed to Perfluorooctanoic Acid

Perfluorooctanoic acid (PFOA) is persistent in the human body; the general population has serum levels of approximately 4 ng/mL. It causes tumors of the liver, pancreas, and testicles in rodents. The authors studied the mortality of 5,791 workers exposed to PFOA at a DuPont chemical plant in West Virginia, using a newly developed job exposure matrix based on serum data for 1,308 workers from 1979-2004. The estimated average serum PFOA level was 350 ng/mL. The authors used 2 referent groups: other DuPont workers in the region and the US population. In comparison with other DuPont workers, cause-specific mortality was elevated for mesothelioma (standardized mortality ratio (SMR) = 2.85, 95% confidence interval (CI): 1.05, 6.20), diabetes mellitus (SMR = 1.90, 95% CI: 1.35, 2.61), and chronic renal disease (SMR = 3.11, 95% CI: 1.66, 5.32). Significant positive exposure-response trends occurred for both malignant and nonmalignant renal disease (12 and 13 deaths, respectively). PFOA is concentrated in the kidneys of rodents, and there are prior findings of elevated kidney cancer in this cohort. Multiple-cause mortality analyses tended to support the results of underlying-cause analyses. No exposure-response trend was seen for diabetes or heart disease mortality. In conclusion, the authors found evidence of positive exposure-response trends for malignant and nonmalignant renal disease. These results were limited by small numbers and restriction to mortality data, which are of limited relevance for several nonfatal outcomes of a priori interest.

Summary of the Findings from the Exposure Assessments for Metalworking Fluid Mortality and Morbidity Studies

Since 1985, a number of North American researchers have evaluated the association between worker exposure to metalworking fluids (MWFs) and cancer mortality or respiratory morbidity. The studies have used different methods to measure the MWF aerosol concentration and to evaluate the exposures to the specific components of the MWF aerosol (bacteria, endotoxin, elements, metals, ethanolamines, polyaromatic hydrocarbons). This diversity of approaches makes comparison of study results difficult and has impeded the development of an occupational exposure limit (OEL) for metalworking fluids. This article summarizes the exposures measured in these North American epidemiologic studies by estimating their thoracic and inhalable MWF particulate levels. In addition, issues that must be resolved before a universal sampling and analysis method for MWF can be recommended are reviewed, including: the use of gravimetric versus extractable analysis; whether the analytical limit of detection can support a lower occupational exposure limit; if the volatile components of mineral oils should also be collected; and whether there are components of specific concern in MWFs that should be regulated separately. Finally, recommendations for future directions in MWF exposure assessment and control are suggested.