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The risk of lung cancer as a result of exposure to diesel exhaust from railroad locomotives was assessed in a cohort of 55,407 white male railroad workers 40 to 64 yr of age in 1959 who had started railroad service 10 to 20 years earlier. The cohort was traced until the end of 1980, and death certificates were obtained for 88% of 19,396 deaths; 1,694 lung cancer cases were identified. Yearly railroad job from 1959 to death or retirement was available from the Railroad Retirement Board, and served as an index of diesel exhaust exposure. Directly standardized rates and a proportional hazards model were used to calculate the relative risk of lung cancer based on work in a job with diesel exhaust exposure beginning in 1959. A relative risk of 1.45 (95% CI = 1.11, 1.89) for lung cancer was obtained in the group of workers 40 to 44 yr of age in 1959, the group with the longest possible duration of diesel exposure. The cohort was selected to minimize the effect of past railroad asbestos exposure, and analysis with workers with possible asbestos exposure excluded resulted in a similarly elevated risk. Workers with 20 yr or more elapsed since 1959, the effective start of diesel exposure for the cohort, had the highest relative risk. These results taken in conjunction with other reported results support the hypothesis that occupational exposure to diesel exhaust results in a small but significantly elevated risk for lung cancer.

ObjectiveIsocyanates (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 sourcesWe 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 extractionWe 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 synthesisIsocyanate 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.ConclusionsIntegrated 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.

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.

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 day's 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.