Critical review and synthesis of the epidemiologic evidence on formaldehyde exposure and risk of leukemia and other lymphohematopoietic malignancies.

PURPOSE: Recent epidemiologic studies indicate elevated risks for some lymphohematopoietic malignancies (LHM) related to formaldehyde exposure. We performed a systematic review of literature to assess the strength and consistency of associations. METHODS: We summarized published literature in the PubMed database of the National Library of Medicine during 1966-2012. Literature was categorized according to study design and population: industrial cohort studies, professional cohort studies, and population-based case-control studies. RESULTS: Findings from occupational cohort and population-based case-control studies were very inconsistent for LHM, including myeloid leukemia. Apart from some isolated exceptions, relative risks were close to the null, and there was little evidence for dose-response relations for any of the LHM. CONCLUSIONS: At present, there is no consistent or strong epidemiologic evidence that formaldehyde is causally related to any of the LHM. The absence of established toxicological mechanisms further weakens any arguments for causation. To be informative, future epidemiologic research should improve on formaldehyde exposure assessment and apply modern diagnostic schemes for specific LHM.

Exposure registries: overview and utility for nanomaterial workers.

OBJECTIVE: This article provides the background for consideration of exposure registries to address potential disease risks in nanomaterial workers. METHODS: The history of exposure registries is reviewed with a focus on their purpose and criteria for establishment. RESULTS: A rationale is presented for developing registries of nanomaterial workers, and unresolved obstacles and challenges are identified. These include issues on inclusion criteria, funding, potential for legal risks, access to data, confidentiality of business information, privacy, and workers' expectations. CONCLUSION: If society is to gain the benefits from nanotechnology, it must take precautions and demonstrate care for those, such as workers, who may be most at risk of adverse effects. Establishing exposure registries is a part of such a precautionary and caring approach.

Epidemiological studies of formaldehyde exposure and risk of leukemia and nasopharyngeal cancer: a meta-analysis.

The authors conducted meta-analyses of the epidemiological literature on formaldehyde exposure and risk of leukemia and risk of nasopharyngeal cancer. The authors abstracted study results and confounder information from cohort and case-control studies, and used quantile plots and regression models to evaluate heterogeneity and possible publication bias. No evidence of serious heterogeneity or publication bias was seen. For leukemias, the summary relative risk (RR) was 1.05 (95% confidence interval [CI]: 0.93, 1.20) for cohort studies, and the summary odds ratio (OR) was 0.99 (95% CI: 0.71, 1.37) for case-control studies. Based on cohort and case-control studies, no significant differences were seen by leukemia subtype, job type, publication period, or region. Summary estimates for nasopharyngeal cancers were not elevated after excluding a single plant with an unexplained cluster of nasopharyngeal cancers (cohort RR = 0.72, 95% CI: 0.40, 1.28). The summary estimate was increased for case-control studies overall, but the summary OR for smoking-adjusted studies was 1.10 (95% CI: 0.80, 1.50). Previous meta-analyses showed elevated summary estimates for leukemia; however, these analyses included results from proportionate mortality studies and did not explore other factors that could influence or confound results. By limiting analyses to stronger case-control and cohort study designs, considering the effects of smoking and ignoring anomalous results from a single plant, our meta-analyses provide little support for a causal relationship between formaldehyde exposure and leukemia or nasopharyngeal cancer.

Meta-analyses of occupational exposure as a painter and lung and bladder cancer morbidity and mortality 1950-2008.

The International Agency for Research on Cancer (IARC) classified occupational painting as a human carcinogen based on lung and bladder cancers; however, no specific exposures were implicated. The authors conducted comprehensive meta-analyses of the epidemiological literature on occupational painting and these cancers. The authors abstracted study results and confounder information, and used quantile plots and regression models to evaluate heterogeneity and publication bias. Summary risk estimates were derived and sensitivity analyses performed to evaluate smoking, socioeconomic status (SES), and exposure variables. Where applicable, a Bayesian approach was used to externally adjust for smoking, a major risk factor for both cancers. For lung cancer cohort mortality studies, publication bias and heterogeneity were seen, and earlier studies reported higher risk estimates than later studies. Overall lung cancer summary risk estimates were 1.29 for case-control and 1.22 and 1.36 for cohort morbidity and mortality studies, respectively, and risk estimates for bladder cancer were 1.28 for case-control and 1.14 and 1.27 for cohort morbidity and mortality studies, respectively (all statistically significant). Risks did not differ between painters and mixed occupations. Nonsignificant summary estimates resulted for lung and bladder cancers when controlling for SES, or externally adjusting for smoking in lung cancer studies. Summary risks varied by control source for case-control studies. Residual confounding by smoking and SES, lack of exposure group effect, and publication bias limit the ability of the meta-analyses to explain associations observed between occupational painting and lung and bladder cancers. Given the long latencies for lung and bladder cancers, these weak associations, if real, may not be elucidated through studies of occupational painting today.

A historical review of additives and modifiers used in paving asphalt refining processes in the United States.

The U.S. asphalt paving industry has evolved over time to meet various performance specifications for liquid petroleum asphalt binder (known as bitumen outside the United States). Additives to liquid petroleum asphalt produced in the refinery may affect exposures to workers in the hot mix paving industry. This investigation documented the changes in the composition and distribution of the liquid petroleum asphalt products produced from petroleum refining in the United States since World War II. This assessment was accomplished by reviewing documents and interviewing individual experts in the industry to identify current and historical practices. Individuals from 18 facilities were surveyed; the number of facilities reporting use of any material within a particular class ranged from none to more than half the respondents. Materials such as products of the process stream, polymers, elastomers, and anti-strip compounds have been added to liquid petroleum asphalt in the United States over the past 50 years, but modification has not been generally consistent by geography or time. Modifications made to liquid petroleum asphalt were made generally to improve performance and were dictated by state specifications.

A review of changes in composition of hot mix asphalt in the United States.

This review researched the materials, methods, and practices in the hot mix asphalt industry that might impact future exposure assessments and epidemiologic research on road paving workers. Since World War II, the U.S. interstate highway system, increased traffic volume, transportation speeds, and vehicle axle loads have necessitated an increase in demand for hot mix asphalt for road construction and maintenance, while requiring a consistent road paving product that meets state-specific physical performance specifications. We reviewed typical practices in hot mix asphalt paving in the United States to understand the extent to which materials are and have been added to hot mix asphalt to meet specifications and how changes in practices and technology could affect evaluation of worker exposures for future research. Historical documents were reviewed, and industry experts from 16 states were interviewed to obtain relevant information on industry practices. Participants from all states reported additive use, with most being less than 2% by weight. Crumb rubber and recycled asphalt pavement were added in concentrations approximately 10% per unit weight of the mix. The most frequently added materials included polymers and anti-stripping agents. Crumb rubber, sulfur, asbestos, roofing shingles, slag, or fly ash have been used in limited amounts for short periods of time or in limited geographic areas. No state reported using coal tar as an additive to hot mix asphalt or as a binder alternative in hot mix pavements for high-volume road construction. Coal tar may be present in recycled asphalt pavement from historical use, which would need to be considered in future exposure assessments of pavers. Changes in hot mix asphalt production and laydown emission control equipment have been universally implemented over time as the technology has become available to reduce potential worker exposures. This work is a companion review to a study undertaken in the petroleum refining sector that investigated current and historical use of additives in producing petroleum-derived asphalt cements.

Options for occupational health surveillance of workers potentially exposed to engineered nanoparticles: state of the science.

OBJECTIVE: Health authorities, employers, and worker representatives are increasingly faced with making decisions about occupational health surveillance of workers potentially exposed to engineered nanoparticles. This article was developed to identify options that can be considered. METHODS: The published scientific literature on health effects from engineered and incidental nanoparticles and the principles of occupational health surveillance were reviewed to describe possible options and the evidence base for them. RESULTS: Various options for occupational health surveillance were identified. The options ranged from no action targeted to nanotechnology workers to an approach that includes documentation of the presence of engineered nanoparticles, identification of potentially exposed workers, and general and targeted medical testing. CONCLUSIONS: Although the first priority should be to implement appropriate primary preventive measures, additional efforts to monitor employee health may be warranted. Continued research is needed, and the collection of such information for exposure registries may be useful for future epidemiologic studies.

Clinical epidemiological study of employees exposed to surfactant blend containing perfluorononanoic acid.

INTRODUCTION: An epidemiological study was conducted of a perfluorononanoic acid (PFNA) surfactant blend, to investigate whether clinical differences were apparent between employees who were potentially exposed to the surfactant and those who were not exposed. The surfactant blend, which is related to other previously studied perfluorinated materials, is used in the production of some high-performance polymers. METHODS: All 630 individuals employed at a polymer production facility using PFNA (CAS No 72968-38-8) at any time between 1 January 1989 and 1 July 2003 were included in the cohort. Plausibly related laboratory test results were abstracted from annual medical examination records, including liver enzyme function and blood lipids. Detailed work histories, available for all employees, provided the basis for determining exposure category. Thirty two clinical parameters were evaluated by exposure level at five points in time, determined to reflect changes in possible exposure intensity, as well as greatest number of records available. Annual cross-sectional analyses and longitudinal analyses that accounted for multiple measurements per person were conducted separately for men and women, by exposure groups. RESULTS: Differences by exposure group for all laboratory measures, adjusted for age and body mass index, were small and not clinically significant. Although some statistically significant pair-wise differences were observed, these observations were not consistent between men and women, or over the five analysis windows. For the seven outcome variables (liver enzymes and blood lipids) examined in separate longitudinal models, no significant increase or decrease was observed by unit increase in cumulative exposure intensity score. CONCLUSION: This is the first epidemiological study investigating the possible health effects in humans associated with exposure to PFNA blend. Based on laboratory measures assessed over more than a decade, no adverse clinical effects were detected from occupational exposure to PFNA blend.

Lung cancer mortality in the German chromate industry, 1958 to 1998.

OBJECTIVES: We conducted a mortality study of two German chromate production facilities and evaluated possible dose-response relationships between hexavalent chromium exposure and lung cancer. METHODS: Mortality was followed-up through 1998 and limited to those employed since each plant converted to a no-lime production process. More than 12,000 urinalysis results of chromium levels were available, as was smoking information. RESULTS: All-cause mortality indicated a healthy worker effect (standardized mortality ratio [SMR] = 0.80, 95% confidence interval [CI] = 0.67-0.96); however, lung cancers appeared to be increased (SMR = 1.48, 95% CI = 0.93-2.25). No clear dose-response was found in stratified analyses by duration of employment and time since hire. On the basis of urinary chromium data, lung cancer risk was elevated only in the highest exposure group (SMR = 2.09, 95% CI = 1.08-3.65). CONCLUSIONS: These data suggest a possible threshold effect of occupational hexavalent chromium exposure on lung cancer.

Cause-specific mortality among Kelly Air Force Base civilian employees, 1981-2001.

In response to concerns about occupational and environmental exposures, and a perceived cluster of amyotrophic lateral sclerosis (ALS) in the community, the mortality experience among 31,811 civilian employees who worked for at least 1 year between 1981 and 2000 at Kelly Air Force Base, Texas was ascertained. A total of 3264 deaths occurred through October 31, 2001. Overall, significant deficits in mortality were observed for all causes of death and all cancers combined. An excess of breast cancer [standardized mortality ratio (SMR) = 216; 95% confidence interval (CI) = 128-341] among blue-collar women was identified, and remained elevated after adjusting for race and ethnicity [rate ratio (RR) = 2.83; 95% CI = 1.50-5.34]. Mortality from motor neuron disease, which includes ALS deaths, was not increased overall (SMR = 0.98; 95% CI = 0.52-1.68), and was lower among blue-collar employees and higher among white-collar employees than expected, based on small numbers. Overall, mortality patterns indicated a healthy worker population and no large increased mortality associated with employment at Kelly Air Force Base.

Adrenocortical neoplasms in childhood and adolescence: Analysis of prognostic factors including DNA content.

Thirty-two adrenocortical neoplasms in children and adolescents were evaluated for prognostic factors including clinical and morphological parameters and DNA ploidy. The patients were segregated into two groups according to clinical outcome: group A, represented by patients with clinically benign neoplasms (n = 15), and group B, patients with clinically malignant tumors as evidenced by local recurrence, metastases, or fatal outcome (n = 17). Clinical and morphological parameters in these two groups were evaluated using appropriate statistical methods. Parameters with a significant predictive value in terms of prognosis were age [p = .04], tumor size (p = .0003), median tumor weight (p = .0001), mitotic count (p = 0.04), and 25% tumor necrosis or more (p = .03). Twenty-three cases were studied for DNA ploidy: 10 cases by image analysis and 13 by both image analysis and flow cytometry. By ploidy analysis, 17 of 23 cases-12 of 14 in group A and 5 of 9 in group B-were found to be aneuploid. Multiple aneuploid peaks were found in 5 of 23 cases-4 of 14 cases in group A and 1 of 9 cases in group B. In tumors studied by both image analysis and flow cytometry, there was no discrepancy between results of ploidy analysis. There was no statistically significant association demonstrated between clinical outcome and DNA ploidy pattern. DNA ploidy heterogeneity, characterized by multiple aneuploid populations of cells, was also detected in both benign and malignant neoplasms. Based on our results, aneuploidy is relatively frequent in pediatrie adrenocortical tumors and does not appear to have predictive value for biological behavior.