Retrospective occupational exposure assessment for case-control and case-series epidemiology studies based in Shanghai China.

To provide exposure information for epidemiology studies conducted in Shanghai from 2001 to 2008, we completed retrospective exposure assessments (EA) of benzene and other hazards. Interviewers administered questionnaires to subjects from Shanghai area hospitals. An initial exposure screening by EA staff members, blinded as to case-control status, stratified jobs into exposed, unexposed, or uncertain categories prior to review by a separate expert panel (EP). Resources for the EA included job/industry-specific questionnaire responses by subjects, short-term benzene area concentration measurements from a Shanghai regulatory agency database, Chinese literature for qualitative and short-term quantitative measurements, on-site investigations, summaries of technology changes, and selected task simulations with concurrent benzene concentration measurements. An EP in Shanghai completed semi-quantitative benzene exposure assignments, with categories of 0 to 4 corresponding to intensity ranges of none, <1, 1 to 10, >10 to 100, and >100 mg/m(3). For other hazards, sources included the EP's knowledge of the industries and Chinese and Western literature. For benzene, 20% of the EAs selected by a stratified random process were evaluated by two alternate methods. The study database of potential cases and controls included 18,857 jobs from the subjects' work histories. From 818 individuals initially screened as probably benzene exposed, 964 jobs underwent further review. From subjects with final diagnoses, 755 jobs qualified for inclusion in the final database for any study. For other exposures, the EA considered 17,893 jobs from 7654 subjects for possible exposures and were in the final study database. Of these, 2565 individuals had exposures of study interest from their 4909 exposed jobs. The prevalent exposures included agricultural chemicals, petroleum products, and metals. The EA involved extensive information assembly and exposure assignment by an EP and periodic reviews. The methods described went beyond those typically applied in past general population studies and may have provided improved information for the epidemiologic analyses. However, sufficient, reliable measured historical data are lacking to evaluate this conclusion.

Benzene exposure in industries using or manufacturing paint in China--a literature review, 1956-2005.

A systematic review of the Chinese literature was conducted from 1956 to 2005. The survey included both online and manual searching, as well as expert discussions aimed at providing insight into factors affecting benzene exposure levels in paint/coatings industries. Data extracted from 204 papers included: (1) year of occurrence, (2) type of paint/coatings products, (3) type of industries where the products were used or produced, (4) job titles and work activities, (5) type of literature searched, (6) working conditions whenever data were available, and (7) exposure levels. Most benzene measurements were short-term samples for comparison with the Chinese maximum allowable concentration standard. The accuracy and precision of the sampling and analytical methods were not reported. The distribution of benzene concentrations was tested and found to fit neither normal nor lognormal distributions. Analysis of variance (comparison for more than two groups) and t-test (comparison for two groups) were conducted on Blom-transformed benzene concentration data. The overall median benzene exposure levels were 215, 82, 31, and 6 mg/m(3) during the periods 1956-1978, 1979-1989, 1990-2001, and 2002-2005, respectively. Mean benzene exposure was significantly lower for paint manufacturing than paint spraying. No significant difference was found among paint types and benzene exposure for paint application. Benzene exposure was significantly higher in workplaces judged to have poor ventilation. No significant differences were found in benzene exposure as a function of industry type. Even though substantially lower when compared with levels in the past, recent benzene exposure measurements suggested that many facilities in the paint/coatings industries in China still have benzene concentrations that are above the current China occupational exposure limit for benzene (6 mg/m(3) as a time-weighted average). Benzene concentrations from the present exercise, while not directly supporting quantitative retrospective exposure estimating, provide insight on relative benzene exposure for painting tasks in the reported industries over time.

Legionnaires' disease: evaluation of a quantitative microbial risk assessment model.

BACKGROUND: The quantities of Legionella vary considerably from natural waters to water in contaminated domestic hot water supplies, whirlpool spas and cooling towers, with the risk for LD rising as the Legionella counts grow. We currently report the results from our Quantitative Microbial Risk Assessment (QMRA) model evaluation. We developed the LD QMRA model to better understand Legionella exposure risks. METHODS: Using an animal data derived model for LD, we calculated risks from estimated exposures for a whirlpool spa outbreak, two hot spring spa outbreaks and compared the results to the reported LD risks. RESULTS: The QMRA model shows agreement (generally less than an order of magnitude discrepancy) with the reported Legionnaires' disease sub-clinical severity infection, clinical severity infection, and mortality risks. CONCLUSIONS: The LD QMRA model may lead to risk based limits to supplement the current guidance on Legionella control in cooling towers, whirlpool spas and other potential exposure sources. The verification of QMRA for LD also suggests the techniques, given suitable animal model data, may be useful in quantifying human response to other airborne pathogens.

The TNF-alpha 238A polymorphism is associated with susceptibility to persistent bone marrow dysplasia following chronic exposure to benzene.

Chronic exposure to benzene can result in transient hematotoxicity (benzene poisoning, BP) or persistent bone marrow pathology including dysplasia and/or acute myeloid leukemia. We recently described a persistent bone marrow dysplasia with unique dysplastic and inflammatory features developing in individuals previously exposed to benzene (BID) [Irons RD, Lv L, Gross SA, Ye X, Bao L, Wang XQ, et al. Chronic exposure to benzene results in a unique form of dysplasia. Leuk Res 2005;29:1371-80]. In this study we investigated the association of single nucleotide polymorphisms (SNP) (-863 (C-->A), -857 (C-->T), -308 (G-->A), -238 (G-->A)) in the promoter region of the cytokine, tumor necrosis factor-alpha (TNF-alpha) on the development of BP, persistent BID and de novo myelodysplastic syndrome (MDS) in 394 individuals. Only the -238 (G-->A) polymorphism was significantly associated with the development of BID (odds ratio (OR)=7.4; 95% C.I. 1.23-44.7) and was specific for BID and not de novo MDS or BP. These findings are consistent with a role for inflammation in the development of BID and suggest that cell-specific alterations in TNF-alpha expression may promote clonal selection in the evolution of neoplastic hematopoietic disease.

Hospital-Based Case-Control Study of MDS Subtypes and Benzene Exposure in Shanghai.

OBJECTIVE: Due to the sparse data on benzene exposure and myelodysplastic syndrome (MDS) subtypes, we studied this relationship in patients from 29 hospitals in Shanghai, China. METHODS: We recruited 604 cases of MDS and 1193 controls matched on age, sex, and admission date. We interviewed subjects for information on workplace and lifestyle exposures, and developed semi-quantitative exposure estimates. RESULTS: Benzene exposure showed a direct exposure-response pattern with refractory cytopenia with multilineage dysplasia, a less certain association with refractory cytopenia with unilineage dysplasia, and no association with other MDS subtypes. A different pattern was observed with farm residence and smoking, which was primarily related to refractory anemias. CONCLUSIONS: This research demonstrates the importance of MDS subtype specification for more robust etiologic insights. Our data suggests that subtypes with non-erythroid dysplasia are associated with benzene exposure.

Chronic exposure to benzene results in a unique form of dysplasia.

Hematotoxicity following chronic benzene exposure has been recognized for over a century, although the mechanism remains unknown. We describe a novel form of bone marrow dysplasia in 23 workers exposed to high concentrations of benzene. Distinguishing features of benzene-induced dysplasia include: marked dyserythropoiesis, eosinophilic dysplasia and abnormal cytoplasmic granulation of neutrophilic precursors. Hematophagocytosis, stromal degeneration and bone marrow hypoplasia are also seen. Severe bone marrow dysplasia is frequently accompanied by clonal T cell expansion and alterations in T lymphocyte subsets. No clonal cytogenetic abnormalities were observed. These results suggest that autoimmune-mediated bone marrow injury is an early or predisposing event in the pathogenesis of benzene-induced persistent hematopoietic disease.

A hospital-based case-control study of non-Hodgkin lymphoid neoplasms in Shanghai: analysis of environmental and occupational risk factors by subtypes of the WHO classification.

The objectives were (1) to investigate potential environmental and occupational risk factors of non-Hodgkin lymphoid neoplasms (NHLN), and (2) to explore the relationships between risk factors and NHLN subtypes according to the World Health Organization (WHO) classification. The investigation was a hospital-based case-control study consisting of 649 newly diagnosed NHLN cases (August 2003 through January 2008) and 1298 individually gender-age-matched patient controls at 25 hospitals in Shanghai. A 17-page questionnaire was used to obtain information on demographics, medical history, family history, lifestyle risk factors, employment history, residential history, and occupational and non-occupational exposures. Certain occupations of interest triggered a second questionnaire, which was occupation-specific and asked for more details about jobs, tasks, materials used and work environment. Exposure assessments were based on the questionnaires, on-site workplace investigations, data published in the Chinese literature, historical exposure measurements maintained by government health agencies, and expert opinions of a panel of local scientists who were familiar with workplaces in Shanghai. Risk estimates (odds ratios and 95% confidence intervals) of individual risk factors were calculated using conditional logistic regression models. A number of potential environmental and occupational risk factors were associated with an increased risk of NHLN (all subtypes combined) and/or individual subtypes; including home/workplace renovation, living on a farm, planting crops, raising livestock or animals, farm workers, fabric sewing and cutting workers, welders and sheet metal workers, masonry and plastering workers, product and chemical testing workers, toy manufacturing, agriculture industry, and beauty salon. Exposures associated with an increased risk of NHLN (all subtypes combined) and/or individual subtypes included benzene, solvents, petroleum fuels, metals, insecticides, herbicides, fertilizers, and glues and adhesives. Multivariate models were used to adjust for potential confounding exposures, and several potential risk factors were subsequently eliminated. The results of the investigation indicated that some risk factors applied to all or most subtypes (e.g., insecticides and overall NHLN and subtypes of B-cell lymphoid neoplasms), while others to specific subtypes only (e.g., benzene and follicular lymphoma). Thus, some risk factors were subtype-specific. The difference in risk by subtype underscores the importance of the etiologic commonality and heterogeneity of NHLN subtypes.

A hospital-based case-control study of acute myeloid leukemia in Shanghai: analysis of environmental and occupational risk factors by subtypes of the WHO classification.

The objectives were: (1) to investigate potential environmental and occupational risk factors of acute myeloid leukemia (AML), and (2) to explore the relationships between risk factors and AML subtypes according to the World Health Organization (WHO) classification. The investigation was a hospital-based case-control study consisting of 722 newly diagnosed AML cases (August 2003 through June 2007) and 1444 individually gender-age-matched patient controls at 29 hospitals in Shanghai. A 17-page questionnaire was used to obtain information on demographics, medical history, family history, lifestyle risk factors, employment history, residential history, and occupational and non-occupational exposures. Certain occupations of interest triggered a second questionnaire, which was occupation-specific and asked for more details about jobs, tasks, materials used and work environment. Exposure assessments were based on the questionnaires, on-site workplace investigations, data published in the Chinese literature, historical exposure measurements maintained by government health agencies, and expert opinions of a panel of local scientists who were familiar with workplaces in Shanghai. Risk estimates (odds ratios and 95% confidence intervals) of individual risk factors were calculated using conditional logistic regression models. A number of potential environmental and occupational risk factors were associated with an increased risk of AML (all subtypes combined) and/or individual subtypes; including home or workplace renovation, living on a farm, planting crops, raising livestock or animals, farm workers, metal workers, rubber and plastic workers, wood and furniture workers, printers, loading and unloading workers, automobile manufacturing, general construction, and food and beverage industry (restaurants and other eateries). Exposures associated with an increased risk of AML (all subtypes combined) and/or individual subtypes included benzene, diesel fuel, metals, insecticides, fertilizers, glues and adhesives, paints and other coatings, and inks and pigments. Multivariate models were used to adjust for potential confounding exposures, and several potential risk factors were subsequently eliminated. The results of the investigation indicated that some risk factors applied to all or most subtypes (e.g., living on a farm and overall AML and several subtypes), while others to specific subtypes only (e.g., raising livestock and AML with multilineage dysplasia). Thus, some risk factors were subtype-specific. The difference in risk by subtype underscores the importance of the etiologic commonality and heterogeneity of AML subtypes.

A hospital-based case control study of aplastic anemia in Shanghai, China.

We report results of a hospital-based case control study of 137 consecutive patients diagnosed with aplastic anemia (AA) in participating hospitals over a 4-year period. Diagnoses were made by a single laboratory, subjects were age- and gender-matched to two controls and interviewed concerning previous disease, work histories and exposures to potential etiologic agents. Analysis was conducted on two distinct subgroups: severe aplastic anemia (SAA) and moderate aplastic anemia (MAA). In univariate regression models, the strongest associations were observed for exposure to benzene and SAA (OR=3.12, 95% CI=1.12-8.65) and life on a farm and MAA (OR=3.08, 95% CI=1.44-6.56). Benzene exposure did not show a strong dose-response relationship with either subtype. When accounting for all of the potential confounders we considered in conditional regression models, the previous relationships persisted. Other explanatory variables included hair-dye use for MAA and farm exposures, such as livestock for SAA, although most of these additional variables fell just short of statistical significance. Adjusted R-squared values were only 10% for each subtype, leaving 90% of AA occurrence unexplained. Our results suggest that: (a) benzene exposure is more strongly related to SAA than MAA, (b) farm and livestock exposures are related to both forms of AA, confirming some previous results, and (c) a large percentage of AA remains unexplained, which may indicate that individual susceptibility has a major influence on AA occurrence.

Peripheral blood effects in benzene-exposed workers.

The hematotoxic effects of benzene exposure may be important in the occurrence of subsequent health effects. We sought to provide further information on peripheral blood effects by studying 928 workers in five factories in and around Shanghai, China exposed to a wide range of benzene concentrations. Specifically, we sought to investigate which blood indices are more strongly related to benzene exposure and which concentration levels of benzene result in peripheral blood changes. Lifestyle habits and demographic information was obtained via questionnaire, and potentially important genetic influences were determined by assessing single nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene exposure estimated from individual monitoring results ranged from 0.07 to 872 mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were examined. Stronger effects on peripheral blood were seen for red cell indices such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The most sensitive parameters to benzene appeared to be neutrophils and the mean platelet volume (MPV), where effects were seen for benzene air concentrations of 7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood effects, pointing to the need to scrutinize levels of both compounds in the occupational environment.

Quantitative microbial risk assessment model for Legionnaires' disease: assessment of human exposures for selected spa outbreaks.

Evaluation of a quantitative microbial risk assessment (QMRA) model for Legionnaires' disease (LD) required Legionella exposure estimates for several well-documented LD outbreaks. Reports for a whirlpool spa and two natural spring spa outbreaks provided data for the exposure assessment, as well as rates of infection and mortality. Exposure estimates for the whirlpool spa outbreak employed aerosol generation, water composition, exposure duration data, and building ventilation parameters with a two-zone model. Estimates for the natural hot springs outbreaks used bacterial water to air partitioning coefficients and exposure duration information. The air concentration and dose calculations used input parameter distributions with Monte Carlo simulations to estimate exposures as probability distributions. The assessment considered two sets of assumptions about the transfer of Legionella from the water phase to the aerosol emitted from the whirlpool spa. The estimated air concentration near the whirlpool spa was 5 to 18 colony forming units per cubic meter (CFU/m(3)) and 50 to 180 CFU/m(3) for each of the alternate assumptions. The estimated 95th percentile ranges of Legionella dose for workers within 15 m of the whirlpool spa were 0.13-3.4 CFU and 1.3-34.5 CFU, respectively. The modeling for hot springs Spas 1 and 2 resulted in estimated arithmetic mean air concentrations of 360 and 17 CFU/m(3), respectively, and 95 percentile ranges for Legionella dose of 28 to 67 CFU and 1.1 to 3.7 CFU, respectively. The Legionella air concentration estimates fall in the range of limited reports on air concentrations of Legionella (0.33 to 190 CFU/m(3)) near showers, aerated faucets, and baths during filling with Legionella-contaminated water. These measurements may provide some indication that the estimates are of a reasonable magnitude, but they do not clarify the exposure estimates accuracy, since they were not obtained during LD outbreaks. Further research to improve the data used for the Legionella exposure assessment would strengthen the results. Several of the primary additional data needs include improved data for bacterial water to air partitioning coefficients, better accounting of time-activity-distance patterns and exposure potential in outbreak reports, and data for Legionella-containing aerosol viability decay instead of loss of capability for growth in culture.

Occupational exposure limits: an approach and calculation aid for extended work schedule adjustments.

Past reviews of occupational exposure limit (OEL) adjustments have covered both decision logic and calculation methods to derive factors to assure protection of workers on extended (also known as unusual) work shifts. The approaches reviewed included several Haber's rule based methods, several variants of single compartment toxicokinetic (TK) models, and physiologically based pharmacokinetic modeling. These models calculate OEL adjustment factors based on the work shift and the uptake and elimination of the toxicant. A key parameter of the TK models is the biologic half-life of the toxicant, but reliable data for the half-life are not available for all substances of concern. A spreadsheet is presented that implements TK calculations, with one of the presented TK calculation alternatives not dependent on half-life data. This half-life data independent approach is suggested as a viable option for situations when the toxicant's half-life is unknown or uncertain.

Using a spreadsheet to compute contaminant exposure concentrations given a variable emission rate.

Two key elements of mathematical exposure models are the contaminant's emission rate and pattern of dispersion in room air. Assuming that the mass emission rate is constant and room air is perfectly mixed affords relative mathematical simplicity. However, treating a highly variable emission rate as constant underestimates peak exposure intensity, which may be toxicologically important, and assuming a well-mixed condition underestimates exposure intensity near the source. In the past decade multizone models and turbulent diffusion models have been used to account for spatial variability in airborne concentrations, and variable emission rate functions have been described for different processes. Due to the greater complexity of these models, closed-form equations for concentration as a function of time may not be available. This article presents a numerical method that combines a variable contaminant emission rate function with the three dispersion constructs most commonly used by industrial hygienists-the well-mixed room, the near field/far field, and hemispherical turbulent eddy diffusion. The article describes how the numerical method is implemented by a computer spreadsheet program, and illustrates the method using a sinusoidal contaminant emission rate function.