Methodological issues regarding confounding and exposure misclassification in epidemiological studies of occupational exposures

Blair, Aaron; Stewart, Patricia A.; Lubin, Jay H.; Forastiére, Francesco

doi:10.1002/ajim.20281

Cited by 211 publications

(160 citation statements)

References 31 publications

Supporting

Mentioning

157

Contrasting

Order By: Relevance

“…Choosing a surrogate exposure metric (e.g., total dust) in place of a more proximal indicator (e.g., respirable-size cobalt and tungsten particles) may lead to the attenuation of observed exposure-response relationships, even in the presence of moderately high correlation (r ¼ 0.68 to 0.88) between the exposure metrics (Friesen et al, 2007). If the biologically relevant exposure is a mixture whose composition varies between work areas, as is observed for CTC dusts (Stefaniak et al, 2007), then selection of a less-specific surrogate exposure metric (e.g., cobalt alone) may bias exposure-response relationships for HMD due to exposure misclassification, despite moderately high correlation between the respirable-size cobalt and tungsten exposure constituents (Blair et al, 2007;Friesen et al, 2007). For example, Blair et al (2007) demonstrated that even moderately high correlation (rE0.7) between a surrogate and proximal exposure index may cause misclassification of up to 60% of subjects into exposure quintiles, which in turn may cause an appreciable bias in estimates of relative risk.…”

Section: Considerations For Epidemiologymentioning

confidence: 99%

Characterization of exposures among cemented tungsten carbide workers. Part I: Size-fractionated exposures to airborne cobalt and tungsten particles

Stefaniak

Virji

Day

2008

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

As many as 30,000 workers in the United States of America are exposed to cemented tungsten carbides (CTC), alloys composed primarily of tungsten carbide and cobalt, which are used in cutting tools. Inhalation of cobalt-containing particles may be sufficient for the development of occupational asthma, whereas tungsten carbide particles in association with cobalt particles are associated with the development of hard metal disease (HMD) and lung cancer. Historical epidemiology and exposure studies of CTC workers often rely only on measures of total airborne cobalt mass concentration. In this study, we characterized cobalt-and tungsten-containing aerosols generated during the production of CTC with emphasis on (1) aerosol ''total'' mass (n ¼ 252 closed-face 37 mm cassette samples) and particle size-selective mass concentrations (n ¼ 108 eight-stage cascade impactor samples); (2) particle size distributions; and (3) comparison of exposures obtained using personal cassette and impactor samplers. Total cobalt and tungsten exposures were highest in work areas that handled powders (e.g., powder mixing) and lowest in areas that handled finished product (e.g., grinding). Inhalable, thoracic, and respirable cobalt and tungsten exposures were observed in all work areas, indicating potential for co-exposures to particles capable of getting deposited in the upper airways and alveolar region of the lung. Understanding the risk of CTC-induced adverse health effects may require two exposure regimes: one for asthma and the other for HMD and lung cancer. All sizes of cobalt-containing particles that deposit in the lung and airways have potential to cause asthma, thus a thoracic exposure metric is likely biologically appropriate. Cobalt-tungsten mixtures that deposit in the alveolar region of the lung may potentially cause HMD and lung cancer, thus a respirable exposure metric for both metals is likely biologically appropriate. By characterizing size-selective and co-exposures as well as multiple exposure pathways, this series of papers offer an approach for developing biologically meaningful exposure metrics for use in epidemiology.

show abstract

Section: Considerations For Epidemiologymentioning

confidence: 99%

Characterization of exposures among cemented tungsten carbide workers. Part I: Size-fractionated exposures to airborne cobalt and tungsten particles

Stefaniak

Virji

Day

2008

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

show abstract

“…Hence, from a medical perspective, documenting exposure to multiple agents may be useful in diagnosing and managing adverse health effects. From an epidemiological perspective, even moderately high correlation (rB0.7) between surrogate and ''true'' indices of exposure may cause misclassification of up to 60% of subjects into exposure quintiles, which in turn may cause a significant bias in the relative risk estimate (Blair et al, 2007). Additionally, high correlation among the metals in terms of exposure may not necessarily correspond to high correlation with dose, as dose is very likely dependent upon the physicochemical properties and toxicokinetics of the individual metals.…”

Section: Health Implications Of Exposure Pathwaysmentioning

confidence: 99%

Characterization of exposures among cemented tungsten carbide workers. Part II: Assessment of surface contamination and skin exposures to cobalt, chromium and nickel

Day

Virji

Stefaniak

2008

J Expo Sci Environ Epidemiol

View full text Add to dashboard Cite

Cobalt, chromium and nickel are among the most commonly encountered contact allergens in the workplace, all used in the production of cemented tungsten carbides (CTC). Exposures to these metal-containing dusts are frequently associated with skin sensitization and/or development of occupational asthma. The objectives of this study were to assess the levels of cobalt, chromium and nickel on work surfaces and on workers' skin in three CTC production facilities. At least one worker in each of 26 work areas (among all facilities) provided hand and neck wipe samples. Wipe samples were also collected from work surfaces frequently contacted by the 41 participating workers. Results indicated that all surfaces in all work areas were contaminated with cobalt and nickel, with geometric means (GMs) ranging from 4.1 to 3057 mg/100 cm 2 and 1.1-185 mg/100 cm 2 , respectively; most surfaces were contaminated with chromium (GM ¼ 0.36-67 mg/100 cm 2 ). The highest GM levels of all metals were found on control panels, containers and hand tools, whereas lowest levels were on office and telecommunication equipment. The highest GM levels of cobalt and nickel on skin were observed among workers in the powder-handling facility (hands: 388 and 24 mg; necks: 55 and 6 mg, respectively). Levels of chromium on workers' skin were generally low among all facilities. Geometric standard deviations associated with surface and skin wipe measurements among work areas were highly variable. Exposure assessment indicated widespread contamination of multiple sensitizing metals in these three facilities, suggesting potential transfer of contaminants from surfaces to skin. Specific action, including improved housekeeping and training workers on appropriate use and care of personal protective equipment, should be implemented to reduce pathways of skin exposure. Epidemiologic studies of associated adverse health effects will likely require more biologically relevant exposure metrics to improve the ability to detect exposure-response relationships.

show abstract

“…Nondifferential misclassification tends to disrupt exposure-response trends and diminish a confidence that a causal association exists (Blair et al 2007). We have chosen to scale the job exposure categories from baseline.…”

Section: Discussionmentioning

confidence: 99%

Historical reconstruction of polychlorinated biphenyl (PCB) exposures for workers in a capacitor manufacturing plant

Hopf

Ruder

Waters

2013

Environ Sci Pollut Res

View full text Add to dashboard Cite

We developed a semiquantitative job exposure matrix (JEM) for workers exposed to polychlorinated biphenyls (PCBs) at a capacitor manufacturing plant from 1946 to 1977. In a recently updated mortality study, mortality of prostate and stomach cancer increased with increasing levels of cumulative exposure estimated with this JEM (trend p values=0.003 and 0.04, respectively). Capacitor manufacturing began with winding bales of foil and paper film, which were placed in a metal capacitor box (pre-assembly), and placed in a vacuum chamber for floodfilling (impregnation) with dielectric fluid (PCBs). Capacitors dripping with PCB residues were then transported to sealing stations where ports were soldered shut before degreasing, leak testing, and painting. Using a systematic approach, all 509 unique jobs identified in the work histories were rated by predetermined process-and plant-specific exposure determinants; then categorized based on the jobs' similarities (combination of exposure determinants) into 35 job exposure categories. The job exposure categories were ranked followed by a qualitative PCB exposure rating (baseline, low, medium, and high) for inhalation and dermal intensity. Category differences in other chemical exposures (solvents, etc.) prevented further combining of categories. The mean of all available PCB concentrations (1975 and 1977) for jobs within each intensity rating was regarded as a representative value for that intensity level. Inhalation (in microgram per cubic milligram) and dermal (unitless) exposures were regarded as equally important. Intensity was (1975)(1976)(1977). Such interpolations, extrapolations, and modifying factors may introduce non-differential misclassification; however, we do believe our rigorous method minimized misclassification, as shown by the significant exposure-response trends in the epidemiologic analysis. HHS Public Access

show abstract

Methodological issues regarding confounding and exposure misclassification in epidemiological studies of occupational exposures

Cited by 211 publications

References 31 publications

Characterization of exposures among cemented tungsten carbide workers. Part I: Size-fractionated exposures to airborne cobalt and tungsten particles

Characterization of exposures among cemented tungsten carbide workers. Part I: Size-fractionated exposures to airborne cobalt and tungsten particles

Characterization of exposures among cemented tungsten carbide workers. Part II: Assessment of surface contamination and skin exposures to cobalt, chromium and nickel

Historical reconstruction of polychlorinated biphenyl (PCB) exposures for workers in a capacitor manufacturing plant

Contact Info

Product

Resources

About