Igor Burstyn

Studying the Determinants of Exposure: A Review of Methods

To better understand where, when, and how to control occupational exposures, it is vital that hygienists understand the factors that contribute to elevated or reduced exposure levels. Over the last two decades a burgeoning literature examining the determinants of exposure has developed, yet to date the methods used in this regard have rarely been summarized in texts or elsewhere. The purpose of this article is to provide an overview of the techniques used to study the predictors of workplace exposures. Both experimental and observational studies are examined, and the advantages and limitations of each are discussed. Fundamental study design features are reviewed. These include the selection and measurement of factors potentially related to exposure, as well as the measurement of exposure itself. Decisions reached by investigators in selecting the number of sites and workers, the number of repeated observations per worker, and the duration of sampling are discussed. Also examined are issues that commonly arise in the course of data analysis of exposure determinants. These include transformation of exposure variables, correlation of predictor variables, empirical model building, and interpretation of results. Finally, methods employed to evaluate the validity of findings are summarized.

Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks

BackgroundElectronic cigarettes (e-cigarettes) are generally recognized as a safer alternative to combusted tobacco products, but there are conflicting claims about the degree to which these products warrant concern for the health of the vapers (e-cigarette users). This paper reviews available data on chemistry of aerosols and liquids of electronic cigarettes and compares modeled exposure of vapers with occupational safety standards.MethodsBoth peer-reviewed and “grey” literature were accessed and more than 9,000 observations of highly variable quality were extracted. Comparisons to the most universally recognized workplace exposure standards, Threshold Limit Values (TLVs), were conducted under “worst case” assumptions about both chemical content of aerosol and liquids as well as behavior of vapers.ResultsThere was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures. The vast majority of predicted exposures are < <1% of TLV. Predicted exposures to acrolein and formaldehyde are typically <5% TLV. Considering exposure to the aerosol as a mixture of contaminants did not indicate that exceeding half of TLV for mixtures was plausible. Only exposures to the declared major ingredients -- propylene glycol and glycerin -- warrant attention because of precautionary nature of TLVs for exposures to hydrocarbons with no established toxicity.ConclusionsCurrent state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces. However, the aerosol generated during vaping as a whole (contaminants plus declared ingredients) creates personal exposures that would justify surveillance of health among exposed persons in conjunction with investigation of means to keep any adverse health effects as low as reasonably achievable. Exposures of bystanders are likely to be orders of magnitude less, and thus pose no apparent concern.

Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders.

Animal models indicate that maternal infection during pregnancy can result in behavioral abnormalities and neuropathologies in offspring. We examined the association between maternal inpatient diagnosis with infection during pregnancy and risk of ASD in a Swedish nationwide register-based birth cohort born 1984-2007 with follow-up through 2011. In total, the sample consisted of 2,371,403 persons with 24,414 ASD cases. Infection during pregnancy was defined from ICD codes. In the sample, 903 mothers of ASD cases (3.7%) had an inpatient diagnosis of infection during pregnancy. Logistic regression models adjusted for a number of covariates yielded odds ratios indicating approximately a 30% increase in ASD risk associated with any inpatient diagnosis of infection. Timing of infection did not appear to influence risk in the total Swedish population, since elevated risk of ASD was associated with infection in all trimesters. In a subsample analysis, infections were associated with greater risk of ASD with intellectual disability than for ASD without intellectual disability. The present study adds to the growing body of evidence, encompassing both animal and human studies, that supports possible immune-mediated mechanisms underlying the etiology of ASD.

Polycyclic aromatic hydrocarbons and fatal ischemic heart disease.

Background: Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure–response relation has not been demonstrated. Methods: We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. Results: Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m3 or higher, for which the relative risk was 1.64 (95% confidence interval = 1.13–2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. Conclusions: Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure–response relation for this association.

Increased risk of breast cancer associated with long-term shift work in Canada

Objectives Long-term night work has been suggested as a risk factor for breast cancer; however, additional studies with more comprehensive methods of exposure assessment to capture the diversity of shift patterns are needed. As well, few previous studies have considered the role of hormone receptor subtype. Methods Relationships between night shift work and breast cancer were examined among 1134 breast cancer cases and 1179 controls, frequency-matched by age in Vancouver, British Columbia, and Kingston, Ontario. Self-reported lifetime occupational histories were assessed for night shift work, and hormone receptor status obtained from tumour pathology records. Results With approximately one-third of cases and controls ever employed in night shift work, associations with duration demonstrated no relationship between either 0–14 or 15–29 years, while an association was apparent for ≥30 years (OR=2.21, 95% CI 1.14 to 4.31). This association with long-term night shift work is robust to alternative definitions of prolonged shift work, with similar results for both health and non-health care workers. Conclusions Long-term night shift work in a diverse mix of occupations is associated with increased breast cancer risk and not limited to nurses, as in most previous studies.

Maternal exposure to perfluorinated acids and fetal growth.

The widespread detection of perfluorinated acids (PFAs) in humans and known developmental toxicity in animals has raised concern about their potential effects on human reproductive health. Our objective was to determine whether increasing maternal exposure to PFAs is associated with adverse effects on fetal growth and length of gestation in women giving birth in Alberta, Canada. We examined the concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) in a cohort of 252 pregnant women who gave birth to live singletons. Each of the women had undergone an early second trimester prenatal screen, and her serum was analyzed for PFA concentrations. Data on infant and maternal variables were collected from the delivery record completed at birth. Adjusted changes in birth weight per natural log (ng/ml) of PFOA (median 1.5 ng/ml), PFHxS (median 0.97 ng/ml), and PFOS (median 7.8 ng/ml) were −37.4 g (95% confidence interval (CI): −86.0 to 11.2 g), 21.9 g (−23.4 to 67.2 g), and 31.3 g (−43.3 to 105.9 g), respectively. Mean birth weight z-score, standardized for gestational age and gender, length of gestation, and risk of preterm birth did not appear to be influenced by maternal PFA exposure. When PFA concentrations were divided into tertiles, similar patterns were observed. These results suggest that maternal PFA exposure has no substantial effect on fetal weight and length of gestation at the concentrations observed in this population.

Literature review of levels and determinants of exposure to potential carcinogens and other agents in the road construction industry

Workers in the road construction industry include asphalt plant, ground construction, and road paving workers. These individuals can be exposed to a wide range of potentially hazardous substances. A summary of levels of exposure to different substances measured during road construction is presented. In modern road paving, workers typically are exposed to 0.1 to 2 mg/m3 of bitumen fume, which includes 10 to 200 ng/m3 of benzo(a)pyrene. Sampling strategies and analytical methods employed in each reviewed survey are described briefly. The published reports provide some insight into the identity of factors that influence exposure to bitumen among road construction workers: type of work performed, meteorological conditions, temperature of paved asphalt. However, there is a lack of (a) comprehensive and well-designed studies that evaluate determinants of exposure to bitumen in road construction, and (b) standard methods for bitumen sampling and analysis. Information on determinants of other exposures in road construction is either absent or limited. It is concluded that data available through published reports have limited value in assessing historical exposure levels in the road construction industry.

Time trends (1998-2007) in brain cancer incidence rates in relation to mobile phone use in England

Mobile phone use in the United Kingdom and other countries has risen steeply since the early 1990s when the first digital mobile phones were introduced. There is an ongoing controversy about whether radio frequency (RF) exposure from mobile phones increases the risk of brain cancer. However, given the widespread use and nearly two decades elapsing since mobile phones were introduced, an association should have produced a noticeable increase in the incidence of brain cancer by now. Trends in rates of newly diagnosed brain cancer cases in England between 1998 and 2007 were examined. There were no time trends in overall incidence of brain cancers for either gender, or any specific age group. Systematic increases in rates for cancers of the temporal lobe in men (0.04 new cases/year) and women (0.02/year) were observed, along with decreases in the rates of cancers of the parietal lobe (-0.03/year), cerebrum (-0.02/year) and cerebellum (-0.01/year) in men only. The increased use of mobile phones between 1985 and 2003 has not led to a noticeable change in the incidence of brain cancer in England between 1998 and 2007. The observed increase in the rate of cancers in the temporal lobe, if caused by mobile phone use, would constitute <1 additional case per 100,000 people in that period. These data do not indicate a pressing need to implement a precautionary principle by means of population-wide interventions to reduce RF exposure from mobile phones.

A case-control study of lung cancer nested in a cohort of European asphalt workers.

Background We conducted a nested case–control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed. Objective We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers. Methods Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002–2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar. Results A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84–1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88–1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate. Conclusions We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.

Are the members of a paving crew uniformly exposed to bitumen fume, organic vapor, and benzo(a)pyrene?

The goal of this investigation was to assess if and when a crew of paving workers is uniformly exposed to bitumen fume, organic vapor, and benzo(a)pyrene. Data on paving workers with up to six repeated exposure measurements were extracted from a database of exposure measurements developed within a study of the European asphalt industry (N = 591). The uniformity of exposures to bitumen fume, organic vapor, and benzo(a)pyrene was evaluated while grouping individuals by job title, primary tasks, crew membership, and use of coal tar (discontinued in Western Europe). The estimated ranges within which 95% of individual mean exposures were expected to fall ((BW)R0.95) were used to assess exposure uniformity. Variance components were estimated by constructing mixed-effects models, with grouping variables as fixed effects and worker identity as random effect. The influence of duration of the sampling survey on estimates of exposure variability for a crew was also examined. There was a substantial variability in exposures between paving crews, as well as persons holding the same job or doing the same task, but each crew was uniformly exposed to bitumen fume and benzo(a)pyrene ((BW)R0.95 2 and 1, respectively). Workers within the same crew engaged in paving with coal tar-containing binders were not, however, uniformly exposed to benzo(a)pyrene. Also, organic vapor exposures were not uniform among the members of a paving crew ((BW)R0.95 = 15). Sampling campaigns of up to 7 months had little impact on the estimates of within- and between-worker variability. These findings should assist investigators studying paving operations in optimizing their sampling, exposure assessment, and risk evaluation protocols. The results support the notion that only empirically determined predictors of exposure can yield optimal grouping, unlike a priori grouping strategies based on general descriptors such as jobs title or tasks performed.