Cynthia J. Hines

Improving the Health of Workers in Indoor Environments: Priority Research Needs for a National Occupational Research Agenda

Indoor nonindustrial work environments were designated a priority research area through the nationwide stakeholder process that created the National Occupational Research Agenda. A multidisciplinary research team used member consensus and quantitative estimates, with extensive external review, to develop a specific research agenda. The team outlined the following priority research topics: building-influenced communicable respiratory infections, building-related asthma/allergic diseases, and nonspecific building-related symptoms; indoor environmental science; and methods for increasing implementation of healthful building practices. Available data suggest that improving building environments may result in health benefits for more than 15 million of the 89 million US indoor workers, with estimated economic benefits of

Indoor particles and symptoms among office workers: results from a double-blind cross-over study

5 to

Mortality in the agricultural health study, 1993-2007.

75 billion annually. Research on these topics, requiring new collaborations and resources, offers enormous potential health and economic returns.

Urinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring Study

Background. We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. Methods. We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. Results. Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (−3.7%; 95% confidence limits (CL) = −6.5, −0.9). Most environmental dissatisfaction variables also improved;eg, “stuffy” air, −5.3% (95% CL = −10.3, −0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased −23.4% (95% CL = −38.1, −8.7) for every 1°C decrease. Conclusions. Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.

Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007)

Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993-1997) through 2007 to state-specific rates. To compensate for the cohorts overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMR(applicators) = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMR(spouses) = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.

Research Recommendations for Selected IARC-Classified Agents

Phthalates are used as plasticizers and solvents in industrial, medical and consumer products; however, occupational exposure information is limited. We sought to obtain preliminary information on occupational exposures to diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by analyzing for their metabolites in urine samples collected from workers in a cross-section of industries. We also obtained data on metabolites of dimethyl phthalate (DMP), benzylbutyl phthalate (BzBP), di-isobutyl phthalate and di-isononyl phthalate. We recruited 156 workers in 2003-2005 from eight industry sectors. We assessed occupational contribution by comparing end-shift metabolite concentrations to the US general population. Evidence of occupational exposure to DEHP was strongest in polyvinyl chloride (PVC) film manufacturing, PVC compounding and rubber boot manufacturing where geometric mean (GM) end-shift concentrations of DEHP metabolites exceeded general population levels by 8-, 6- and 3-fold, respectively. Occupational exposure to DBP was most evident in rubber gasket, phthalate (raw material) and rubber hose manufacturing, with DBP metabolite concentrations exceeding general population levels by 26-, 25- and 10-fold, respectively, whereas DBP exposure in nail-only salons (manicurists) was only 2-fold higher than in the general population. Concentrations of DEP and DMP metabolites in phthalate manufacturing exceeded general population levels by 4- and >1000-fold, respectively. We also found instances where GM end-shift concentrations of some metabolites exceeded general population concentrations even when no workplace use was reported, e.g. BzBP in rubber hose and rubber boot manufacturing. In summary, using urinary metabolites, we successfully identified workplaces with likely occupational phthalate exposure. Additional work is needed to distinguish occupational from non-occupational sources in low-exposure workplaces.

Comparison of Three Methods for Assessment of Hand Exposure to Azinphos-Methyl (Guthion) During Apple Thinning

Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association. Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure. Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic. Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.

Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.

Objectives There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. Data sources For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. Data extraction Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. Data synthesis Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. Conclusions Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

Captan Exposure and Evaluation of a Pesticide Exposure Algorithm among Orchard Pesticide Applicators in the Agricultural Health Study

Hand exposures of apple thinners to the pesticide azinphos-methyl (Guthion) were measured using three methods (glove, handwash, and wipe). Hand exposure sampling for each method was conducted following apple thinning work for a period of two hours for six to eight workers. Foliar residue samples were collected on each day of hand exposure sampling in the same orchard blocks that were thinned; foliar residues are considered to have been constant during the four-day study, which took place, on average, six days after pesticide application. Hand exposure estimates derived from each of the three methods differed significantly (ANOVA: p < 0.001). Mean measured exposure rates for the glove, handwash, and wipe methods were 6.48, 1.83, and 0.28 mg/hr, respectively. A corrected estimate of hand exposure, 2.7 mg/hr, was calculated from the handwash measurements and the handwash removal efficiency factor from a laboratory study. Comparison with this hand exposure estimate suggests that the glove method produced a 2.4-fold overestimate of exposure, whereas the wipe method produced a 10-fold underestimate. Studies that measure hand exposure to pesticides should include a careful description of sampling methods and should recognize the potential for measurement bias. Furthermore, the standardization and validation of dermal exposure assessment methods are critical to developing more comparable and more accurate pesticide exposure estimates.

Impact of pesticide exposure misclassification on estimates of relative risks in the Agricultural Health Study

Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.