Shelley A. Harris

Environmental immune disruptors, inflammation and cancer risk

An emerging area in environmental toxicology is the role that chemicals and chemical mixtures have on the cells of the human immune system. This is an important area of research that has been most widely pursued in relation to autoimmune diseases and allergy/asthma as opposed to cancer causation. This is despite the well-recognized role that innate and adaptive immunity play as essential factors in tumorigenesis. Here, we review the role that the innate immune cells of inflammatory responses play in tumorigenesis. Focus is placed on the molecules and pathways that have been mechanistically linked with tumor-associated inflammation. Within the context of chemically induced disturbances in immune function as co-factors in carcinogenesis, the evidence linking environmental toxicant exposures with perturbation in the balance between pro- and anti-inflammatory responses is reviewed. Reported effects of bisphenol A, atrazine, phthalates and other common toxicants on molecular and cellular targets involved in tumor-associated inflammation (e.g. cyclooxygenase/prostaglandin E2, nuclear factor kappa B, nitric oxide synthesis, cytokines and chemokines) are presented as example chemically mediated target molecule perturbations relevant to cancer. Commentary on areas of additional research including the need for innovation and integration of systems biology approaches to the study of environmental exposures and cancer causation are presented.

Occupational exposures in emergency medical service providers and knowledge of and compliance with universal precautions.

BACKGROUND Little is known about compliance with universal precautions (CUP) or occupational exposures to blood and body fluids among Emergency Medical Services (EMS) providers. The objective of this study was to obtain estimates of CUP and knowledge of universal precautions (KUP), occupational exposures, and needle and lancet sticks in the prehospital environment. METHODS A convenience sample of workers (n=311, 51% response) from 17 agencies in Virginia that provided emergency ground transportation (volunteer, commercial, government rescue squads, and fire departments) completed a questionnaire on certification and training, KUP, CUP, exposures and needlesticks, risk perceptions, and demographic variables. RESULTS Nearly all EMS providers reported exposures and were concerned about risk of HIV and hepatitis. Providers reported inconsistent CUP when treating patients or using needles, including failure to wear gloves (17%) and to appropriately dispose of contaminated materials (79%), including needles (87%), at all times. Certification type (advanced and basic) was related to both KUP and CUP. Of those respondents reporting current sharps use, 40% recapped needles. A lancet stick was reported by 1.4% (n=5), and 4.5% reported a needlestick (n=14). CONCLUSION EMS providers working in the prehospital environment experience significant exposures but are not consistently using universal precautions.

Exposure to Multiple Pesticides and Risk of Non-Hodgkin Lymphoma in Men from Six Canadian Provinces

Non-Hodgkin lymphoma (NHL) has been linked to several agricultural exposures, including some commonly used pesticides. Although there is a significant body of literature examining the effects of exposure to individual pesticides on NHL, the impact of exposure to multiple pesticides or specific pesticide combinations has not been explored in depth. Data from a six-province Canadian case-control study conducted between 1991 and 1994 were analyzed to investigate the relationship between NHL, the total number of pesticides used and some common pesticide combinations. Cases (n = 513) were identified through hospital records and provincial cancer registries and controls (n = 1,506), frequency matched to cases by age and province of residence, were obtained through provincial health records, telephone listings, or voter lists. In multiple logistic regression analyses, risk of NHL increased with the number of pesticides used. Similar results were obtained in analyses restricted to herbicides, insecticides and several pesticide classes. Odds ratios increased further when only ‘potentially carcinogenic’ pesticides were considered (OR[one pesticide] = 1.30, 95% CI = 0.90–1.88; OR[two to four] = 1.54, CI = 1.11–2.12; OR[five or more] = 1.94, CI = 1.17–3.23). Elevated risks were also found among those reporting use of malathion in combination with several other pesticides. These analyses support and extend previous findings that the risk of NHL increases with the number of pesticides used and some pesticide combinations.

Intake of Phytoestrogen Foods and Supplements Among Women Recently Diagnosed With Breast Cancer in Ontario, Canada

Phytoestrogens are found in foods such as soy (isoflavones) and flaxseed (lignans), and certain botanical supplements. Their role in estrogen receptor positive (ER+) breast cancer recurrence and treatment is controversial, and it is unknown how this affects intake among patients. The Ontario Cancer Registry was used to identify 417 population-based breast cancer cases (mean time from diagnosis was 57 days). A questionnaire was mailed to determine intake of phytoestrogen foods and supplements in the last 2 mo, changes since diagnosis and differences by ER tumor status or hormonal treatment. Of 278 (67%) respondents, 56% consumed soy foods, 39% consumed isoflavone-rich foods (tofu, soybeans, soy milk, soy nuts), and 70% ate lignan-rich foods, including flaxseed (33%). Only soy milk, flaxseed, and flaxseed bread were commonly consumed more than once/wk. Few patients (4%) took isoflavone (soy, red clover, kudzu, licorice, isoflavones) or lignan/flaxseed supplements. Since diagnosis, 17% started or stopped soy foods (most stopped); this was more prevalent among those receiving hormonal treatment (20%; 95% confidence interval (CI): 14, 26) than not (6%; 95% CI: 1, 12). No other differences by ER status or hormonal treatment were observed. Research is needed to confirm this and to explore influencing factors.

Development of models to predict dose of pesticides in professional turf applicators.

Epidemiologic studies designed to assess the chronic effects of pesticides are limited by inadequate measurements of exposures. Although cohort studies have been initiated to evaluate the effects of 2,4-dichlorophenoxyacetic acid (2,4-D) and other pesticides in professional turf applicators, they may have limited power to detect significant health risks and may be subject to bias from exposure measurement error. In this study, the doses of 2,4-D, mecoprop [2-(4-chloro-2 methylphenoxy) propionic acid, MCPP] and dicamba (3,6-dichloro-o-anisic acid) were evaluated in a group of 98 professional turf applicators from 20 companies across southwestern Ontario. During a 1-week period (Saturday to Thursday), the volume of pesticide (active ingredient) applied was only weakly related to the total dose of 2,4-D absorbed (R2=0.21). Two additional factors explained a large proportion of variation in dose: the type of spray nozzle used and the use of gloves while spraying. Individuals who used a fan-type nozzle had significantly higher doses than those who used a gun-type nozzle. Glove use was associated with significantly lower doses. Job satisfaction and current smoking influenced the dose but were not highly predictive. In the final multiple regression models predicting total absorbed dose of 2,4-D and mecoprop, approximately 63–68% of the variation was explained. The future application of these models for epidemiologic research will depend on the availability of information and records from employers, the feasibility of contacting study subjects and cost.

An analysis of factors that influence personal exposure to nitrogen oxides in residents of Richmond, Virginia

Nitrogen oxides (NOx) are ubiquitous pollutants in outdoor and indoor air. However, epidemiologic studies that evaluate health effects associated with NOx commonly rely upon outdoor concentrations of NOx, nitrogen dioxide (NO2), or residence characteristics as surrogates for personal exposure. In this study, personal exposures (48 h) and corresponding indoor and outdoor concentrations of nitric oxide (NO), NO2, and NOx were measured (July–September) in 39 adults and 9 children from 23 households in Richmond, Virginia, using Ogawa passive NOx monitors. Demographic, time–activity patterns, and household data were collected by questionnaire and used to develop exposure prediction models. Adults had higher NO2, NO, and NOx exposures (means: 16, 63, and 79 ppb, respectively) than children (13, 49, and 62 ppb). Measurements taken in bedrooms (18, 57, and 75 ppb) and living rooms (19, 65, and 84 ppb) surpassed measurements taken outdoors (15, 21, and 36 ppb). In indoor locations, NOx concentrations were influenced largely by NO, and consequently, personal exposure prediction models for NOx were reflective of models for NO. Statistical models that best predicted personal exposures included indoor measurements; outdoor measurements contributed relatively little to personal exposure. Close to 70% of the variation in personal NO2 and NOx exposure was explained by two variable models (bedroom NO2 and time spent in other indoor locations; bedroom NOx and time spent in kitchen). Given appropriate resources, measurement error in epidemiologic studies can be reduced significantly with the use of personal exposure measurements or prediction models developed from indoor measurements and survey data.

Occupational exposure to asbestos and lung cancer in men: evidence from a population-based case-control study in eight Canadian provinces

BackgroundAsbestos is classified as a human carcinogen, and studies have consistently demonstrated that workplace exposure to it increases the risk of developing lung cancer. Few studies have evaluated risks in population-based settings where there is a greater variety in the types of occupations, and exposures.MethodsThis was a population based case–control study with 1,681 incident cases of lung cancer, and 2,053 controls recruited from 8 Canadian provinces between 1994 and 1997. Self-reported questionnaires were used to elicit a lifetime occupational history, including general tasks, and information for other risk factors. Occupational hygienists, who were blinded to case–control status, assigned asbestos exposures to each job on the basis of (i) concentration (low, medium, high), (ii) frequency (<5%, 5-30%, and >30% of the time in a normal work week), and (iii) reliability (possible, probable, definite). Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI).ResultsThose occupationally exposed to (i) low, and (ii) medium or high concentrations of asbestos had ORs for lung cancer of 1.17 (95% CI=0.92 – 1.50) and 2.16 (95% CI=1.21-3.88), respectively, relative to those who were unexposed. Medium or high exposure to asbestos roughly doubled the risk for lung cancer across all three smoking pack-year categories. The joint relationship between smoking and asbestos was consistent with a multiplicative risk model.ConclusionsOur findings provide further evidence that exposure to asbestos has contributed to an increased risk of lung cancer in Canadian workplaces, and suggests that nearly 3% of lung cancers among Canadian men are caused by occupational exposure to asbestos.

National Study of Exposure to Pesticides among Professional Applicators: An Investigation Based on Urinary Biomarkers

Epidemiologic studies of pesticides have been subject to important biases arising from exposure misclassification. Although turf applicators are exposed to a variety of pesticides, these exposures have not been well characterized. This paper describes a repeated measures study of 135 TruGreen applicators over three spraying seasons via the collection of 1028 urine samples. These applicators were employed in six cities across the United States. Twenty-four-hour estimates (μg) were calculated for the parent compounds 2,4-D, MCPA, mecoprop, dicamba, and imidacloprid and for the insecticide metabolites MPA and 6-CNA. Descriptive statistics were used to characterize the urinary levels of these pesticides, whereas mixed models were applied to describe the variance apportionment with respect to city, season, individual, and day of sampling. The contributions to the overall variance explained by each of these factors varied considerably by the type of pesticide. The implications for characterizing exposures in these workers within the context of a cohort study are discussed.

Fish consumption and PCB-associated health risks in recreational fishermen on the James River, Virginia

Consumption of sport-caught fish contaminated with high levels of polychlorinated biphenyls (PCBs) may pose human health risks. To obtain estimates of fish consumption and fishing behaviors in recreational fishermen in Virginia, on-site interviews (n=143; 134 men and 9 women) were conducted at seven public boat landings along the James River. Using existing PCB concentration data from James River fish tissue samples collected from 1997, and 1999 to 2001, default and point estimates were calculated and Monte Carlo analyses conducted to estimate potential risks under different consumption scenarios. A mean of 55 fish meals/yr and 14 James River sport-caught fish (JRSCF) meals/yr were reported. Caucasians fished less often (mean of 58 d), consumed less fish (mean of 43 meals/yr) and had smaller portion sizes (mean of 11.7 oz) compared to other races combined (130 d; 82 meals/yr; and 15.6 oz). On average, respondents reported consuming 10 meals of James River catfish a year (5 kg/yr). Risk estimates produced from Monte Carlo analysis were consistently lower than the default and point estimates. Several individuals exceeded acceptable risk levels and the mean cancer and non-cancer risks among catfish consumers exceeded acceptable levels. Eighteen percent of individuals had no knowledge of fish advisories in Virginia and 4% of the subjects indicated they would consume fish under advisory. Based on reported consumption, a significant risk to recreational fishermen, as a result of consuming PCB-contaminated catfish, was found. Risks associated with consuming other species were within acceptable limits.

Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces

Pesticide exposures and immune suppression have been independently associated with the risk of non‐Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case–control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk from use of: (i) any pesticide; (ii) any organochlorine insecticide; (iii) any organophosphate insecticide; (iv) any phenoxy herbicide; (v) selected individual pesticides [1,1′‐(2,2,2‐trichloroethylidene)bis[4‐chlorobenzene]; 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl) ethane (DDT), malathion, (4‐chloro‐2‐methylphenoxy)acetic acid (MCPA), mecoprop, and (2,4‐dichlorophenoxy)acetic acid (2,4‐D); and (vi) from the number of potentially carcinogenic pesticides. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. A stratified analysis was conducted to calculate odds ratios (ORs) adjusted for age, province, proxy respondent, and diesel oil exposure. Subjects with asthma, allergies, or hay fever had non‐significantly elevated risks of NHL associated with use of MCPA (OR = 2.67, 95% confidence interval [CI]: 0.90–7.93) compared to subjects without any of these conditions (OR = 0.81, 95% CI: 0.39–1.70). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25, 95% CI: 0.69–2.26) versus subjects with none of these conditions (OR = 2.44, 95% CI: 1.65–3.61). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results.