Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.

PURPOSE: To determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. METHODS: Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Cases (n = 316) were identified through provincial cancer registries and hospital records. Controls (n = 1,506) were frequency-matched to cases by age (± 2 years) within each province and were identified through provincial health records, telephone listings, or voter lists. The Cochran-Armitage test was used to check for trends within pesticide classes. RESULTS: Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88, 95% CI 0.92-3.87) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16, 95% CI 1.02-9.29). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47, 95% CI 1.06-5.75), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. When analyses excluded proxy respondents, OR estimates strengthened in some circumstances. CONCLUSIONS: This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens. These associations should be further evaluated, specifically in relation to age at diagnosis.

Metals in the Human Environment Strategic Network (MITHE-SN): the interface of risk assessment, public policy, and advocacy.

A 5-year strategic research network with a diverse base of industry, government, and academic partners was approved for support by National Sciences and Engineering Research Council of Canada (NSERC) on January 3, 2005. This Metals in the Human Environment Strategic Network (MITHE-SN) builds on, and further extends, science knowledge developed by the NSERC-sponsored Metals in the Environment Research Network (MITE-RN, 1999-2004). In addition to the initial award, the MITHE-SN received an additional 2-year grant specifically targeted to (1) enhance training opportunities for internships with international organizations, (2) increase international networking and linkages, and (3) optimize knowledge dissemination and technology transfer. The research program is comprised of three themes and represents a cascade of effects along food webs, from the lowest trophic levels to the highest consumers. Each of the themes addresses issues related to distinguishing the magnitudes and roles of natural background and anthropogenic metal inputs in biotic exposure to metals; estimating the bioavailable fraction of metals in the exposure media, thus better quantifying the true exposure concentration; and determining the factors that influence bioavailability of metals in media, so that predictive models can be developed for use in the development of site-specific metals criteria.

Predicting plasma concentrations of bisphenol A in children younger than 2 years of age after typical feeding schedules, using a physiologically based toxicokinetic model.

BACKGROUND: Concerns have recently been raised regarding the safety of potential human exposure to bisphenol A (BPA), an industrial chemical found in some polycarbonate plastics and epoxy resins. Of particular interest is the exposure of young children to BPA via food stored in BPA-containing packaging. OBJECTIVES: In this study we assessed the age dependence of the toxicokinetics of BPA and its glucuronidated metabolite, BPA-Glu, using a coupled BPA-BPA-Glu physiologically based toxicokinetic (PBTK) model. METHODS: Using information gathered from toxicokinetic studies in adults, we built a PBTK model. We then scaled the model to children < 2 years of age based on the age dependence of physiologic parameters relevant for absorption, distribution, metabolism, and excretion. RESULTS: We estimated the average steady-state BPA plasma concentration in newborns to be 11 times greater than that in adults when given the same weight-normalized dose. Because of the rapid development of the glucuronidation process, this ratio dropped to 2 by 3 months of age. Simulation of typical feeding exposures, as estimated by regulatory authorities, showed a 5-fold greater steady-state BPA plasma concentration in 3- and 6-month-olds compared with adults, reflecting both a reduced capacity for BPA metabolism and a greater weight-normalized BPA exposure. Because of uncertainty in defining the hepatic BPA intrinsic clearance in adults, these values represent preliminary estimates. CONCLUSIONS: Simulations of the differential BPA dosimetry between adults and young children point to the need for more sensitive analytical methods for BPA to define, with greater certainty, the adult hepatic BPA intrinsic clearance, as well as a need for external exposure data in young children.

Indirect sources of herbicide exposure for families on Ontario farms.

Although direct contact during mixing/loading, application or repair and clean-up is the major pathway by which individuals living on farms are exposed to herbicides, indirect sources such as contact with contaminated surfaces may also contribute. As part of a biomonitoring study to measure the nature and extent of exposure of farm families to herbicides, we attempted to identify potential indirect sources of exposure in a subset of 32 Ontario farms. Herbicide residues in drinking water samples as well as surface swipes of common surfaces within the home were measured and compared with urinary concentrations of the applicator, spouse and child. Residues of 2,4-dichlorophenoxyacetic acid (2,4-D) were measured on all surfaces that were tested, with the highest levels found on the washing machine knob and wash-up faucet within the home. Drinking water was not a significant source of exposure to 2,4-D for farm families. Urine samples of family members were weakly correlated with residues of 2,4-D measured on the exterior door knob. The applicators in our study, the most highly exposed subpopulation in our study group, had exposures that were less than one-third of the exposure on a daily, lifetime basis deemed to be safe by regulatory agencies in Canada and the United States. As 2,4-D residues were detected on surfaces in farm homes where 2,4-D was not reportedly used at that time, this suggests that 2,4-D applied during a previous season (or on a neighbouring farm) may be tracked into the home and persist on hard surfaces and be a chronic, albeit low level, source of exposure for family members. Pesticide applicators and their families should be counselled on hygienic practices (e.g. removing footware and washing soiled hands prior to entering the home) to reduce indirect sources of exposure. Journal of Exposure Science and Environmental Epidemiology (2006) 16, 98-104. doi:10.1038/sj.jea.7500441; published online 13 July 2005.

Biomonitoring of herbicides in Ontario farm applicators.

OBJECTIVES: Biomonitoring of pesticide residues in urine offers the advantages of integrating exposure due to all routes of entry and accounting for individual differences in several factors such as pharmacokinetics. The study was designed to measure the body burden of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) in farm applicators and to measure compliance with label recommendations regarding the use of personal protective gear and the impact of such use on exposure. METHODS: Farmers (N=126) from Ontario, Canada, collected a preexposure spot sample of urine and then two consecutive 24-hour urine samples immediately following the farmers' first use of these herbicides during 1996. Details on the pesticides used and handling practices were collected by questionnaire. RESULTS: For the farmers who reported using 2,4-D, the mean urinary concentration was 27.6 microg/l in the day-1 sample and 40.8 microg/l in the day-2 sample. The comparable figures for MCPA were 44.4 microg/l and 58.0 microg/l, respectively. Adherence to all of the recommended personal protective gear was rare (3%). Wearing goggles or a face shield during mixing and loading was associated with the lowest exposures. CONCLUSIONS: The urinary concentrations of 2,4-D and MCPA of these farm applicators were of the same order of magnitude as those published in the past decade, but lower than earlier studies, indicating that improvements in education, equipment, and labeling have likely had an impact on the degree of exposure in occupational settings.

Phenoxyacetic acid herbicide exposure for women on Ontario farms.

Women living and working on farms would be expected to have higher exposure to pesticides than the general nonoccupationally exposed population. Urinary concentrations of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and (4-chloro-2-methyl) phenoxyacetic acid (MCPA) were measured in 125 women living on farms in Ontario where these herbicides had recently been used for the first time that growing season. The women collected a spot urine void prior to the start of herbicide handling by spouses, followed by 2 consecutive 24-h urine samples. The pesticide applicator provided questionnaire data on pesticides that were used on the farm. Approximately 80% of the women had no detectable level of either herbicide in their urine. Geometric mean urinary concentrations of 2,4-D and MCPA in the d-2 samples were 0.7 microg/L. The responses to the questions on herbicide use on the farm were compared with urinary levels of the herbicide and the sensitivity for MCPA was determined to be 95-100%; however, the false positive rate for exposure was 70%. For 2,4-D, the sensitivity and specificity were approximately 70%, with a false positive rate of 30%. A simple question on whether the herbicide was used recently can accurately identify people who are likely not exposed; however, further research is required to be able to more validly predict those individuals who are exposed. Based on our study, it was concluded that exposure estimates based on questionnaire data alone may be fraught with uncertainties, which may differ depending on the particular pesticide of interest.

Farm children's exposure to herbicides: comparison of biomonitoring and questionnaire data.

BACKGROUND: Pesticide exposure has been associated with various childhood cancers. However, most studies rely on questionnaires, with few using biologic measures of dose. This study was designed to measure herbicide exposure directly in children of farm applicators, and to compare these results with exposure imputed from questionnaire information. METHODS: Two consecutive 24-hour urine samples were collected from 92 children of Ontario farm applicators who used the herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) or MCPA (4-chloro-2-methylphenoxyacetic acid) for the first time during 1996. The farm applicator completed questionnaires describing his pesticide-handling practices as well as the child's location during the various stages of handling these pesticides. RESULTS: Approximately 30% of the children on farms using these herbicides had detectable concentrations in their urine, with maximum values of 100 microg/L for 2,4-D and 45 microg/L for MCPA. Children with higher levels were more likely to be boys and to have parents who also had higher mean urinary concentrations. The sensitivity and specificity of a simple indicator of use were 47% and 72%, respectively, for 2,4-D, and 91% and 30%, respectively, for MCPA, using the biomonitoring data as the gold standard. CONCLUSIONS: Information on living on a farm, or on living on a farm where a specific pesticide is used, is not enough to classify children's exposures. Given this potential for misclassification, we urge incorporation of biomonitoring studies in subsets of children at least to estimate the extent of misclassification.

Sources, pathways, and relative risks of contaminants in surface water and groundwater: a perspective prepared for the Walkerton inquiry.

On a global scale, pathogenic contamination of drinking water poses the most significant health risk to humans, and there have been countless numbers of disease outbreaks and poisonings throughout history resulting from exposure to untreated or poorly treated drinking water. However, significant risks to human health may also result from exposure to nonpathogenic, toxic contaminants that are often globally ubiquitous in waters from which drinking water is derived. With this latter point in mind, the objective of this commission paper is to discuss the primary sources of toxic contaminants in surface waters and groundwater, the pathways through which they move in aquatic environments, factors that affect their concentration and structure along the many transport flow paths, and the relative risks that these contaminants pose to human and environmental health. In assessing the relative risk of toxic contaminants in drinking water to humans, we have organized our discussion to follow the classical risk assessment paradigm, with emphasis placed on risk characterization. In doing so, we have focused predominantly on toxic contaminants that have had a demonstrated or potential effect on human health via exposure through drinking water. In the risk assessment process, understanding the sources and pathways for contaminants in the environment is a crucial step in addressing (and reducing) uncertainty associated with estimating the likelihood of exposure to contaminants in drinking water. More importantly, understanding the sources and pathways of contaminants strengthens our ability to quantify effects through accurate measurement and testing, or to predict the likelihood of effects based on empirical models. Understanding the sources, fate, and concentrations of chemicals in water, in conjunction with assessment of effects, not only forms the basis of risk characterization, but also provides critical information required to render decisions regarding regulatory initiatives, remediation, monitoring, and management. Our discussion is divided into two primary themes. First we discuss the major sources of contaminants from anthropogenic activities to aquatic surface and groundwater and the pathways along which these contaminants move to become incorporated into drinking water supplies. Second, we assess the health significance of the contaminants reported and identify uncertainties associated with exposures and potential effects. Loading of contaminants to surface waters, groundwater, sediments, and drinking water occurs via two primary routes: (1) point-source pollution and (2) non-point-source pollution. Point-source pollution originates from discrete sources whose inputs into aquatic systems can often be defined in a spatially explicit manner. Examples of point-source pollution include industrial effluents (pulp and paper mills, steel plants, food processing plants), municipal sewage treatment plants and combined sewage-storm-water overflows, resource extraction (mining), and land disposal sites (landfill sites, industrial impoundments). Non-point-source pollution, in contrast, originates from poorly defined, diffuse sources that typically occur over broad geographical scales. Examples of non-point-source pollution include agricultural runoff (pesticides, pathogens, and fertilizers), storm-water and urban runoff, and atmospheric deposition (wet and dry deposition of persistent organic pollutants such as polychlorinated biphenyls [PCBs] and mercury). Within each source, we identify the most important contaminants that have either been demonstrated to pose significant risks to human health and/or aquatic ecosystem integrity, or which are suspected of posing such risks. Examples include nutrients, metals, pesticides, persistent organic pollutants (POPs), chlorination by-products, and pharmaceuticals. Due to the significant number of toxic contaminants in the environment, we have necessarily restricted our discussion to those chemicals that pose risks to human health via exposure through drinking water. A comprehensive and judicious consideration of the full range of contaminants that occur in surface waters, sediments, and drinking water would be a large undertaking and clearly beyond the scope of this article. However, where available, we have provided references to relevant literature to assist the reader in undertaking a detailed investigation of their own. The information collected on specific chemicals within major contaminant classes was used to determine their relative risk using the hazard quotient (HQ) approach. Hazard quotients are the most widely used method of assessing risk in which the exposure concentration of a stressor, either measured or estimated, is compared to an effect concentration (e.g., no-observed-effect concentration or NOEC). A key goal of this assessment was to develop a perspective on the relative risks associated with toxic contaminants that occur in drinking water. Data used in this assessment were collected from literature sources and from the Drinking Water Surveillance Program (DWSP) of Ontario. For many common contaminants, there was insufficient environmental exposure (concentration) information in Ontario drinking water and groundwater. Hence, our assessment was limited to specific compounds within major contaminant classes including metals, disinfection by-products, pesticides, and nitrates. For each contaminant, the HQ was estimated by expressing the maximum concentration recorded in drinking water as a function of the water quality guideline for that compound. There are limitations to using the hazard quotient approach of risk characterization. For example, HQs frequently make use of worst-case data and are thus designed to be protective of almost all possible situations that may occur. However, reduction of the probability of a type II error (false negative) through the use of very conservative application factors and assumptions can lead to the implementation of expensive measures of mitigation for stressors that may pose little threat to humans or the environment. It is important to realize that our goal was not to conduct a comprehensive, in-depth assessment of risk for each chemical; more comprehensive assessments of managing risks associated with drinking water are addressed in a separate issue paper by Krewski et al. (2001a). Rather, our goal was to provide the reader with an indication of the relative risk of major contaminant classes as a basis for understanding the risks associated with the myriad forms of toxic pollutants in aquatic systems and drinking water. For most compounds, the estimated HQs were < 1. This indicates that there is little risk associated with exposure from drinking water to the compounds tested. There were some exceptions. For example, nitrates were found to commonly yield HQ values well above 1 in- many rural areas. Further, lead, total trihalomethanes, and trichloroacetic acid yielded HQs > 1 in some treated distribution waters (water distributed to households). These latter compounds were further assessed using a probabilistic approach; these assessments indicated that the maximum allowable concentrations (MAC) or interim MACs for the respective compounds were exceeded <5% of the time. In other words, the probability of finding these compounds in drinking water at levels that pose risk to humans through ingestion of drinking water is low. Our review has been carried out in accordance with the conventional principles of risk assessment. Application of the risk assessment paradigm requires rigorous data on both exposure and toxicity in order to adequately characterize potential risks of contaminants to human health and ecological integrity. Weakness rendered by poor data, or lack of data, in either the exposure or effects stages of the risk assessment process significantly reduces the confidence that can be placed in the overall risk assessment. (ABSTRACT TRUNCATED)