Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD.

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods. We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008-2012). OPEs were measured in house dust sampled at 3-4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (ß: 0.63%, 95% CI: -0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum. We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.

Indoor exposure to phthalates and polycyclic aromatic hydrocarbons (PAHs) to Canadian children: the Kingston allergy birth cohort.

BACKGROUND: Canadian children are widely exposed to phthalates and polycyclic aromatic hydrocarbons (PAHs) from indoor sources. Both sets of compounds have been implicated in allergic symptoms in children. OBJECTIVE: We characterize concentrations of eight phthalates and 12 PAHs in floor dust from the bedrooms of 79 children enrolled in the Kingston Allergy Birth Cohort (KABC). METHOD: Floor dust was collected from the bedrooms of 79 children who underwent skin prick testing for common allergens after their first birthday. Data were collected on activities, household, and building characteristics via questionnaire. RESULTS: Diisononyl phthalate (DiNP) and phenanthrene were the dominant phthalate and PAH with median concentrations of 561 µg/g and 341 ng/g, respectively. Benzyl butyl phthalate (BzBP) and chrysene had the highest variations among all tested homes, ranging from 1-95% to 1-99%, respectively. SIGNIFICANCE: Some phthalates were significantly associated with product and material use such as diethyl phthalate (DEP) with fragranced products and DiNP and DiDP with vinyl materials. Some PAHs were significantly associated with household characteristics, such as benzo[a]pyrene with smoking, and phenanthrene and fluoranthene with the presence of an attached garage. Socioeconomic status (SES) had positive and negative relationships with some concentrations and some explanatory factors. No significant increases in risk of atopy (positive skin prick test) was found as a function of phthalate or PAH dust concentrations.

Early life exposure to phthalates and the development of childhood asthma among Canadian children.

BACKGROUND: Studies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life. OBJECTIVE: To investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms. METHODS: This study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (ntotal = 129) and recurrent wheeze between 2 and 5 years (ntotal = 332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms. RESULTS: Di(2-ethylhexyl) phthalate (DEHP) had the highest concentration in dust (mediansubcohort = 217 µg/g), followed by benzyl butyl phthalate (BzBP) (20 µg/g). A nearly four-fold increase in risk of developing asthma was associated with the highest concentration quartile of DEHP (OR = 3.92, 95% CI: 1.87-8.24) including a positive dose-response relationship. A two-fold increase in risk of recurrent wheeze was observed across all quartiles compared to the lowest quartile of DEHP concentrations. Compared to other wheeze subtypes, stronger associations for DEHP were observed with the late onset wheezing subtype, while stronger associations for di-iso-butyl phthalate (DiBP) and BzBP were observed with the transient subtype. DISCUSSION: DEHP exposure at 3-4 months, at concentrations lower than other studies that reported an association, were associated with increased risks of asthma and recurrent wheeze among children at 5 years. These findings suggest the need to assess whether more stringent regulations are required to protect children's health, which can be informed by future work exploring the main sources of DEHP exposure.

Early life exposure to phthalates in the Canadian Healthy Infant Longitudinal Development (CHILD) study: a multi-city birth cohort.

BACKGROUND: Few studies have examined phthalate exposure during infancy and early life, critical windows of development. The Canadian Healthy Infant Longitudinal Development (CHILD) study, a population-based birth cohort, ascertained multiple exposures during early life. OBJECTIVE: To characterize exposure to phthalates during infancy and early childhood. METHODS: Environmental questionnaires were administered, and urine samples collected at 3, 12, and 36 months. In the first 1578 children, urine was analyzed for eight phthalate metabolites: mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-3-carboxypropyl phthalate (MCPP). Geometric mean (GM) concentrations were calculated by age, together with factors that may influence concentrations. Trends with age were examined using mixed models and differences within factors examined using ANOVA. RESULTS: The highest urinary concentration was for the metabolite MBP at all ages (GM: 15-32 ng/mL). Concentrations of all phthalate metabolites significantly increased with age ranging from GM: 0.5-15.1 ng/mL at 3 months and 1.9-32.1 ng/mL at 36 months. Concentrations of all metabolites were higher in the lowest income categories except for MEHP at 3 months, among children with any breastfeeding at 12 months, and in urine collected on dates with warmer outdoor temperatures (>17 °C), except for MBzP at 3 months and MEHP at 3 and 12 months. No consistent differences were found by gender, study site, or maternal age. CONCLUSIONS: Higher phthalate metabolite concentrations were observed among children in lower income families. Examination of factors associated with income could inform interventions aimed to reduce infant phthalate exposure.

Uncertainties associated with assessing Ontario uranium miners' exposure to radon daughters.

The Ontario uranium miners study is a large (n = 28 546) cohort with low levels of radon exposure relative to other uranium miner cohorts. Multiple methods were used over time to estimate annual occupational exposure to radon daughters including: mine-specific extrapolations by mining engineers, area sampling in limited areas of the mines combined with approximate working time and lastly, consistent exposure sampling in different locations of the mine combined with workers' time cards. Nonetheless, estimating exposures involves assumptions that lead to some uncertainty in occupational exposure characterisation arising from the assessment approach and variability within workplace, over time and by individual. An evaluation of the total uncertainty associated with radon daughter exposure estimation in Ontario miners over time has not been conducted. The objective of this study was to identify the contributing sources and assess the total uncertainty associated with estimating occupational radon daughter exposure among underground Ontario uranium miners over the course of uranium mining. The five sources of radon daughter exposure uncertainty evaluated were: natural variations in radon concentration, estimation of working time, precision of the radon measurement method, unintended errors during sampling, and record keeping and transcription of exposure data. These sources were examined separately for the period 1958 to 1967 and then 1968 onward due to changes in radon daughter concentration measurement practices between these periods. The magnitude of uncertainty associated with each of these sources over time were determined by reviewing historical literature on uranium mining in Ontario as well as through expert advice. Using the root sum square method, the total radon daughter exposure uncertainty was found to be 53 to 67% in the earlier period of uranium mining from 1958 to 1967. This decreased to 31 to 39% for the period 1968 to 1996 with natural variations of radon daughter concentrations in mines accounting for the largest percentage of uncertainty. This assessment provides an initial step in understanding the effect of exposure uncertainty on risk estimates. The impact of this uncertainty on the dose-response relationship between radon exposure and cancer risk will be assessed in future work.

Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners.

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with cumulative radon exposure; compared to the reference group (<1 cumulative working level months (WLM)), the highest exposure category (>60 cumulative WLM) had a relative risk (RR) of 2.76 (95% CI: 1.67⁻4.57). Adenocarcinoma had the lowest risk and was not significantly associated with exposure to radon decay products (RR = 1.49, 95% CI: 0.96⁻2.31). An increasing, linear trend in relative risk was noted with increasing cumulative WLM across small cell, squamous cell, and large cell lung carcinomas (Ptrend < 0.05). Similarly, the excess relative risk (ERR) per WLM was highest for small cell lung carcinoma (ERR/WLM = 0.15, p < 0.01), followed by squamous cell carcinoma (ERR/WLM = 0.12, p < 0.01). Non-statistically significant excess risk was observed for adenocarcinoma (ERR/WLM = 0.004, p = 0.07). Our analysis of the Ontario Uranium Miners cohort data shows differences in the magnitude of the risks across four histological subtypes of lung carcinoma; the strongest association was noted for small cell lung carcinoma, followed by squamous cell, large cell, and lastly adenocarcinoma, which showed no significant associations with exposure to radon decay products.

Cancer incidence and mortality from exposure to radon progeny among Ontario uranium miners.

OBJECTIVES: The study objectives were to extend the follow-up of the Ontario uranium miners cohort, one of the largest cohorts of uranium miners with low cumulative exposures, to examine the relationship between radon exposure and lung cancer mortality and, for the first time incidence, and address gaps in the literature, including dose-response relationship between radon exposure and other cancer sites, and non-cancer mortality. METHODS: The cohort of mine and mill workers was created using data from Canada's National Dose Registry and the Ontario Mining Master File. The follow-up for the cohort was recently extended for mortality (1954-2007) and for the first time includes cancer incidence (1969-2005). The Poisson regression was used to estimate relative risks (RR) and excess relative risks (ERR) and their 95% CIs with levels of cumulative radon exposure. RESULTS: The cohort consisted of 28 546 male miners with a mean cumulative radon exposure of 21.0 working level months (WLM). An increased risk of lung cancer and a dose-response relationship was observed with cumulative radon exposure. Miners exposed to >100 WLM demonstrated a twofold increase in the risk of lung cancer incidence (RR=1.89, CI 1.43 to 2.50) compared with the non-exposed group, and a linear ERR of 0.64/100 WLM (CI 0.43 to 0.85), with similar results observed for mortality. No association was observed for other cancer sites (stomach, leukaemia, kidney and extrathoracic airways) or non-cancer sites (cardiovascular diseases) with increasing cumulative exposure to radon. CONCLUSIONS: These findings suggest no increased risk of cancer sites other than lung or non-cancer mortality from relatively low cumulative exposure to radon.

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.