Michèle Bouchard

Université de Montréal, Montréal, Quebec, Canada

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Publications (75)164.52 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Diabetes rising prevalence is of great concern in Africa because of its socio-economic impacts in a context of limited access to health care. The inappropriate use of pesticides may add to the burden of diabetes in Africa. The present study was carried out in a cotton producing area of Benin in order to assess the relationship between the highest prevalence of diabetes observed in the country and organochlorine pesticide (OCP) exposure. Methods: A case-control study was conducted in 2011. A sample of 106 subjects with diabetes and 106 non-diabetic controls were paired by age, gender, ethnicity and residential area. Personal and socioeconomic information, along with anthropometric measurements were collected. Blood samples were assayed for total lipids and 14 OCPs by gas-chromatography coupled with mass-spectrometry. Data were recorded for the four detectable OCPs: p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE), p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), β -hexachlorocyclohexane (β-HCH), and trans-nonachlor. Results: Serum levels of all four detected OCPs were consistently higher in diabetic subjects than in non-diabetic controls. The odds ratio of diabetes was nearly three-fold higher when comparing the third tertile of p,p’-DDE and p,p’-DDT and β-HCH levels with the first tertile, without adjustment for potential confounders. The association remained significant for p,p’-DDT (OR = 2.59; 95% CI: 1.17-5.42) and p,p’-DDE (OR = 2.11; 95% CI: 1.01-4.54) after adjusting for a family history of diabetes, abdominal obesity, and wealth index or education. Conclusion: Our data showed that exposure to p,p’-DDT and p,p’-DDE was associated with an increased risk of diabetes. These findings have major public health implications.
    Journal of Environmental and Occupational Science. 07/2014; 3(3):121-129.
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    ABSTRACT: The Borgou region of northern Benin is a major cotton producing area and consistently uses higher amounts of pesticides than other areas of the country. Organochlorine pesticides (OCPs), poorly handled, have been widely used and are still illegally present. We therefore hypothesized that serum OCP levels would be high in Borgou. As part of a case-control study on diabetes status and pesticide exposure, we measured the distribution of serum concentrations of 14 OCPs by gas chromatography with mass spectrometry. A sample of 118 diabetic subjects was selected using a four-stage cluster sampling with 54.2% of men and 45.8% of women; 43% lived in urban areas, 14.4% were obese and 39.8% had high economic status. The four detected OCPs were p,p'-DDT, p,p'-DDE, β-HCH and trans-nonachlor with respective geometric means (geometric standard deviation) of 497.1 (4.5), 20.6 (7.9), 2.9 (3.4), and 2.0 (2.3) ng/g of total serum lipids. OCP levels were significantly higher in obese, wealthier and more educated subjects and in those living in urban areas as compared to the other groups, particularly for p,p'-DDE, p,p'-DDT and β-HCH. Levels of DDT and DDE were higher than reported in other countries where DDT is no longer permitted. The low DDT/DDE ratio of 0.05 suggests past human exposure through food contamination. There is thus a need to reinforce governmental regulations for a more responsible use of pesticides in the country, in order to reduce health risks associated with persistent organic pollutants.
    Environment international 04/2014; 69C:1-8. · 6.25 Impact Factor
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    ABSTRACT: To assess exposure to pyrethroids in the general population, one of most widely used method nowadays consists of measuring urinary metabolites. Unfortunately, interpretation of data is limited by the unspecified relation between dose and levels in biological tissues and excreta. The objective of this study was to develop a common multi-compartment toxicokinetic model to predict the time courses of two mainly used pyrethroid pesticides, permethrin and cypermethrin, and their metabolites (cis-DCCA, trans-DCCA and 3-PBA) in the human body and in accessible biological matrices following different exposure scenarios. Toxicokinetics was described mathematically by systems of differential equations to yield the time courses of these pyrethroids and their metabolites in the different compartments. Unknown transfer rate values between compartments were determined from best fits to available human data on the urinary excretion time courses of metabolites following an oral and dermal exposure to cypermethrin in volunteers. Since values for these coefficients have not yet been determined, a mathematical routine was programmed in MathCad to establish the possible range of values on the basis of physiological and mathematical considerations. The best combination of parameter values was then selected using a statistic measure (reliability factor) along with a statistically acceptable range of values for each parameter. With this approach, simulations provided a close approximation to published time course data. This model allows to predict urinary time courses of trans-DCCA, cis-DCCA and 3-PBA, whatever the exposure route. It can also serve to reconstruct absorbed doses of permethrin or cypermethrin in the population using measured biomarker data.
    PLoS ONE 02/2014; 9(2):e88517. · 3.53 Impact Factor
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    ABSTRACT: Biomathematical modeling has become an important tool to assess xenobiotic exposure in humans. In the present study, we have used a human physiologically-based pharmacokinetic (PBPK) model and an simple compartmental toxicokinetic model of benzo(a)pyrene (BaP) kinetics and its 3-hydroxybenzo(a)pyrene (3-OHBaP) metabolite to reproduce the time-course of this biomarker of exposure in the urine of industrially exposed workers and in turn predict the most plausible exposure scenarios. The models were constructed from in vivo experimental data in rats and then extrapolated from animals to humans after assessing and adjusting the most sensitive model parameters as well as species specific physiological parameters. Repeated urinary voids from workers exposed to polycyclic aromatic hydrocarbons (PAHs) have been collected over the course of a typical workweek and during subsequent days off work; urinary concentrations of 3-OHBaP were then determined. Based on the information obtained for each worker (BaP air concentration, daily shift hours, tasks, protective equipment), the time courses of 3-OHBaP in the urine of the different workers have been simulated using the PBPK and toxicokinetic models, considering the various possible exposure routes, oral, dermal and inhalation. Both models were equally able to closely reproduce the observed time course of 3-OHBaP in the urine of workers and predicted similar exposure scenarios. Simulations of various scenarios suggest that the workers under study were exposed mainly by the dermal route. Comparison of measured air concentration levels of BaP with simulated values needed to obtain a good approximation of observed time course further pointed out that inhalation was not the main route of exposure for most of the studied workers. Both kinetic models appear as a useful tool to interpret biomonitoring data of PAH exposure on the basis of 3-OHBaP levels.
    PLoS ONE 01/2014; 9(7):e102570. · 3.53 Impact Factor
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    ABSTRACT: The Borgou region of northern Benin is a major cotton producing area and consistently uses higher amounts of pesticides than other areas of the country. Organochlorine pesticides (OCPs), poorly handled, have been widely used and are still illegally present. We therefore hypothesized that serum OCP levels would be high in Borgou. As part of a case–control study on diabetes status and pesticide exposure, we measured the distribution of serum concentrations of 14 OCPs by gas chromatography with mass spectrometry. A sample of 118 diabetic subjects was selected using a four-stage cluster sampling with 54.2% of men and 45.8% of women; 43% lived in urban areas, 14.4% were obese and 39.8% had high economic status. The four detected OCPs were p,p′-DDT, p,p′-DDE, β-HCH and trans-nonachlor with respective geometric means (geometric standard deviation) of 497.1 (4.5), 20.6 (7.9), 2.9 (3.4), and 2.0 (2.3) ng/g of total serum lipids. OCP levels were significantly higher in obese, wealthier and more educated subjects and in those living in urban areas as compared to the other groups, particularly for p,p′-DDE, p,p′-DDT and β-HCH. Levels of DDT and DDE were higher than reported in other countries where DDT is no longer permitted. The low DDT/DDE ratio of 0.05 suggests past human exposure through food contamination. There is thus a need to reinforce governmental regulations for a more responsible use of pesticides in the country, in order to reduce health risks associated with persistent organic pollutants.
    Environment International. 01/2014; 69:1–8.
  • Nolwenn Noisel, Gaétan Carrier, Michèle Bouchard
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    ABSTRACT: Biomonitoring is increasingly used to assess exposure to selenium (Se) in the population. However, there is little harmonization among protocols used in the different studies (varying biological matrices, differences in expression of results (concentrations versus amounts, units)). This makes inter-comparison of biomonitoring results across studies difficult. From a public health risk perspective, it also becomes challenging to estimate baseline levels in biological matrices for populations exposed by various sources. The aim of this study was thus to perform a systematic analysis of the relationship between Se intakes and biological concentrations based on published data. Inclusion and exclusion criteria were used and led to select 75 published biomonitoring data in humans from an extended review of Se biomonitoring studies. This represents 8 628 individuals who provided biological samples aiming at documenting Se exposure and/or Se concentrations in two or more biological matrices. Mathematical algorithms that relate Se intakes to biological concentrations and establish matrix-to-matrix associations were derived from these pooled biomonitoring data. Logarithmic regressions showed good correlations between Se intakes and whole blood concentrations (R2 = 0.884), plasma concentrations (R2 = 0.863) and urinary excretion rates (R2 = 0.958). Blood and plasma concentrations were also strongly related (R2 = 0.874), as were whole blood concentrations and urinary excretion rates (R2 = 0.953). The interpretation of the log-regression coefficients allowed illustrating Se physiology. Se concentrations in plasma tend to plateau when daily intake exceed 150 μg/d, whereas Se in urine increases rapidly above this threshold. The application of the algorithms to other independent data sets in order to reconstruct past Se intakes confirmed that interpretation of results on the basis of Se in integuments may be misleading if external contamination is not avoided. This approach based on pooled data covered a wide range of exposure and the large number of data integrated increased the level of confidence of results.
    International Journal of Hygiene and Environmental Health. 01/2014;
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    ABSTRACT: Drinking water intake of arsenic (As) from private wells may represent a significant exposure pathway and induce oxidative DNA damage. We measured total As concentrations in hair and nails, and concentrations of the different species of As and its metabolites as well as 8-OHdG in urine of 110 non-smoking adults living in a rural region of the Province of Quebec, Canada. Significant differences in exposure biomarker levels were observed between individuals consuming drinking water with As levels of≤1.0,>1.0 -≤10 and>10 μg/l. Multivariate linear regression analysis also showed a significant relationship between estimated daily drinking water intakes of As and biomarker levels. Conversely, 8-OHdG levels were not significantly related to daily drinking water intakes of As or to hair, nail or urinary exposure biomarker levels, according to multivariate linear regression analysis. Even at the relatively low levels of As found in well water of our participants, water consumption significantly increases their body load of As, as confirmed by multiple matrix measurements, which reflected exposure over different time frames. However, this increased internal As dose was not associated with higher oxidative damage to DNA as reflected by urinary 8-OHdG levels.Journal of Exposure Science and Environmental Epidemiology advance online publication, 6 November 2013; doi:10.1038/jes.2013.80.
    Journal of Exposure Science and Environmental Epidemiology 11/2013; · 3.19 Impact Factor
  • Naïma El Majidi, Michèle Bouchard, Gaétan Carrier
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    ABSTRACT: The impact polychlorinated biphenyl (PCB) exposure on thyroid status in pregnant women and newborns was investigated in various epidemiological studies, but findings show inconsistencies, and differences in biological indicators of exposure between studies limits comparison of results. The aim of this research was to use a procedure previously developed to standardize PCB biological concentration data between published studies to perform a systematic analysis of associations between PCB exposure and thyroid hormones (THs) (total and free T3 and T4) or thyroid stimulating hormone (TSH) in pregnant women and newborns. Biological concentrations from nineteen studies were expressed in total PCB equivalent per kg of lipids in maternal plasma (μgPCBMPEQkg(-1) lipids). Systematic analysis of the "standardized biological concentration-thyroid parameters" relationship was conducted through the application of methodological criteria in both pregnant women and newborns. Standardization of PCB levels and application of methodological criteria led to assign higher confidence to ten of the reviewed studies. Among the retained studies in pregnant women, only one reported a significant association between PCBs and total T3 levels, but no association were observed when circulating TSH and free T4 levels were used to assess thyroid function. Regarding the association between prenatal PCB exposure and thyroid status in newborns, a lack of significant association was consistently obtained in the retained studies assigned an overall high confidence. The weight of evidence of a significant impact of PCB exposure on TSH and TH levels at the described biological levels in pregnant women and newborns (mean<1000μgPCBMPEQkg(-1) lipids) appears low according to this systematical analysis.
    Chemosphere 11/2013; · 3.14 Impact Factor
  • Roberto Heredia-Ortiz, Michèle Bouchard
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    ABSTRACT: 3-Hydroxybenzo(a)pyrene (3-OHBaP) in urine has been proposed as a biomarker of occupational exposure to polycyclic aromatic hydrocarbons. However, to reconstruct exposure doses in workers from biomarker measurements, a thorough knowledge of the kinetics of the benzo(a)pyrene (BaP) and 3-OHBaP given different routes of exposure is needed. A rat physiologically-based pharmacokinetic model of BaP and 3-OHBaP was built. Organs (tissues) represented as compartments were based on in vivo experimental data in rats. Tissue: blood partition coefficients, permeability coefficients, metabolism rates, excretion parameters, and absorption fractions and rates for different routes-of-entry were obtained directly from published in vivo time courses of BaP and 3-OHBaP in blood, various tissues and excreta of rats. The latter parameter values were best-fitted by least square procedures and Monte Carlo simulations. Sensitivity analyses were then carried out to ensure the stability of the model and the key parameters driving the overall modeled kinetics. This modeling pointed out critical determinants of the kinetics: (1) hepatic metabolism of BaP and 3-OHBaP elimination rate as the most sensitive parameters; (2) the strong partition of BaP in lungs compared to other tissues, followed by adipose tissues and liver; (3) the strong partition of 3-OHBaP in kidneys; (4) diffusion-limited tissue transfers of BaP in lungs and 3-OHBaP in lungs, adipose tissues and kidneys; (5) significant entero-hepatic recycling of 3-OHBaP. Very good fits to various sets of experimental data in rats from four different routes-of-entry (intravenous, oral, dermal and inhalation) were obtained with the model.
    Journal of Pharmacokinetics and Biopharmaceutics 10/2013; · 2.06 Impact Factor
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    Pierre Brochu, Michèle Bouchard, Sami Haddad
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    ABSTRACT: Physiological daily inhalation rates reported in our previous study for normal-weight subjects 2.6-96 years old were compared to inhalation data determined in free-living overweight/obese individuals (n = 661) aged 5-96 years. Inhalation rates were also calculated in normal-weight (n = 408), overweight (n = 225), and obese classes 1, 2, and 3 adults (n = 134) aged 20-96 years. These inhalation values were based on published indirect calorimetry measurements (n = 1,069) and disappearance rates of oral doses of water isotopes (i.e., (2) H2 O and H2 (18) O) monitored by gas isotope ratio mass spectrometry usually in urine samples for an aggregate period of over 16,000 days. Ventilatory equivalents for overweight/obese subjects at rest and during their aggregate daytime activities (28.99 ± 6.03 L to 34.82 ± 8.22 L of air inhaled/L of oxygen consumed; mean ± SD) were determined and used for calculations of inhalation rates. The interindividual variability factor calculated as the ratio of the highest 99th percentile to the lowest 1st percentile of daily inhalation rates is higher for absolute data expressed in m(3) /day (26.7) compared to those of data in m(3) /kg-day (12.2) and m(3) /m(2) -day (5.9). Higher absolute rates generally found in overweight/obese individuals compared to their normal-weight counterparts suggest higher intakes of air pollutants (in μg/day) for the former compared to the latter during identical exposure concentrations and conditions. Highest absolute mean (24.57 m(3) /day) and 99th percentile (55.55 m(3) /day) values were found in obese class 2 adults. They inhale on average 8.21 m(3) more air per day than normal-weight adults.
    Risk Analysis 10/2013; · 2.28 Impact Factor
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    ABSTRACT: The diabetes burden is growing in Sub-Saharan Africa (SSA). The low overall access to health care has been documented to contribute to the high diabetes-related mortality. Due to economic, demographic, epidemiological and nutrition transitions in SSA, the growing prevalence of diabetes appears to be related to obesogenic lifestyles and the intergenerational impact of malnutrition in women of childbearing age. Both overnutrition and undernutrition have been associated with the development of diabetes and other chronic diseases. Africans are also suspected of being genetically predisposed to diabetes. According to existing data in developed countries, exposure to pesticides, particularly organochlorines and metabolites, is associated with a higher risk of developing type 2 diabetes and its comorbidities. In African countries, pesticide exposure levels often appear much higher than in developed countries. Furthermore, undernutrition, which is still highly prevalent in SSA, could increase susceptibility to the adverse effects of organic pollutants. Therefore, the growing and inadequate use of pesticides may well represent an additional risk factor for diabetes in SSA. Additionally, high exposure to pesticides in African infants in utero and during the perinatal period may increase the intergenerational risk of developing diabetes in SSA.
    Current diabetes reviews 08/2013;
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    ABSTRACT: Acrylamide (AA) is a probable human carcinogen found in several foods. Little information is available regarding exposure of adolescents, a subgroup potentially consuming more AA-rich foods. We investigated the relationship between dietary AA intake and levels of biomarkers of exposure (urinary metabolites and hemoglobin adducts) in 195 non-smoking teenagers of Montreal Island aged 10-17 years. Dietary habits and personal characteristics were documented by questionnaire. AA and its metabolites were quantified in 12-h urine collections by LC-MS/MS. Hemoglobin adducts from 165 blood samples were also analyzed by LC-MS/MS. Most prevalent urinary metabolites were NACP and NACP-S, with respective geometric mean concentrations of 31.2 and 14.2 μmol/mol creatinine. Geometric mean concentrations of AAVal and GAVal (hemoglobin adducts of AA and glycidamide (GA) with N-terminal valine residues) were 45.4 and 45.6 pmol/g globin, respectively. AA intake during the 2 days before urine collection was a significant predictor of NACP+NACP-S urinary concentrations (P<0.0001). AA intakes during the month before blood collection (P<0.0001) and passive smoking (P<0.05) were associated with adduct levels. Levels of hemoglobin adducts were above biomonitoring equivalent values corresponding to a 1 × 10(-4) excess cancer risk, which may indicate the need to reduce AA exposure in the population.Journal of Exposure Science and Environmental Epidemiology advance online publication, 12 June 2013; doi:10.1038/jes.2013.34.
    Journal of Exposure Science and Environmental Epidemiology 06/2013; · 3.19 Impact Factor
  • Naïma El Majidi, Michèle Bouchard, Gaétan Carrier
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    ABSTRACT: Impact of prenatal exposure to polychlorinated biphenyls (PCBs) on mental and motor development has been investigated in various children cohorts, but findings show temporal inconsistencies. Because a direct comparison of results obtained from different cohorts remains difficult, temporal relationship between biological PCB concentrations and long-term developmental effects is still not clearly established. The objective of this research was to use a procedure previously developed to standardize PCB biological concentration data across cohorts in order to perform a systematic analysis of temporal associations between prenatal PCB exposure and mental and motor development from neonatal period (or a young age) until school age. Prenatal exposure data from nine cohorts were standardized in terms of total PCBs per kg of lipids in maternal plasma. Systematic analysis of the "standardized biological concentration - development" relationship during follow-up of each cohort was then conducted through the application of Hill criteria. This led to retain six of the studied cohorts in the final analysis. A biological level of prenatal PCB exposure below which risk of mental or motor development should be negligible was established in the order of 1000 μg/kg of lipids in maternal plasma.
    Regulatory Toxicology and Pharmacology 03/2013; · 2.13 Impact Factor
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    ABSTRACT: The distribution of acrylamide in food items frequently consumed by Canadian adolescents was determined along with estimates of their contribution to the overall dietary intake of acrylamide. A total of 196 non-smoking adolescents (10-17 years old) were recruited in Montreal Island population, Canada. Participants were invited to fill out a 2-day food diary and a food frequency questionnaire over the last month. 146 samples of foods most frequently consumed by participants were analyzed for acrylamide contents. The highest acrylamide contents were measured in deep-fried french fries and potato chips (mean ± SD: 1053 ± 657 and 524 ± 276 ng/g respectively). On the basis of the 2-day food diary, median total daily intake of acrylamide was estimated at 0.29 μg/kg b.w./d, as compared to 0.17 μg/kg b.w./d on the basis of the food frequency questionnaire. These values are similar to those reported in comparable populations. Deep-fried french fries consumption contributed the most to daily acrylamide intake (50%) followed by potato chips (10%), oven-baked french fries (8%) and breakfast cereals (8%). Margins of exposure based on genotoxic benchmark dose limits were estimated to be low (≈<100) in high-consumer adolescents, indicating the need to continue efforts to reduce dietary acrylamide exposure.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 03/2013; · 2.99 Impact Factor
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    ABSTRACT: Interactions between nanoparticles (NP), humans and the environment are not fully understood yet. Moreover, frameworks aiming at protecting human health have not been adapted to NP but are nonetheless applied to NP-related activities. Consequently, business organizations currently have to deal with NP-related risks despite the lack of a proven effective method of risk-management. To respond to these concerns and fulfill the needs of populations and industries, ÉquiNanos was created as a largely interdisciplinary provincial research team in Canada. ÉquiNanos consists of eight platforms with different areas of action, from adaptive decision-aid tool to public and legal governance, while including biological monitoring. ÉquiNanos resources aim at responding to the concerns of the Quebec nanotechnology industry and public health authorities. Our mandate is to understand the impact of NP on human health in order to protect the population against all potential risks emerging from these high-priority and rapidly expanding innovative technologies.
    Nanomedicine: nanotechnology, biology, and medicine 09/2012; · 6.93 Impact Factor
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    ABSTRACT: Exposure to various pesticides has been characterized in workers and the general population, but interpretation and assessment of biomonitoring data from a health risk perspective remains an issue. For workers, a Biological Exposure Index (BEI®) has been proposed for some substances, but most BEIs are based on urinary biomarker concentrations at Threshold Limit Value - Time Weighted Average (TLV-TWA) airborne exposure while occupational exposure can potentially occurs through multiple routes, particularly by skin contact (i.e.captan, chlorpyrifos, malathion). Similarly, several biomonitoring studies have been conducted to assess environmental exposure to pesticides in different populations, but dose estimates or health risks related to these environmental exposures (mainly through the diet), were rarely characterized. Recently, biological reference values (BRVs) in the form of urinary pesticide metabolites have been proposed for both occupationally exposed workers and children. These BRVs were established using toxicokinetic models developed for each substance, and correspond to safe levels of absorption in humans, regardless of the exposure scenario. The purpose of this chapter is to present a review of a toxicokinetic modeling approach used to determine biological reference values. These are then used to facilitate health risk assessments and decision-making on occupational and environmental pesticide exposures. Such models have the ability to link absorbed dose of the parent compound to exposure biomarkers and critical biological effects. To obtain the safest BRVs for the studied population, simulations of exposure scenarios were performed using a conservative reference dose such as a no-observed-effect level (NOEL). The various examples discussed in this chapter show the importance of knowledge on urine collections (i.e. spot samples and complete 8-h, 12-h or 24-h collections), sampling strategies, metabolism, relative proportions of the different metabolites in urine, absorption fraction, route of exposure and background contribution of prior exposures. They also show that relying on urinary measurements of specific metabolites appears more accurate when applying this approach to the case of occupational exposures. Conversely, relying on semi-specific metabolites (metabolites common to a category of pesticides) appears more accurate for the health risk assessment of environmental exposures given that the precise pesticides to which subjects are exposed are often unknown. In conclusion, the modeling approach to define BRVs for the relevant pesticides may be useful for public health authorities for managing issues related to health risks resulting from environmental and occupational exposures to pesticides.
    09/2012: pages 105-142; , ISBN: 978-0-9835850-9-1
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    ABSTRACT: Impact of prenatal PCB exposure on birth weight was investigated in various children cohorts and findings of published studies show inconsistencies. Because a direct comparison of results obtained from different studies remains difficult, the "biological concentration-birth weight" relationship is not clearly established. The objective of this research was to perform a systematic analysis of published epidemiological data to reassess relationship between prenatal PCB exposure and low birth weight, using toxicokinetic considerations and a novel standardization procedure of biological concentration data across studies. A systematic analysis of 20 epidemiological studies published up to 2011 on this topic was conducted. This was achieved through a standardization of reported exposure data in terms of total PCBs per kg of lipids in maternal plasma. Systematic analysis of the "standardized biological concentration-birth weight" relationship across studies was then conducted through the application of Hill criteria. Combining results of all 20 reviewed studies did not allow to establish an association between prenatal exposure to PCBs at the described levels and abnormal birth weight (<2500g). Our approach provides a framework for the use of published data to establish "PCB biological concentration-response" relationships.
    Regulatory Toxicology and Pharmacology 06/2012; 64(1):161-76. · 2.13 Impact Factor
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    ABSTRACT: Captan and folpet are two fungicides largely used in agriculture, but biomonitoring data are mostly limited to measurements of captan metabolite concentrations in spot urine samples of workers, which complicate interpretation of results in terms of internal dose estimation, daily variations according to tasks performed, and most plausible routes of exposure. This study aimed at performing repeated biological measurements of exposure to captan and folpet in field workers (i) to better assess internal dose along with main routes-of-entry according to tasks and (ii) to establish most appropriate sampling and analysis strategies. The detailed urinary excretion time courses of specific and non-specific biomarkers of exposure to captan and folpet were established in tree farmers (n = 2) and grape growers (n = 3) over a typical workweek (seven consecutive days), including spraying and harvest activities. The impact of the expression of urinary measurements [excretion rate values adjusted or not for creatinine or cumulative amounts over given time periods (8, 12, and 24 h)] was evaluated. Absorbed doses and main routes-of-entry were then estimated from the 24-h cumulative urinary amounts through the use of a kinetic model. The time courses showed that exposure levels were higher during spraying than harvest activities. Model simulations also suggest a limited absorption in the studied workers and an exposure mostly through the dermal route. It further pointed out the advantage of expressing biomarker values in terms of body weight-adjusted amounts in repeated 24-h urine collections as compared to concentrations or excretion rates in spot samples, without the necessity for creatinine corrections.
    Annals of Occupational Hygiene 03/2012; 56(7):815-28. · 2.16 Impact Factor
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    ABSTRACT: A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PA(eq) ), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PA(eq) in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PA(eq) . In the case of a dermal application, mean elimination half-life of PI and PA(eq) was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PA(eq) were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PA(eq) data owing to the lack of blood time course data. Copyright © 2011 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 12/2011; · 2.60 Impact Factor
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    Roberto Heredia-Ortiz, Michèle Bouchard
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    ABSTRACT: Measurement of tetrahydrophthalimide (THPI) in urine has been used for the biomonitoring of exposure to the widely used captan fungicide in workers. To allow a better understanding of the toxicokinetics of captan and its key biomarker of exposure, a human multi-compartment model was built to simulate the transformation of captan into THPI and its subsequent excretion while accounting for other non-monitored metabolites. The mathematical parameters of the model were determined from best-fits to the time courses of THPI in blood and urine of five volunteers administered orally 1mg/kg and dermally 10mg/kg of captan. In the case of oral administration, the mean elimination half-life of THPI from the body (either through faeces, urine or metabolism) was found to be 13.43 h. In the case of dermal application, mean THPI elimination half-life was estimated to be 21.27 h and was governed by the dermal absorption rate. The average final fractions of administered dose recovered in urine as THPI were 3.6% and 0.02%, for oral and dermal administration, respectively. Furthermore, according to the model, after oral exposure, only 8.6% of the THPI formed in the GI reaches the bloodstream. As for the dermal absorption fraction of captan, it was estimated to be 0.09%. Finally, the average blood clearance rate of THPI calculated from the oral and dermal data was 0.18 ± 0.03 ml/h and 0.24 ± 0.6 ml/h while the predicted volume of distribution was 3.5 ± 0.6l and 7.5 ± 1.9l, respectively. Our mathematical model is in complete accordance with both independent measurements of THPI levels in blood (R(2)=0.996 for oral and R(2)=0.908 for dermal) and urine (R(2)=0.979 for oral and R(2)=0.982 for dermal) as well as previous experimental data published in the literature.
    Toxicology Letters 09/2011; 213(1):27-34. · 3.15 Impact Factor

Publication Stats

489 Citations
164.52 Total Impact Points

Institutions

  • 1994–2014
    • Université de Montréal
      • • Department of Environmental and Occupational Health
      • • Faculty of Medicine
      • • Public Health Research Institute
      Montréal, Quebec, Canada
  • 2009
    • Institut National de Santé Publique du Québec (INSPQ)
      Québec, Quebec, Canada
  • 1995–2009
    • Université du Québec à Montréal
      Montréal, Quebec, Canada