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12.2 Goldsmith

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  • 1. 1 Bisphenol A and Organophosphate Exposure in the Israeli Population: Sources and Risk Factors Judith Spungen, Tamar Berman, Rebecca Goldsmith, Thomas Göen, Lena Novack, Hagai Levine, Yona Amitai, Tami Shohat, Itamar Grotto The 9th International Symposium on Biological Monitoring in Occupational and Environmental Health
  • 2. Israel Human Biomonitoring Study Objectives 2 Measure urinary levels of several environmental contaminants in the Israeli population, compare with other populations Cotinine (environmental tobacco smoke - ETS) Bisphenol A (BPA) Phthalates Organophosphate pesticides (OPs) Polycyclic aromatic hydrocarbons Genistein and daidzein (phytoestrogens) Identify demographic, behavioral, and dietary predictors of exposure to these contaminants
  • 3. Israel Human Biomonitoring Study Methods and Study Population 3 Methods: Participants recruited in February – June 2011 Study Population: Study Population (N=249) N/ % Age Range 250 participants from 5 regions in Israel, ages 20 – 74 20-44 164 65.9% 45-74 85 34.1 % Male 132 53 % Female 117 47 % Jewish 184 73.9 % Arab and other 65 26.1 % Gender Spot urine sample and in depth interview Urine samples analyzed at University of Erlangen – Nuremberg in Germany Ethnicity
  • 4. Israel Human Biomonitoring Study Methods: Questions Related to Potential Exposure Sources- (1) 4 Demographics (age, sex, region, urban/rural residence, ethnicity, income, education) Job characteristics Smoking history Pesticide use in home/garden/pet care products Personal care products use (deodorant, perfume) Weight and height Health and disease status Whether on dialysis/had an infusion in last week
  • 5. Israel Human Biomonitoring Study Methods: Questions Related to Potential Exposure Sources- (2) Food Intake and preparation 5 24-hour dietary recall, including food consumption locations Food frequency questionnaire - modified to enable capture of potential exposure sources Questions related to intake of soy products Polycarbonate water bottle/sports bottle use Microwave use Consumption of smoked and/or grilled foods
  • 6. Israel Human Biomonitoring Study The Food Frequency Questionnaire- the format 6 A. The food 1 2 3 4 5 6 7 Milk 0-1% fat (including in coffee), excluding soy Milk, more than 1% fat (including in coffee), excluding soy Chocolate milk or any other type of milk-drink, Soy drink / soy milk Soft white cheese or cream cheese or cottage cheese, more than 5% fat, excluding soy Soft white cheese or cream cheese or cottage cheese, 5% fat, excluding soy Soy based cheese B. Defined portion 1 cup 1 cup 1 cup 1 cup 1 spoon 1 spoon 1 spoon C. No. of portions per day D. No. of portions per week E. No. of portions per month F. Less than once a month or never
  • 7. Israel Human Biomonitoring Study The 24 hour recall questionnaire; the format 7 The multiple pass method, validated and used in NHANES and other major surveys, was used. Specially trained interviewers, using the Israel Food and Food Quantities Guide, probe for details, including quantities ,of all foods and beverages consumed in the preceding 24 hours. Item Letter 1 Hour 2 Where did Which you meal eat/drink this was it? item? 3 4 Item name Food/drink description 5 6 1 2 3 4 What quantity did you eat/drink? 7
  • 8. Israel Human Biomonitoring Study Methods: Estimating Intakes of Canned Fish, Fruits, Vegetables 8 Food mixtures reported by study respondents were disaggregated to allow estimation of canned fish, fruit, and vegetable intakes from 24-hour recall data. Food labels, data from manufactures, and recipes were used to aid disaggregation. Examples: Food Eggplant with mayonnaise salad Food Pizza with olives Ingredient eggplant other ingredients Ingredient tomatoes olives garlic other ingredients % 70 30 % 31.9 3.9 0.5 63.7
  • 9. Results: Urinary BPA Concentrations Compared with other International Populations 9 Country of Year Median creatinine Age adjusted urinary Study Population concentration (µg/g) Reference US 1.8 20 + 2009-2010 CDC, 2012 Canada 1.5 20-39 2007-2009 Health Canada, 2010 Belgium Korea Germany Israel 2.25 2.09 1.62 2.3 1-75 18 -69 20 -30 20 - 73 2011 2009 2009 2011 Pirard et al 2012 Kim et al 2011 Koch et al 2012
  • 10. Results: Demographic Factors Related to Urinary BPA Concentrations - Ethnicity 10 In a multivariate analysis: urinary concentrations were 2.34 times higher in Jews compared to other ethnicities (p < 0.001) Possible explanations: Differences in consumption of meals outside the home Differences in place of residence – urban/ rural living
  • 11. Results: Behavioral Factors Related to Urinary BPA Concentrations - Active Smoking 11 2.38 1.65 P=0.045
  • 12. Results: Behavioral Factors Related to Urinary BPA Concentrations Exposure to Environmental Tobacco Smoke 12 Urinary BPA concentrations were 1.40 times higher in nonsmoking study participants with urinary cotinine concentrations above 4 μg/L compared to those with urinary cotinine concentrations below 4 μg/L (p=0.06). Possible explanations Inhaled and exhaled tobacco smoke may be a source of BPA because BPA comprises 25% of the weight of some cigarette filters. It is possible that smoking is a surrogate for another behavior correlated with BPA exposure.
  • 13. Results: Dietary Factors Related to Urinary BPA Concentrations - Heating Food in Microwave 13 Individuals who reported using a microwave to heat food at least once a week to several times a day had significantly higher urinary BPA concentrations (GM above 2.11µg/g) compared to those who reported using a microwave to heat food less than once a month or not at all (GM = 1.10, p < 0.01). This effect had borderline significance in the multivariate model, but was not included in the final model because of small sample size. Possible explanation: BPA is used in the manufacture of polycarbonate containers for microwave heating and polysulfone microwave cookware
  • 14. Results: Dietary Factors NOT Significantly Related to Urinary BPA Concentrations 14 Consumption of water in polycarbonate water or sports bottles did not significantly affect urinary BPA concentrations. Only about 20% reported regularly drinking from these sports bottles. Individuals who consumed canned fish had higher urinary BPA concentrations (GM = 2.36 μg/g) compared to those who don’t consume canned fish ( GM= 1.87 μg/g) but the difference was not significant (p=0.478).
  • 15. Results: Urinary Concentrations of Organophosphate Pesticide Metabolites 15 OP metabolites detected in all urine samples Urinary concentrations of DMP, DMTP, and DEP were above the limit of quantification (0.3 µg/L) in over 98% of the samples Urinary concentrations of DETP and DMDTP were above the limit of quantification in ~ 75% of the samples
  • 16. Results: Urinary Organophosphate Metabolite Concentrations Compared with other International Populations 16 Median creatinine adjusted dialkyl phosphate urinary concentrations (ug/g) * Median urinary concentrations of DMP, DEP, and DETP were below the LOD in the US general population (NHANES)
  • 17. Results: Fruit and vegetable intake in study population, by demographic characteristics (1) 17 Females tended to consume more fruit than men – median intakes of 1.70 and 0.90 gm/kg body weight respectively (difference not significant, p= 0.38) Females tended to consume more vegetables than men – median intakes of 3.30 and 2.70 gm/kg body weight respectively (difference not significant, p= 0.16) Jewish participants tended to consume more fruits than Arabs – median intakes of 1.73 and 1.21 gm/kg body weight respectively (difference not significant, p= 0.67) Jewish participants tended to consume more vegetables than Arabs – median intakes of 3.05 and 2.46 gm/kg body weight respectively (difference not significant, p= 0.16)
  • 18. Results: Fruit and vegetable intake in study population, by demographic characteristics (cont.) 18 Higher income participants tended to consume more fruits; median intakes of 2.38 and 1.14 gm/kg body weight respectively, (difference not significant, p= 0.55) Higher income participants tended to consume more vegetables; median intakes of 3.98 and 3.00 gm/kg body weight respectively, (difference not significant, p= 0.77) Higher education participants tended to consume more fruits; median intakes of 2.37 and 0.90 gm/kg body weight respectively, (difference not significant, p= 0.35) Higher education participants tended to consume less vegetables; median intakes of 2.38 and 2.84 gm/kg body weight respectively, (difference not significant, p= 0.57)
  • 19. Possible Explanations for Relatively High Urinary OP Metabolite Levels in Israeli Adults 19 High intake of fruits and vegetables in study population (per kg body weight), relative to general US population Differences in agricultural use of OP pesticides (regulatory status and usage patterns)
  • 20. Results: Demographic and Dietary Predictors of OP Exposure (Univariate Analysis) 20 Total unadjusted dialkyl phosphates significantly associated with high household income (0.231 micromoles/L compared to 0.147, p=0.036) Total dialkyl phosphates higher in individuals with fruit consumption above the 75th percentile (0.263 micromoles/L compared to 0.20, p=0.063)
  • 21. Results: Demographic and Dietary Predictors of OP Exposure (Multivariate Analysis) 21 Factor Effect p-value 1.01 0.040 1 1.40 1.59 --0.104 0.025 1.01 0.020 1 1.45 1.57 --0.096 0.043 1.26 1.27 0.043 0.073 Total molar quantity Age, years Income <NIS 5,000 NIS 5,000-10,000 ≥NIS10,000 Dimethyl total quantity Age, years Income <NIS 5,000 NIS 5,000-10,000 ≥NIS10,000 Diethyl total quantity Females vs. males Consumption of Fruits above 75th percentile
  • 22. Regulatory Status of Selected OP Pesticides (Agricultural Use) in Israel, US, and Europe, 2011* 22 Active Ingredient Israel US Parathion - methyl Registered: pears, apples, nectarines, peaches, others Most food uses banned Banned 2003 1999; final cancellation of use 2012 Azinphos – methyl Registered: tomatoes, pears, citrus, others Most food uses banned Banned 2007 1999; final cancellation of use 2012 Fenthion Registered : peaches, pears, apples, plums, others Banned 2003 Banned 2004 Chlorpyrifos Registered for use on variety of crops including tomatoes, grapes, apples Registered for use on variety of crops Not for use in tomatoes; limited use in apples Registered for use on variety of crops * year urine samples were collected Europe
  • 23. Organophosphate Residues in Fruits and Vegetables in Israel, Sampled 2006 – 2010a 23 Pesticide Chlorpyrifos Malathion Azinphos-methyl Dimethoate Phosmet Methamidophos Pirimphos-methyl Dichlorvos Methidathion Fenthion Diazinon Tolclophos-methyl Fenamiphos Parathion-methyl Cadusafos Oxydemethon-methyl a Number of samples in which pesticide was detected b 288 144 144 116 94 77 36 35 35 26 20 14 5 3 3 1 Number of samples in which pesticide was detected above Maximum Residue Level b 51 32 3 7 7 40 2 20 0 1 11 13 5 2 2 0 Based on data from Israel Ministry of Health, 2012 b Resulting DAP metabolites (primary, secondary, tertiary) DETP, DEP DMDTP, DMTP, DMP DMDTP, DMTP, DMP DMDTP, DMTP, DMP DMDTP, DMTP, DMP None DMTP, DMP DMP DMDTP, DMTP, DMP DMTP, DMP DETP, DEP DMTP, DMP None DMTP, DMP None DMTP, DMP Out of a total of 5558 food samples
  • 24. Ministry of Health Pesticide Residue Data (2006 - 2010) Support Hypothesis that Fruits and Vegetables are Source of OP Exposure 24 OP pesticide % Residues above the Maximum Residue Level (MRL)* Chlorpyrifos 18% Fenamiphos 100 % Malathion 22% Methamidiphos 52% Dimethoate 6% Dichlorvos 57% Diazinon 55% * Number of results exceeding MRL/number of results in which OP was detected
  • 25. Conclusions 25 The general population in Israel is widely exposed to Bisphenol A and Organophosphate pesticides Predictors of BPA exposure include Jewish ethnicity, active smoking, exposure to environmental tobacco smoke, frequent microwave use Intake of fruits (but not vegetables) is an important source of exposure to organophosphate pesticides
  • 26. Strengths and Limitations of the Study 26 Limitations • Convenience non-random sampling technique • Exposure estimates based on a single spot urine sample Strengths • Individuals recruited from different ethnic groups within Israel, with wide geographical distribution. • Very detailed data on dietary habits collected, including consumption of specific fruits and vegetables in the 24 hours prior to the urine sample • Laboratory methods were of high validity and sensitivity
  • 27. Policy changes and Implications 27 Since conducting the study, ten of the 19 OP’s registered in Israel are being phased out, with final cancellation expected in 2014. The data collected can provide baseline information on exposure to OP’s and other contaminants, which can be used to track exposure changes, resulting from policy changes. The study also collected cotinine data, and further monitoring will enable assessment of the impact of antismoking legislation.
  • 28. Plans for Further Biomonitoring in the General Population in Israel 28 Ministry of Health RAV MABAT (Health and Nutrition Survey) in 2014-5, will include collection of urine samples Study sample will include children ages 2 and up We plan to analyze urinary levels of cotinine (biomarker of environmental tobacco smoke) and OP metabolites in urine samples from 300 participants, including children We plan to store urine for future analysis of additional contaminants such as BPA and phthalates
  • 29. THANK YOU 29 Environment and Health Fund for generous support of the study Advisory Committee: Dr. Lital Keinan-Boker, Dr. Shlomo Almog, Dr. Orna Matzner, Prof. Jeremy Kark, Dr. Eric Amster, Dr. John Young
  • 30. Thank you for your attention! 30