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

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Israel Human Biomonitoring StudyObjectives

Measure urinary levels of several environmental contaminants in the Israeli population, compare with other populations

Cotinine (environmental tobacco smoke - ETS)Bisphenol A (BPA) PhthalatesOrganophosphate pesticides (OPs)Polycyclic aromatic hydrocarbonsGenistein and daidzein (phytoestrogens)

Identify demographic, behavioral, and dietary predictors of exposure to these contaminants

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Israel Human Biomonitoring StudyMethods and Study Population

Methods: Participants recruited in February – June 2011

250 participants from 5 regions in Israel, ages 20 – 74

Spot urine sample and in depth interview

Urine samples analyzed at University of Erlangen –Nuremberg in Germany

Study Population: Study Population (N=249)N/ %

Age Range

20-44 164 65.9%

45-74 85 34.1 %

Gender

Male 132 53 %

Female 117 47 %

Ethnicity

Jewish 184 73.9 %

Arab and other 65 26.1 %

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Israel Human Biomonitoring StudyMethods: Questions Related to Potential Exposure Sources- (1)

Demographics (age, sex, region, urban/rural residence, ethnicity, income, education)Job characteristicsSmoking historyPesticide 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

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Israel Human Biomonitoring StudyMethods: Questions Related to Potential Exposure Sources- (2) Food Intake and preparation

24-hour dietary recall, including food consumption locationsFood frequency questionnaire - modified to enable capture of potential exposure sourcesQuestions related to intake of soy productsPolycarbonate water bottle/sports bottle useMicrowave useConsumption of smoked and/or grilled foods

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Israel Human Biomonitoring StudyThe Food Frequency Questionnaire- the format

A. The food B. Defined portion

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

1 Milk 0-1% fat (including in coffee), excluding soy

1 cup

2 Milk, more than 1% fat (including in coffee), excluding soy

1 cup

3 Chocolate milk or any other type of milk-drink,

1 cup

4 Soy drink / soy milk 1 cup5 Soft white cheese or cream

cheese or cottage cheese, more than 5% fat, excluding soy

1 spoon

6 Soft white cheese or cream cheese or cottage cheese, 5% fat, excluding soy

1 spoon

7 Soy based cheese 1 spoon

Israel Human Biomonitoring StudyThe 24 hour recall questionnaire; the format

Item Letter

Hour Where did you eat/drink this item?

Which meal was it?

Item name

Food/drink description What quantity did you eat/drink?

1 2 3 4 5 6 7

1

2

3

4

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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.

Israel Human Biomonitoring StudyMethods: Estimating Intakes of Canned Fish, Fruits, Vegetables

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 Ingredient %

Eggplant with mayonnaise saladeggplant 70other ingredients 30

Food Ingredient %

Pizza with olives

tomatoes 31.9olives 3.9garlic 0.5other ingredients 63.7

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Results: Urinary BPA Concentrations Compared with other International Populations

Country Median creatinineadjusted urinaryconcentration(µg/g)

Age ofStudyPopulation

Year Reference

US 1.8 20 + 2009-2010 CDC, 2012

Canada 1.5 20-39 2007-2009 Health Canada, 2010

Belgium 2.25 1-75 2011 Pirard et al 2012 Korea 2.09 18 -69 2009 Kim et al 2011Germany 1.62 20 -30 2009 Koch et al 2012Israel 2.3 20 - 73 2011

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Results: Demographic Factors Related to Urinary BPA Concentrations - Ethnicity

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 homeDifferences in place of residence – urban/ rural living

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Results:Behavioral Factors Related to Urinary BPA Concentrations - Active Smoking

P=0.045

1.65

2.38

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Results: Behavioral Factors Related to Urinary BPA Concentrations -Exposure to Environmental Tobacco Smoke

Urinary BPA concentrations were 1.40 times higher in non-smoking 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.

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Results: Dietary Factors Related to Urinary BPA Concentrations - Heating Food in Microwave

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

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Consumption of water in polycarbonate water orsports bottles did not significantly affect urinaryBPA concentrations. Only about 20% reportedregularly drinking from these sports bottles.

Individuals who consumed canned fish had higherurinary 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 notsignificant (p=0.478).

Results:Dietary Factors NOT Significantly Related to Urinary BPA Concentrations

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Results: Urinary Concentrations of Organophosphate Pesticide Metabolites

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

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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)

Results: Urinary Organophosphate Metabolite Concentrations Compared with other International Populations

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Results: Fruit and vegetable intake in study population, by demographic characteristics (1)

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)

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Results: Fruit and vegetable intake in study population, by demographic characteristics (cont.)

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 lessvegetables; median intakes of 2.38 and 2.84 gm/kg body weight respectively, (difference not significant, p= 0.57)

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Possible Explanations for Relatively High Urinary OP Metabolite Levels in Israeli Adults

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)

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Results: Demographic and Dietary Predictors of OP Exposure (Univariate Analysis)

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)

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Results: Demographic and Dietary Predictors of OP Exposure (Multivariate Analysis)

Factor Effect p-value

Total molar quantityAge, yearsIncome

<NIS 5,000NIS 5,000-10,000≥NIS10,000

1.01

11.401.59

0.040

---0.1040.025

Dimethyl total quantityAge, yearsIncome

<NIS 5,000NIS 5,000-10,000≥NIS10,000

1.01

11.451.57

0.020

---0.0960.043

Diethyl total quantityFemales vs. malesConsumption of Fruits above 75th percentile

1.261.27

0.0430.073

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Regulatory Status of Selected OP Pesticides (Agricultural Use) in Israel, US, and Europe, 2011*

Active Ingredient Israel US Europe

Parathion - methyl Registered: pears, apples, nectarines, peaches, others

Most food uses banned 1999; final cancellation of use 2012

Banned 2003

Azinphos – methyl Registered: tomatoes, pears, citrus, others

Most food uses banned 1999; final cancellation of use 2012

Banned 2007

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

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Organophosphate Residues in Fruits and Vegetables in Israel, Sampled 2006 – 2010a

Pesticide Number of samples in which pesticide was detected b

Number of samples in which pesticide was detected above Maximum Residue Level b

Resulting DAP metabolites (primary, secondary, tertiary)

Chlorpyrifos 288 51 DETP, DEPMalathion 144 32 DMDTP, DMTP, DMPAzinphos-methyl 144 3 DMDTP, DMTP, DMP Dimethoate 116 7 DMDTP, DMTP, DMP Phosmet 94 7 DMDTP, DMTP, DMP Methamidophos 77 40 NonePirimphos-methyl 36 2 DMTP, DMPDichlorvos 35 20 DMPMethidathion 35 0 DMDTP, DMTP, DMP Fenthion 26 1 DMTP, DMP Diazinon 20 11 DETP, DEP Tolclophos-methyl 14 13 DMTP, DMPFenamiphos 5 5 NoneParathion-methyl 3 2 DMTP, DMP Cadusafos 3 2 NoneOxydemethon-methyl 1 0 DMTP, DMP

a Based on data from Israel Ministry of Health, 2012 b Out of a total of 5558 food samples

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Ministry of Health Pesticide Residue Data (2006 - 2010) Support Hypothesis that Fruits and Vegetables are Source of OP Exposure

% Residues above the Maximum Residue Level (MRL)*

OP pesticide

18%Chlorpyrifos

100 %Fenamiphos

22%Malathion

52%Methamidiphos

6%Dimethoate

57%Dichlorvos

55% Diazinon

* Number of results exceeding MRL/number of results in which OP was detected

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Conclusions

The general population in Israel is widely exposed to BisphenolA 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

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Strengths and Limitations of the Study

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

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Policy changes and Implications

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 anti-smoking legislation.

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Plans for Further Biomonitoring in the General Population in Israel

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

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THANK YOU

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

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Thank you for your attention!