This study measured levels of environmental contaminants in urine samples from 249 Israeli adults. It found widespread exposure to bisphenol A and organophosphate pesticides. Higher bisphenol A levels were associated with Jewish ethnicity, active smoking, secondhand smoke exposure, and frequent microwave use. Organophosphate pesticide exposure was predicted by age, income, and high fruit consumption. The results suggest intake of fruits is an important source of organophosphate exposure for Israelis. The study provides baseline data that can track changes in exposure from policy actions like pesticide restrictions.

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