Children’s Vulnerability to
Pesticides
Photo: H Murphy – Alahanpanjang, West Sumatra Indonesia, 1996
Why?




Behavioral factors
Biological factors
Bigger doses
Long term effects @ low level exposure
Sources – Child/OP Encounters
Residentia l
use
Parental take-home
Dietary
Drinking
water
Farm proximity
> ¼ mi
Proximity to Farmland Data
from Washington State
PNASH Center Research
Lu C, Fenske RA, Simcox NJ, Kalman D. Pesticide exposure of children in an agricultural community: evidence
of household proximity to farmland and take home exposure pathways. Environ Res. 2000 Nov;84(3):290-302.
Child Behavior Question
CDC reports from a nationally
representative sample of the U.S.
population shows that children have
twice the amount of pesticide byproducts in their urine as adults.
How would you describe to a parent
the behaviors in young children that
would explain this?
Behaviors

Hand to mouth: Taste their

Near the ground: Spend more time on

environment
the ground
Outdoors: Spend more time outside
Agricultural
Workplace/Playground
Geometric Means (µmol/L) and 95% C.I. for OP
Metabolite Concentrations by Sampling Month
(Arrows indicate months of OP pesticides spraying)
Dimethyl DAP concentration (µmol/L)
0.25
0.2
0.15
0.1
0.05
Sampling month
Koch D, Lu C, Fisker-Andersen J, Jolley L, Fenske RA. Temporal association of children's pesticide exposure and
agricultural spraying: report of a longitudinal biological monitoring study. Environ Health Perspect. 2002
Aug;110(8):829-33.
Jul-95
Jun-95
May-95
Apr-95
Mar-95
Feb-95
Jan-95
Dec-94
Nov-94
Oct-94
Sep-94
Aug-94
Jul-94
Jun-94
May-94
Apr-94
Mar-94
Feb-94
Jan-94
Dec-93
Nov-93
0
Behavior:
soil ingestion
2.5 year old
Adult
Indoor
50
20
Outdoor
60
0.4
Soil ingestion
(mg/day)
G. Selevan. EHP 2000;108 Suppl 3:451-455
Child Biology Question
Maria’s husband is an applicator but his blood test
(cholinesterase monitoring program) is normal.
She likes to take her baby with her when she
picks him up from work but was advised against
this. She cannot understand why being around
pesticides would be a problem for her baby when
her husband who had direct contact is fine.
How would you explain to a parent the
biological factors would make a child
more vulnerable than an adult?
Biology- Higher Dose By:
1.
Higher Metabolic Rates
•
Inhales more per day (1.7x) than adult
•
Drinks 2 x more water per their weight than
an adult
Eats 12x more apples per their weight than an
adult
2. Dietary consumption/body weight
•
3. Skin
•
•
More permeable: highest at birth
2.7 x more skin surface/weight than adults
4. Developing organs
Biology: inhalation dose
Inhalation
Age (years) Weight (kg) Rate
(m3/day)
<1
7.6
4.5
“dose”
(m3 per kg
per day)
0.592
1-2
13
6.8
0.523
3-5
18
8.3
0.461
6-8
26
10
0.385
9-11
36
14
0.389
12-14
50
15
0.300
15-17
66
17
0.258
1.7x
Biology: dermal & dietary dose
Newborn
Young Child
Older Child
Adult
0.067
0.047
0.033
0.025
< 1 year
1-10 years
11-19 years
20-64 years
43.5
35.5
18.2
19.9
< 1 year
3-5 years
12-19 years
40-69 years
Citrus
1.9
2.6
1.1
0.9
Apples
5.0
3.8
0.4
0.4
Surface area:
body mass
ratio (m2/kg)
Drinking water
(tap) mean
intake
(ml/kg/day)
2.7 x
2x
Fruit
consumption
(g/kg/day)
12x
G. Selevan. EHP 2000;108 Suppl 3:451-455
Biology: skin permeability

Skin permeability
Highest at birth
Adult permeability by ~ 1 yr.
Vulnerability to Health Effects:
Organs Still Developing

Neurological

Reproductive

Pulmonary

Renal
Skeletal
 Metabolism

Immune
 GI tract

“A little kid goes from a single cell to a laughing, sociable,
intelligent, friendly human being over the course of two years.
That’s dramatic growth and development!”
Kenneth Olden, PhD, former Director, National Institute of Environmental Health Sciences
Metabolic Vulnerability:
e.g. Paraoxonase
Paraoxonase (PON1) is an enzyme that acts
as a detoxifying system for
organophosphate pesticide metabolites
Activity of the enzyme is reduced in
pregnancy, infancy, childhood
Some evidence that PON1 activity can modify
risk of adverse health outcomes in children
birth outcomes (head circumference)
pediatric brain tumors
Nielsen SS. Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides:
The Potential Role of Paraoxonase (PON1) . EHP 2005;113:909-913
Berkowitz GS. In Utero Pesticide Exposure, Maternal Paraoxonase Activity, and Head Circumference. EHP
2004;112:388-391.
Parent Activities Question
Ramon and Rosa’s 3 year old has small amounts
of OP’s in his urine (he was recruited for a
PNASH study). They are asking you how this
could occur. The family live 5 miles from the
closest orchard.
Why is this? What things are the parents doing
that would account for this? What questions will
you ask and what things will you look for in the
household
Dependency

Children rely on adults to provide safe
environments – indoor and out
Sources – Child/OP Encounters
Residentia l
use
Parental take-home
Dietary
Drinking
water
Farm proximity
> ¼ mi
Parental Take-Home
Washington State data from PNASH:
metabolites of OPs in children’s urine
Community Low/Hi Spray
Season
Applicator
Farmworker
Seattle
Fenske RA, Lu C, Curl CL, Shirai JH, Kissel JC. Biologic monitoring to characterize organophosphorus pesticide exposure
among children and workers: an analysis of recent studies in Washington State. Environ Health Perspect. 2005
Nov;113(11):1651-7.
Parent Activity Questions











Source of food and water
Parent occupation?
Shower after working before holding children?
Work clothes and shoes in the house?
Laundry practices ?
Use household pesticides ?
Garden pesticides ?
House and car cleaning ?
Pesticide storage?
Location of day care?
House near fields?
Chlorpyrifos Metabolite Concentrations in the Urine of 22 Children
Before, During, and After Organic Diet Intervention
TCPY daily concentration (µg/L)
25
20
15
10
5
0
-5
N=
Organic
diet
Conventional
diet
Conventional
diet
20
23
23
21
23
23
23
23
22
23
23
23
23
23
21
21
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Sequential day
Lu C, Toepel K, Irish R, Fenske RA, Barr DB, Bravo R. Organic diets significantly lower children's dietary
exposure to organophosphorus pesticides. Environ Health Perspect. 2006 Feb;114(2):260-3.
Impacts on Children
Studies on low level OP exposures among children

The younger the child the greater
consequences of OP exposure on development




Fetus
Soon after birth
Nerve cells affected
Levels so low that they do not affect the
cholinesterase but still damage developing
nerve cells.
What is the Evidence?
Three Studies of Mother-Baby Pairs
Mary Wolff, Stephanie Engel, Gertrud Berkowitz
Mount Sinai School of Medicine
Virginia Rauh, Robin Wyatt, Frederica Perera
Columbia University
Brenda Eskenazi, Kim Harley, Asa Bradman, Amy Marks
University of California, Berkeley
New York Studies
Following 700
mother/baby pairs
for 7 years.



Mother’s air intake
for pesticides
Mother’s blood
Umbilical cord blood
of baby
Followed 409
mother/baby pairs for
3 years.



Mother’s urine
Birth outcomes
Development to age 2
California Studies
600 pregnant Latina women from
working families living in Salinas, a heavy
agriculture area.


OP by-products in urine during pregnancy
and after delivery
Birth outcomes
Biomarkers of Prenatal OP
Pesticide Exposures
In Urine
OP by products
(Dialkyl Phosphates)
Berkeley
X
Mt. Sinai
X
In Blood
Chlorpyrifos
Columbia
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
X
Early Childhood
Neurodevelopmental
Outcome Measurements
Neonatal
Berkeley
X
Mt. Sinai
X
Columbia
Pre-school
Intelligence**
Infant
Development*
Behavioral
Assessment
6M 1Y
X
2Y
X
X
X
X
X
X
* Baley: Tests motor, cognitive, language development
**Wechsler Preschool and Primary Scale of Intelligence (WPPSI)
3Y
3.5Y
5Y
X
X ****
X
*** Brazelton
**** Verbal IQ assessed with PPVT
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
X
Early Childhood
Behavioral Outcome Measurements
Child Behavior
Checklist
2Y
Berkeley
3Y
X
3.5Y
X
Mt. Sinai
Columbia
X
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
AGRICULTURAL
CALIFORNIA
URBAN NEW YORK
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
Characteristics of
Study Populations
Berkeley
(%)
Mt. Sinai
(%)
Columbia
(%)
1
-97
2
20
27
Mex, PR 51
1
-35
65
--
Married
82
29
29
< High school
81
32
35
Race/Ethnicity
Non-Hispanic White
African-American
Hispanic
Other
Mexican
Dominican
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
In summary…

Three scientifically-rigorous, cohort studies




Different populations
Different exposure levels and sources
Exposure measured using biomarkers in urine
(metabolites) and blood (parent compound)
Despite these differences, some patterns
emerge…
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research
Prenatal OP exposure associated
with ……..
 Increased
odds of abnormal reflexes in
neonates
 Poorer mental development in 2 and 3 year
olds
 Poorer verbal IQ in 3½ and 5 year olds
 Increased odds of pervasive developmental
disorder
Source: Kim Harley, PhD UC Berkeley Center for Children’s Environmental Health Research