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University of California at Berkeley Center for Children's Environmental Health Research
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Principal Investigator: Brenda Eskenazi, PhD
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The activities of the Children’s Center at UC Berkeley are based in the Salinas Valley, California, an agricultural region located southeast of the San Francisco Bay Area. The Salinas Valley is often referred to as the “nation’s salad bowl”, growing primarily lettuce, strawberries, artichokes, broccoli, and grapes. More than half a million pounds of organophosphate (OP) pesticides are used each year in this region.
The goals of the UC Berkeley Children’s Center are:
- To assess pesticide and other environmental exposures in pregnant women and young children
- To examine the potential health effects of these exposures on childhood growth, neurodevelopment and respiratory disease
- To learn more about the mechanisms of pesticide neuro- and immunotoxicity;
- To develop community-based outreach and interventions that reduce take-home pesticide exposure to children of farmworkers.
Primary Exposures: Pesticides
Primary Outcomes: Child neurodevelopment,
growth, and respiratory disease
The goal of this on-going study is to assess the health effects of low-level, chronic pesticide exposure and other exposures in children living in an agricultural community. The study population is comprised of 536 infants, born in 2000-2001, whose mothers were enrolled during pregnancy. Exposure to pesticides and other environmental contaminants was assessed in urine and blood of the mothers during pregnancy and the children at birth, 6 months, 1, 2, 3½, 5 and, currently, 7 years of age. The children have been examined at each of these ages to assess their growth, neurodevelopment, respiratory disease, and general health.
This study has found:
- Pregnant women in the UC-Berkeley study showed higher OP urinary
metabolite levels than women of child-bearing age who participated in
the National Health and Nutrition Examination Survey (NHANES). Levels
in samples collected in the postpartum period were about twice as high
levels during pregnancy. Researchers hypothesize that significant
changes in maternal physiology after giving birth may affect the
internal distribution of pesticides and other toxicants (Bradman et al
2005). - Under new EPA cumulative risk assessment guidelines for OPs, about 15%
of pregnant women participating in the CHAMACOS project may have cumulative
OP pesticide exposures exceeding the health protective reference value (Castorina
et al 2003).
- DDT and DDE levels were significantly higher in pregnant CHAMACOS women
compared to U.S. national reference data. Women who were born in coastal
Mexico, where DDT was used for agriculture and malaria control until the
2000, had much higher levels compared to women born in central Mexico or
the United States (Bradman
et al. 2006).
- Housing quality was very poor in the homes of CHAMACOS participants. We
found a high prevalence of cockroach and rodent infestations, mold, peeling
paint, water damage, etc. Homes with housing disrepair indicators had
higher rates of pest infestations. Compared to a national survey by
HUD, CHAMACOS participants were more likely to have rodents, peeling paint,
leaks under sinks, and much higher residential densities. Pesticides
were stored or used in about 50% of households (Bradman
et al 2005).
- Higher levels of organophosphate (OP) pesticide metabolites in maternal urine during pregnancy were associated with shorter gestational duration. A ten-fold increase in average dimethyl, but not diethyl, phosphate metabolites was associated with a decrease of three days in gestational duration (p=0.02). Lower levels of acetyl cholinesterase (suggesting higher OP exposure) in umbilical cord blood were also associated with significantly shorter length of gestation. No adverse associations were found between OP exposure and infant birth weight, length or head circumference (Eskenazi et al 2004).
- Researchers found that hexachlorobenzene was associated with decreased
length of gestation. No effect was seen on birth weight or length. No
significant associations were found with any other organochlorine analyzed,
including DDT and DDE. (Fenster
et al, 2006)
- Neonates whose mothers had higher OP pesticide metabolite levels during
pregnancy were more likely to have abnormal reflexes in the neonatal period
as assessed by the Brazelton Neonatal Behavioral Assessment Scale (BNBAS).
OP exposure was associated with both an increase in number of abnormal reflexes
and the proportion of infants with more than three abnormal reflexes. No
detrimental associations were found with the other BNBAS clusters (Young
et al. 2005).
- Higher levels of OP pesticide metabolites during pregnancy were also
associated with poorer mental development index at age 24 months.
Although prenatal exposure was negatively associated with mental
development, postnatal exposure appeared to be positively
associated. Higher OP metabolite levels in both the prenatal and
postnatal periods were associated with increased risk of pervasive
developmental disorder (Eskenazi et al. 2007)
- UC Berkeley Center researchers also found a negative association
between maternal DDT levels during pregnancy and child mental
development at 24 months. Each ten-fold increase in DDT level was
associated with a 2- to 3-point decrease in mental development,
corresponding to a 7- to 10-point decrease across the range of
exposure of the population (Eskenazi et al 2006).
Progress Reports
Original funding period (1998-2003)
The Epidemiological Investigation of the Effects of Pesticide Exposure on Neurodevelopmental, Growth, and Respiratory Health of Farmworker Children
Current funding period (2003-2008)
Community-Based Participatory Research Project: CHAMACOS
The Center has implemented two community-based participatory intervention research studies. The goal of these intervention studies is develop sustainable methods for reducing pesticide exposures to farmworkers and their children. In particular, we are interested in reducing “take home” exposures (i.e. pesticides on the parents clothing, shoes, and skin that are transported from the fields into the home). Our community partners and farmworker leaders played a key role in developing these interventions.
Field-based Technical Intervention: Working with strawberry growers in the Salinas Valley, we developed a technical intervention that was implemented with farmworkers in the fields. This intervention was a randomized control trial and included both an intervention group and a control group.
The intervention group received:
- Warm water: Because of cultural beliefs that cold water on warm hands can cause arthritis, we developed a method of providing warm water to the sinks in the fields, using a central hot water heater and insulated water tanks.
- Coveralls: To reduce take-home exposure on clothing, we worked with farmworkers to design a light-weight coverall that could be worn over clothes. Workers were provided with 5 coveralls. Coveralls were removed upon leaving the fields and picked up by a laundry service.
- Gloves: Disposable gloves were provided at work to prevent pesticides on hands.
- Education sessions: Workers received 5 brief educational sessions in the fields. These sessions focused on educating workers about the proper implementation of protective behaviors such as hand washing and troubleshooting barriers workers were experiencing in adopting these behaviors. We also instructed workers about other ways to reduce pesticide exposure to themselves and their families.
The control group received a comparable intervention after all final data collection activities ended. They received education sessions, coveralls, and gloves. Our grower collaborators were permitted to keep the water heater at the end of the study.
This study found:
- Wearing coveralls likely reduced pesticide residues on regular work clothing (Bradman et al. in preparation)
- Leaving coveralls at work reduced the potential for take-home pesticide exposure (Bradman et al. in preparation)
- Workers who wore gloves had significantly lower amounts of pesticides on their hands and in their urine (Bradman et al. in preparation)
- Worker who ate strawberries directly from the fields had higher levels of pesticides in their urine than those who did not (Bradman et al. in preparation)
-
Workers were very positive about the coveralls and gloves. They felt they did not hamper productivity. Approximately 85% of workers said they would always wear coveralls and gloves if employers provided them (Salvatore et al., in preparation)
- Workers appreciated warm water, but the distance to the sinks, the number of workers using each sink, and the piece-rate pay structure were barriers to handwashing (Salvatore et al., in preparation)
(Bradman, A. et al. in preparation; Salvatore, A. et al., in preparation)
Home-based Educational intervention: The home-based intervention with farmworker households consisted of three visits over three months by a team of trained bilingual Environmental Health Promoters (EHPs) from the community. During the home visits EHPs provided educational sessions to participants and other household members. This intervention was a randomized control trial and included both an intervention group and a control group.
The intervention group received:
- Home-based Educational Sessions: These educational sessions focused on explaining the risks of pesticide exposures to adults and children, assessing sources of “take home” and at-home pesticide exposures, and offering advice about pesticide exposure prevention steps
- Assistance in Developing a Household Action Plan to reduce pesticide exposures: EHPs assisted each household in developing an action plan to reduce the amount of pesticide exposure to their families and household members. Elements of household action plans differed among households. EHPs also worked with participants to troubleshoot problems encountered in carrying-out household action plans.
The control group received a comparable educational intervention after all final data collection activities ended.
Results of this study are still being analyzed.
Progress Reports
Original funding period (1998-2003)
Community Based Intervention to Reduce Pesticide Exposures to Young Children
The goals of these studies are to identify child-specific pathways of pesticide exposure and to validate methods of exposure measurement in pregnant women and children.
Specific exposure studies conducted by the Children’s Center at UC Berkeley are as follows:
Quantitative Exposure Analysis (QEA) Study: Conducted in 2002, the goal of the QEA was to quantify the relative contributions of diet and ambient household exposures to infant and toddler pesticide loads. Twenty children participated in this intensive study, ten between 5 and 11 months of age and ten between 21 and 27 months of age. Data collection included an exposure questionnaire for parents, a home inspection form, 24-hour food diaries, and 24-hour child time-activity logs. Pesticide levels were measured in indoor and outdoor air samples, in indoor dust, and on floors in the household. To explore the contribution of children’s crawling, walking, and hand-to-mouth activities to exposure levels, pesticide levels were also measured on union suits and socks worn by the child and on teething objects or toys. Children’s pesticide load was measured through pesticide metabolite levels in urine.
Key findings from this study:
- Toddlers accumulate more pesticides on their clothing than younger infants (Bradman, Whitaker et al. 2006).
- Toddlers also have higher urinary metabolite levels than younger infants (Bradman, Whitaker et al. 2006).
- Different ambient pesticide measures were not inter-correlated, suggesting that single measures are insufficient to classify a household’s pesticide levels (Bradman, Whitaker et al. 2006).
- Amongst ambient samples, house dust and floor wipes contained the highest number of pesticides and levels (Bradman, Whitaker et al. 2006).
Child Validation Study (CVS): Conducted in 2004, the purpose of the CVS was to validate the use of urinary dialkylphosphate (DAP) metabolite measures from one-void-only urine sampling (“spot sampling”) as an appropriate proxy for measures in 24-hour urine samples, considered the gold standard measurement. Twenty-five 3- to 5-year-old children participated in a 7-day sampling regimen, which included daily spot-sampling, two 24-hr samples, and two first morning voids. Parents completed an initial exposure questionnaire and home walkthrough, as well as a brief daily diet and exposure questionnaire.
Initial findings from this study:
- DAP metabolite levels in spot samples are moderately correlated with those in same-day 24-hour samples.
- However, levels in 24-hour samples collected three days apart were not correlated with one another.
Organic Diet Trial: Twenty families in the agricultural Salinas Valley, CA and twenty families in urban Oakland, CA were provided with organic food for 7 days. Metabolites of OP pesticides were measured in the urine of the preschool aged children every day during the conventional food and organic food portions of the trial. This study will help determine the relative contribution of diet to pesticide levels in young children and will compare similar populations living in urban and agricultural areas.
Peripartum Study: This study will enroll women during pregnancy and measure their urinary and blood pesticide levels before and after delivery, to learn more about the pharmacokinetics of OP pesticide metabolism in pregnant mothers.
Progress Reports
Original funding period (1998-2003)
A Comprehensive Assessment of Sources of Pesticide Contamination, Concentrations in Pathways, and Exposure-prone Behavior
Current funding period (2003-2008)
Pesticide Exposure Assessment Project
4. Mechanism Studies
These lab-based studies take advantage of the large repository of biological samples from the CHAMACOS cohort of pregnant women and children to explore the mechanisms of pesticide immuno- and neurotoxicity and to elucidate differences in susceptibility to pesticides through gene-environment interaction.
Immunotoxicity: Researchers are using in vitro cultures of human cells to examine the effects of individual and combined exposures to pesticides, endotoxin and allergens on cytokine response. We are also examining levels of intracellular Th1 and Th2-type cytokines in whole blood collected from members of the CHAMACOS cohort at 1, 2, and 5 years of age to examine the effects of these exposures in vivo.
Key findings:
- Immunological assessment was enhanced by high through-put analysis of 10 different cytokines (by Luminex and ELISA) after combined treatment of blood cultures with a combination of OP pesticides and metabolites with endotoxin and dust mite allergen. For the first time potentiation of cytokine response was demonstrated at low doses of CPO in combination with endotoxin. (Duramad, Tager et al 2006).
- Analysis of cytokine profiles in 12 and 24 month children from CHAMACOS cohort demonstrated increased variability in older children. Th1 was associated with parents work in agriculture, breastfeeding and pets at home (Duramad, Harley et al, 2006)
Neurotoxicity: Researchers are examining the role of neurotoxic target esterase (NTE) activity in neurotoxicity in a neuroblastoma cell line and in human lymphocytes using a new method based on interaction with a cellular target (lysophospholipids).
Key results:
- A new radioactive NTE-lysoPLA assay was developed and validated against the colorimetric lysolecithin NTE assay. The new assay has improved sensitivity and is suitable for use with small volumes of biological samples.
- Two new enzymatic activities sensitive to inhibition by organophosphate pesticides independent of cholinesterase were found in red blood cells of CHAMACOS pregnant women and newborns. Characterization in respect to neurotoxicity is in progress (two papers are in preparation).
PON1 as a Predictor of Pesticide Susceptibility: Given the same level of pesticide exposure, some individuals may be more susceptible to the potential adverse effects of pesticides depending on their genetic makeup and expression of genes encoding key metabolic enzymes. For example, the human enzyme paraoxonase (PON1) detoxifies various organophosphate pesticides with different efficiency depending on the main single nucleotide polymorphism (SNP) at position 192 and other SNPs along promoter and coding regions.
The pesticide susceptibility project is determining PON1 genotype for two polymorphisms (192 and –108) and measuring enzyme activity levels (paraoxonase, diazoxonase, chlorpyrifos oxonase, and arylesterase) in maternal and child blood from the CHAMACOS cohort. We will also examine whether PON1 status modifies the association of pesticides and neurodevelopment.
Key results:
- PON1 activity is very low in newborns, with the lowest levels in children with vulnerable genotypes. (Furlong et al, 2006; Holland et al, 2006)
- Based on their PON1 status, some newborns may be 26 to 50 times more susceptible to exposure to certain organophosphate pesticides than other newborns. (Furlong et al, 2006; Holland et al, 2006)
- The most susceptible newborns may be 65 to 130 times more sensitive to organophosphate pesticides than the least susceptible some adults. (Furlong et al, 2006; Holland et al, 2006)
Progress Reports
Current funding period (2003-2008)
Mechanisms of Pesticide Neuro and Immunotoxicity in Children Project
5. Community Outreach Activities
In addition to research activities, CHAMACOS also works with farmworker groups, health outreach programs, schools, and other community agencies to provide education about preventing pesticide and other environmental exposures to children.
Educational materials have been developed in English and Spanish for low literacy populations and include environmental topics such as integrated pest management, pesticide safety, and air pollution, as well as general health topics, including accident prevention, safety checklists for children, second hand smoke, and sun exposure.
Community Outreach and Translation Core
Clinica de Salud del Valle de Salinas (CSVS) 
Natividad Medical Center
South County Outreach Effort (SCORE)
Monterey County Health Department
California Rural Legal Assistance Program (CRLA)
Grower-Shipper Association of Central California
Bradman A,
Chevrier J, Tager I, Lipsett M, Sedgwick J, Macher J, Vargas AB, Cabrera
EB, Camacho JM, Weldon R, Kogut K, Jewell NP, Eskenazi B 2005. Association
of housing disrepair indicators with cockroach and rodent infestations in
a cohort of pregnant Latina women and their children. Environ Health
Perspect. 2005 Dec;113(12):1795-801.
Bradman A,
Fenster L, Sjodin A, Jones RS, Pattersonn DG, Eskenazi B 2007. Polybrominated
Diphenyl Ether Levels in the Blood of Pregnant Women Living in an Agricultural
Community in California. Environ Health Perspect. 2007 Jan;115(1):71–74.
Bradman A, Eskenazi
B, Barr DB, Bravo R, Castorina R, Chevrier J, Kogut K, Harnly ME, McKone TE
2005. Organophosphate urinary metabolite levels during pregnancy
and after delivery in women living in an agricultural community. Environ
Health Perspect. 2005 Dec; 113(12):1802-7.
Bradman
A, Schwartz JM, Fenster L, Barr D, Holland NT, Eskenazi B. 2006. Factors
predicting organochlorine pesticide levels in pregnant women living in the
Salinas Valley, California. JESEE. In
press, 2006.
Bradman
A, Whitaker D, Quirós L, Castorina R, Henn BC, Nishioka M, Morgan J, Barr
DB, Harnly M, Brisbin JA, Kauffman PE, Sheldon LS, McKone TE, Eskenazi B. Pesticides and their Metabolites in the Homes and Urine of Farmworker Children
Living in the Salinas Valley, CA. JESEE. In press, 2006.
Castorina
R, Bradman A, McKone TE, Barr DB, Harnly ME, Eskenazi B 2003. Cumulative
Organophosphate Pesticide Exposure and Risk Assessment among Pregnant Women
Living in an Agricultural Community: A Case Study from the CHAMACOS Cohort. Environ
Health Perspect. 2003 Oct; 111(13):1640-8.
Duramad
P, Tager IB, Leikauf J, Eskenazi B, Holland NT 2006. Expression
of Th1/Th2 cytokines in human blood after in vitro treatment with chlorpyrifos,
and its metabolites, in combination with endotoxin LPS and allergen Der p1. J
Appl Toxicol. 2006 Sep-Oct;26(5):458-65.
Duramad
P, Harley K, Lipsett M, Bradman A, Eskenazi B, Holland NT, Tager IB 2006.
Early environmental exposures and intracellular th1/Th2 cytokine profiles
in 24-month old children living in an agricultural area. Environ Health Perspect.
2006 Dec; 114(12):1916-22.
Eskenazi
B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland
NT 2004. Association of in utero organophosphate pesticide exposure
and fetal growth and length of gestation in an agricultural population. Environ
Health Perspect. 2004 Jul;112(10):1116-24.
Eskenazi
B, Marks AR, Bradman A, Fenster L, Johnson C, Barr DB, Jewell NP 2006.
In utero exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene
(DDE) and neurodevelopment among young Mexican American children. Pediatrics.
2006 Jul;118:233-241.
Eskenazi
B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP 2007.
Organophosphate Pesticide Exposure and Neurodevelopment in Young
Mexican-American Children. Environ Health Perspect. 2007 May;115(5),
792-798.
Fenster L,
Eskenazi B, Anderson M, Bradman A, Harley K, Hernandez H, Hubbard A, Barr
DB 2006. Association of in utero organochlorine pesticide exposure
and fetal growth and length of gestation in an agricultural population. Environ
Health Perspect. 2006 Apr;114(4):597-602.
Furlong
CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B 2006. PON1 status
of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenet
Genomics. 2006;16:183-190.
Holland N,
Furlong C, Bastaki M, Richter R, Bradman A, Huen K, Beckman K, Eskenazi B
2006. Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino
mothers and newborns. Environ Health Perspect. 2006 Jul;114(7):985-91.
Young
JG, Eskenazi B, Gladstone EA, Bradman A, Pedersen L, Johnson C, Barr DB,
Furlong CE, Holland NT 2005. Association between in utero organophosphate
pesticide exposure and abnormal reflexes in neonates. Neurotoxicology.
2005 Mar;26(2):199-209.
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