2013 Progress Report: Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children

EPA Grant Number: R834513C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834513
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for the Health Assessment of Mothers and Children of Salinas - UC Berkeley School of Public Health: CHAMACOS Office, Berkeley, CA
Center Director: Eskenazi, Brenda
Title: Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
Investigators: Eskenazi, Brenda , Arora, Manish , Bradman, Asa , Eisen, Ellen , Harley, Kim , Holland, Nina T. , Jerrett, Michael , Molitor, John , Sjodin, Andreas , Smith, Donald
Current Investigators: Eskenazi, Brenda , Arora, Manish , Bradman, Asa , Harley, Kim , Holland, Nina T. , Jerrett, Michael , Molitor, John , Sjodin, Andreas , Smith, Donald
Institution: University of California - Berkeley
Current Institution: University of California - Berkeley , Centers for Disease Control and Prevention , Mount Sinai School of Medicine , Oregon State University , University of California - Santa Cruz
EPA Project Officer: Louie, Nica
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2016)
Project Period Covered by this Report: June 1, 2012 through May 31,2013
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text |  Recipients Lists
Research Category: Children's Health , Health

Objective:

In Project B (R834513C002) we will study novel methods of examining prenatal exposure to Mn, PBDE, and DDT/E compounds using shed deciduous teeth and GIS methods. The specific aims are:

Specific Aim 1: To measure Mn, PBDEs, and DDT/E in shed deciduous teeth.

Specific Aim 2: To determine the relationship between Mn, PBDE, and DDT/E levels in teeth with other relevant biological measures.

Specific Aim 3: To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth, hair and child blood.

Specific Aim 4: To identify population correlates of PBDEs and DDT/E exposure in 9- year-old boys.

Progress Summary:

Specific Aim 1: To measure Mn, PBDEs, and DDT/E in shed deciduous teeth. (Population: CHAMACOS children participating since birth.) Manganese: We have successfully developed a method for measuring Mn in human teeth by laser ablation ICP-mass spectrometry (LA/ICP/MS), including analysis of 307 teeth collected from the CHAMACOS cohort. Rather than calculate one estimate of cumulative exposure over the entire prenatal period, we have used a method to distinguish Mn exposure experienced in the 2nd trimester from that experienced in the 3rd trimester. We observed a significant association (rspearman=0.36, p=0.001, n=77) between Mn levels in the entire prenatally formed dentine [as 55Mn:43Ca area under the curve (AUC)] with floor dust Mn loading (µg Mn/m2 floor area) and a stronger relationship with Mn levels in dentine formed only in the 2nd trimester (rspearman=0.40; p=0.0005; n=72), likely because dust samples were collected in the 2nd trimester. We have also compared Mn levels in cord blood and mantle dentine. While there was no significant association of 55Mn:43Ca AUC of all prenatal sampling points with cord blood Mn (rspearman=- 0.01; p=0.99), 55Mn:43Ca in the sampling point immediately adjacent to the neonatal line in each tooth showed a significant positive correlation with cord blood Mn (rspearman=0.70; p=0.003; n=16). These findings were published in Environmental Science & Technology (Arora, et al., 2012).
 
PBDEs and DDT/E: Dr. Andreas Sjödin at the CDC in Atlanta attempted to measure PBDEs and DDT in anonymous deciduous teeth collected from patients demographically similar to the CHAMACOS cohort. Using whole tooth digestion, neither PBDEs nor DDT were detected. Additional anonymous deciduous teeth were obtained from a local clinic. Dr. Arora has extracted the dentine from another set of teeth to determine if more sensitive analyses to measure organochlorine (OC) compounds (i.e., DDT) are feasible.
 
Specific Aim 2: To determine the relationship between Mn, PBDE, and DDT/E levels in teeth with other relevant biological measures. (N~50 children participating since birth.) Laboratory measurements of Mn have been completed for 330 biological samples, including 202 whole blood samples (maternal blood, cord blood, child’s blood), and 128 urine samples (maternal at 26 wk gestation and child at 24 months) by Dr. Smith at the University of California, Santa Cruz (UCSC). Results of our comparison between Mn levels in teeth and other biological samples were presented at the International Society of Exposure Science conference in October 2012 by Dr. Bradman. Consistent with previous studies, we observed significantly higher (p<0.01) Mn concentrations in maternal blood at delivery than at 26 weeks gestation, higher levels in cord blood than maternal delivery blood, and higher concentrations in cord blood than children’s blood at 24 months. The Spearman correlation between Mn levels in teeth was strongest between 3rd trimester dentin and cord blood (ρ=0.31, p<0.05), again supporting the temporal specificity of Mn measurements in teeth. We did not find any significant differences in Mn urine concentrations over time and did not observe significant correlations between Mn levels in teeth and urine, suggesting that urinary concentrations are not a useful measure of environmental Mn exposure.
 
Specific Aim 3: To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth, hair and child blood. Mn in dust: Measurements of Mn in house dust have been completed by Dr. Smith at UCSC for all 475 household dust samples with 385 unique residences and 90 repeat samples collected approximately 9 months later. We are completing analyses to identify the determinants of Mn in house dust. The strongest correlation between Mn concentrations in house dust and agricultural use of maneb and mancozeb were observed for applications within 1,000 meters of the home during the 30 days prior to dust sample collection. In multivariate models, the number of farmworkers in the home and the amount of agricultural Mn pesticide use were significant determinants of both Mn dust concentrations and floor dust Mn loadings. Mn levels were also higher in homes that were built on Antioch Loam soil versus other soil types, less clean, and in homes with less educated mothers (p<0.01). For the 90 homes with two measurements of Mn in house dust collected 9 months apart, the intra-class correlation coefficient was 0.6 indicating moderate correlation of Mn concentrations over time. We observed significant (p=0.03) global spatial autocorrelation of Mn concentrations at 1,000 meters using Moran’s I, but no spatial autocorrelation of Mn dust loading. We are currently evaluating the relationship with precipitation and modified agricultural pesticide use near the home based on wind speed and direction during the month before sample collection. A manuscript is in preparation.
 
Mn in teeth: We presented our findings on determinants of Mn levels in teeth at the International Society of Exposure Science conference in October, 2012 and have submitted a manuscript to Environmental Science and Technology. In multivariate regression models, we found that maternal agricultural work during pregnancy, the number of farm workers storing their shoes in the home, agricultural applications of Mn-containing fungicides within 3 km of the mother’s residence during the 2nd and 3rd trimesters of pregnancy, residence built on Antioch Loam soil and Mn dust loading (µg/g of dust) were significant determinants (p<0.1) of Mn levels in prenatal dentine. Multivariate regression models explained 22-29% of the variability in Mn levels in prenatal dentine. Future analyses will utilize hierarchical models to evaluate the relationship between predictors of exposure and prenatal and postnatal Mn levels in deciduous teeth.
 
Mn in hair: In anticipation of using hair Mn levels as an exposure biomarker, and the absence of a validated methodology for the accurate determination of hair Mn without external contamination, we developed and fully validated a methodology for the cleaning and analyses of hair Mn, showing in the process that prior published studies of hair Mn are likely erroneous (Eastmann, et al., 2013). We have collected and shipped hair samples from 455 children (145 boys and 310 girls) to Dr. Smith at UCSC for analysis, which is in-progress.
 
Specific Aim 4: To identify population correlates of PBDEs and DDT/E exposure in 9-year-old boys. CDC analyzed 308 CHAMACOS blood samples for PBDEs and DDT/E and we have started developing models to identify correlates of exposure and to back-extrapolate PBDE levels to the prenatal period. The PBDE and DDT measurements are complete. Dr. Andreas Sjödin will be lead author on an article examining population correlates of PBDE and DDT/E exposures in 9-year-olds.
 
Additionally, the Exposure Project B is developing estimates of maternal PBDE and DDT/E levels in CHAM 2 mom’s for use in statistical analyses evaluating health effects in Project A. These back calculation methods use CHAM1 participant results as a model to identify the best way to estimate the CHAM2 maternal levels during their pregnancies. Preliminary back-extrapolation models completed by Dr. Marc-André Verner for PBDEs have R2 values ranging from 0.46 to 0.80. The higher R2 values are for statistical models (versus PBPK approaches).
 
Significance: Measurements of Mn in deciduous tooth cross-sections were validated as a new biomarker of Mn exposure in children and agricultural use of Mn fungicides was identified as a source of prenatal exposure, substantially contributing to the field of metal exposure and environmental epidemiology. We will utilize a recently developed methodology for the accurate assessment of hair Mn levels as a biomarker of environmental Mn exposure in a large sample of children. Agricultural use of Mn-containing fungicides is the main source of Mn in California and nationally. Determining whether these pesticides contribute to human exposures and health effects is an important public health issue. Studies of PBDE exposure will inform researchers about the impact of California’s unique flammability laws.

Future Activities:

In the next year, measurements of Mn in hair will be completed. We will complete analyses of predictors of Mn in house dust and correlates of PBDE and DDT/E exposure. We expect to publish at least four manuscripts this year, one on predictors of Mn in dust, one examining the interrelationships of Mn in biological samples, one on the best method to back-estimate maternal PBDE and DDT/E levels in adult women, and another on correlates of PBDEs and DDT/E in 9-year old boys.


Journal Articles on this Report : 10 Displayed | Download in RIS Format

Other subproject views: All 103 publications 38 publications in selected types All 37 journal articles
Other center views: All 666 publications 138 publications in selected types All 137 journal articles
Type Citation Sub Project Document Sources
Journal Article Arora M, Bradman A, Austin C, Vedar M, Holland N, Eskenazi B, Smith DR. Determining fetal manganese exposure from mantle dentine of deciduous teeth. Environmental Science & Technology 2012;46(9):5118-5125. R834513 (2010)
R834513 (2012)
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  • Journal Article Austin C, Smith TM, Bradman A, Hinde K, Joannes-Boyau R, Bishop D, Hare DJ, Doble P, Eskenazi B, Arora M. Barium distributions in teeth reveal early-life dietary transitions in primates. Nature 2013;498(7453):216-219. R834513 (2013)
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  • Journal Article Beamer PI, Canales RA, Ferguson AC, Leckie JO, Bradman A. Relative pesticide and exposure route contribution to aggregate and cumulative dose in young farmworker children. International Journal of Environmental Research and Public Health 2012;9(1):73-96. R834513 (2013)
    R834513 (Final)
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  • Journal Article Bradman A, Castorina R, Sjodin A, Fenster L, Jones RS, Harley KG, Chevrier J, Holland NT, Eskenazi B. Factors associated with serum polybrominated diphenyl ether (PBDE) levels among school-age children in the CHAMACOS cohort. Environmental Science & Technology 2012;46(13):7373-7381. R834513 (2012)
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  • Journal Article Bradman A, Kogut K, Eisen EA, Jewell NP, Quiros-Alcala L, Castorina R, Chevrier J, Holland NT, Barr DB, Kavanagh-Baird G, Eskenazi B. Variability of organophosphorous pesticide metabolite levels in spot and 24-hr urine samples collected from young children during 1 week. Environmental Health Perspectives 2013;121(1):118-124. R834513 (2011)
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  • Journal Article Eastman RR, Jursa TP, Benedetti C, Lucchini RG, Smith DR. Hair as a biomarker of environmental manganese exposure. Environmental Science & Technology 2013;47(3):1629-1637. R834513 (2012)
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  • Journal Article Gunier RB, Bradman A, Jerrett M, Smith DR, Harley KG, Austin C, Vedar M, Arora M, Eskenazi B. Determinants of manganese in prenatal dentin of shed teeth from CHAMACOS children living in an agricultural community. Environmental Science & Technology 2013;47(19):11249-11257. R834513 (2013)
    R834513 (2014)
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  • Journal Article Huen K, Bradman A, Harley K, Yousefi P, Boyd Barr D, Eskenazi B, Holland N. Organophosphate pesticide levels in blood and urine of women and newborns living in an agricultural community. Environmental Research 2012;117:8-16. R834513 (2010)
    R834513 (2011)
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  • Journal Article Quiros-Alcala L, Bradman A, Smith K, Weerasekera G, Odetokun M, Barr DB, Nishioka M, Castorina R, Hubbard AE, Nicas M, Hammond SK, McKone TE, Eskenazi B. Organophosphorous pesticide breakdown products in house dust and children's urine. Journal of Exposure Science & Environmental Epidemiology 2012;22(6):559-568. R834513 (2012)
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  • Journal Article Quiros-Alcala L, Eskenazi B, Bradman A, Ye X, Calafat AM, Harley K. Determinants of urinary bisphenol A concentrations in Mexican/Mexican-American pregnant women. Environment International 2013;59:152-160. R834513 (2013)
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  • Supplemental Keywords:

    DDT, DDE, PBDEs, flame retardants, manganese, maneb, mancozeb, pesticides, exposure assessment, biomonitoring, house dust, dust loading, teeth, blood, urine measurements, RFA, Health, Scientific Discipline, INTERNATIONAL COOPERATION, Health Risk Assessment, Children's Health, Environmental Policy, Biology, pesticide exposure, farmworkers, flame retardants, PBDE, children's vulnerablity, neurochemical effects, harmful environmental agents, biological markers, agricultural community

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    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2014 Progress Report
  • 2015 Progress Report
  • Final

  • Main Center Abstract and Reports:

    R834513    Center for the Health Assessment of Mothers and Children of Salinas - UC Berkeley School of Public Health: CHAMACOS Office, Berkeley, CA

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834513C001 CHAMACOS Cohort Project: Pesticides and PBDE on Neurobehavior and Puberty
    R834513C002 Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
    R834513C003 Epigenetics Project
    R834513C004 Community Outreach and Translation Core