Grantee Research Project Results

2011 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 Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
Investigators: Eskenazi, Brenda , Holland, Nina T. , Sjodin, Andreas , Bradman, Asa , Smith, Donald , Eisen, Ellen , Molitor, John , Harley, Kim , Arora, Manish , Jerrett, Michael
Current Investigators: Eskenazi, Brenda , Harley, Kim , Holland, Nina T. , Jerrett, Michael , Sjodin, Andreas , Arora, Manish , Smith, Donald , Eisen, Ellen , Molitor, John , Hubbard, Alan , Lustig, Robert
Institution: University of California - Berkeley
EPA Project Officer: Hahn, Intaek
Project Period: August 1, 2009 through July 31, 2014 (Extended to July 31, 2017)
Project Period Covered by this Report: August 1, 2010 through May 31,2011
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Measurements of Mn in deciduous tooth cross sections will be validated as a new biomarker of Mn exposure in children, substantially contributing to the field of metal exposure and environmental epidemiology. Agricultural use of Mn-containing fungicides is a potential 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 flammability laws.

Exposure to these chemicals is widespread. PBDEs have been detected in 97% of the U.S. population. Exposure to background levels of DDE is also ubiquitous in the U.S. and exposure to DDT can be very high in developing countries where DDT is increasingly used for malaria control. In the US, exposure to Mn occurs from industrial sources, but little research has been conducted on agricultural sources, even though approximately 9 million pounds of the manganese-containing fungicides mancozeb and maneb are applied annually in the U.S. These exposures may be particularly relevant in agricultural communities in California which have the potential for high exposure to all three compounds.

In Project B, we will examine novel methods of examining prenatal exposure to Mn, PBDE, and DDT/E compounds using shed deciduous teeth and GIS methods with remote sensing.

The specific aims of Project B have not changed this year.

To measure Mn, PBDEs, and DDT/E in shed deciduous teeth. (Population: CHAMACOS children participating since birth.)
To determine the relationship between Mn, PBDE, and DDT/E levels in teeth with other relevant biological measures.
To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth and child blood.
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 >30 teeth collected from the CHAMACOS cohort. Measurements employing LA/ICP/MS were made at ~20 analysis points spanning the neonatal line for both enamel and dentine tooth regions using 25 µm diameter laser ‘spot sizes’ at measurement intervals of ~200 µm. 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 2^nd trimester from that experienced in the 3^rd trimester. We have examined the association of sampling points in the entire prenatally formed dentine with floor dust Mn loading (µg Mn/m² floor area). Because dust samples were collected in the 2^nd trimester, we also undertook analyses comparing dust Mn loading with Mn levels in dentine formed only in the 2^nd trimester. We observed that the association of Mn loading in house dust was stronger with ⁵⁵Mn:⁴³Ca AUC of the 2^nd trimester dentine sampling points (r_spearman=0.60; p=0.0006; n=29) than with all prenatal sampling points (r_spearman=0.53, p=0.002, n=31).

We have also compared Mn levels in cord blood and mantle dentine. There was no significant association of ⁵⁵Mn:⁴³Ca AUC of all prenatal sampling points with cord blood Mn (r_spearman=-0.11; p=0.64; n=22). However, ⁵⁵Mn:⁴³Ca in the sampling point immediately adjacent to the neonatal line in each tooth showed a significant positive correlation with cord blood Mn (r_spearman=0.50; p=0.02; n=22). Given the short half-life of Mn in blood (approximately 4 days) and the marked variations in circulating levels during pregnancy, it is likely that only mantle dentine closest to the neonatal line reflects Mn levels in fetal circulation at birth.

To further illustrate the utility of this biomarker, we examined detailed data on two children with markedly different levels of Mn in house floor dust. Dentine Mn levels in the child from the home with greater floor dust Mn load were clearly higher than the child from the low dust-Mn household. These results demonstrate our capability to make these measurements, and are consistent with the hypothesis that higher environmental Mn concentrations are associated with higher Mn exposure. We are in the process of submitting a paper describing the methods and developing plans to measure Mn in all remaining teeth (see below).

Challenges: No new challenges have arisen in the last year. Per our progress report last year, Dr. Arora is now conducting measurements of Mn in teeth at the University of Sydney in Australia. Dr. Smith continues to collaborate with Dr. Arora to ensure the quality of the data.

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, PBDEs or DDT were not detected. Additional anonymous deciduous teeth were obtained from a local clinic. Dr. Arora is extracting the dentine from these teeth to determine if more sensitive analyses to measure organochlorine (OC) compounds (i.e., DDT) are feasible.

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.)

Mn has been measured in the teeth of 31 participants to date. Additional teeth and appropriate biological samples have been shipped to Dr. Smith at UCSC. The laboratory analyses are in progress. Statistical analyses will be conducted when the laboratory measurements are completed. As noted above, Dr. Sjödin was not able to measure PBDEs and DDT, but is investigating other methods.

3. To quantify the contribution of agricultural pesticide use to Mn levels in house dust, teeth 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. Among the unique residences, the geometric mean concentration was 150 µg Mn/g dust and the geometric mean loading was 403 µg Mn/m² floor area. We have linked the GPS coordinates of individual homes to Pesticide Use Reporting data for maneb and mancozeb, the two widely used Mn-containing pesticide used in the Salinas Valley, and have begun to identify the determinants of Mn in house dust incorporating data on wind speed and direction. 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. Both dust Mn concentrations and floor dust Mn loadings were significantly higher in homes where farmworkers lived than in those without farmworkers, and in homes that were within 1,000 meters of agricultural applications of maneb or mancozeb during the previous 30 days than those without (Table 1). 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.

A total of 156 teeth have been shipped to Dr. Arora for Mn analysis. Measurements are in progress.

Link between Maneb and Mn in blood: Blood collection from 9 year old children is completed.

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

Blood collection from 9-year-old children is completed. Once Dr. Smith’s laboratory is finished completing Mn measurement for biological samples related to Aim 2, blood samples collected from 9-year-OLD CHAMACOS children will be shipped to UCSC for Mn analysis.

Other Studies

DAPS in child urine: We recently published an article describing organophosphate (OP) pesticide metabolite dialkyl phosphate (DAP) levels in CHAMACOS children at 6, 12, and 24 months.
DAPs in the environment (EPA STAR Fellowship): Measurements of DAPs in urine may come from OP pesticide in child or intake of preformed DAPs. We measured preformed DAPs in dust. DAPs were present in dust but did not significantly contribute to measured DAPs in urine. A second manuscript is in review.
PBDEs in Pregnant women and children (NIEHS): An article we recently published in EHP showed that PBDE levels in CHAMACOS children were seven times higher than similar children living in Mexico, and three times higher than levels in their mothers. The higher exposures were likely related to the use of chemical flame retardants to meet unique California flammability laws.

Future Activities:

The timeline for this project has not changed. In the next year, measurements of Mn in teeth, and for a subset, maternal and child blood and urine and breastmilk, will be completed. We will begin analyses examining the interrelationships of Mn in teeth and other biological samples as well as completing the analyses of predictors of Mn in house dust. We will also complete analysis of Mn and PBDEs in blood from CHAMACOS nine year old children. We expect to publish at least three manuscripts this year, one on predictors of Mn in dust, another one validating Mn measurements in teeth, and one examining predictors of Mn levels in teeth.

Journal Articles on this Report : 8 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 108 publications	43 publications in selected types	All 42 journal articles
Other center views:	All 697 publications	170 publications in selected types	All 169 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Bradman A, Castorina R, Barr DB, Chevrier J, Harnly ME, Eisen EA, McKone TE, Harley K, Holland N, Eskenazi B. Determinants of organophosphorus pesticide urinary metabolite levels in young children living in an agricultural community. International Journal of Environmental Research and Public Health 2011;8(4):1061-1083.	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R834513C003 (2010) R834513C003 (2011) R834513C003 (Final) R831710 (Final) R832734 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: MDPI-Full-Text HTML Exit Abstract: MDPI-Abstract Exit Other: MDPI-Full-Text PDF Exit
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) R834513 (2012) R834513 (2013) R834513 (Final) R834513C002 (2011) R834513C002 (2012) R834513C002 (2013) R834513C003 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract & Full Text HTML
Journal Article	Castorina R, Bradman A, Fenster L, Barr DB, Bravo R, Vedar MG, Harnly ME, McKone TE, Eisen EA, Eskenazi B. Comparison of current-use pesticide and other toxicant urinary metabolite levels among pregnant women in the CHAMACOS cohort and NHANES. Environmental Health Perspectives 2010;118(6):856-863.	R834513 (2010) R834513 (2011) R834513 (Final) R834513C002 (2010) R834513C002 (2011) R834513C003 (Final) R831710 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract and Full Text HTML
Journal Article	Castorina R, Bradman A, Sjodin A, Fenster L, Jones RS, Harley KG, Eisen EA, Eskenazi B. Determinants of serum polybrominated diphenyl ether (PBDE) levels among pregnant women in the CHAMACOS cohort. Environmental Science & Technology 2011;45(15):6553-6560.	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C001 (2012) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R834513C003 (2012) R834513C003 (Final) R831710 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ResearchGate-Full Text PDF Exit Abstract: ACS-Abstract Exit Other: ACS-Full Text PDF Exit
Journal Article	Eskenazi B, Fenster L, Castorina R, Marks AR, Sjodin A, Rosas LG, Holland N, Guerra AG, Lopez-Carrillo L, Bradman A. A comparison of PBDE serum concentrations in Mexican and Mexican-American children living in California. Environmental Health Perspectives 2011;119(10):1442-1448.	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C001 (2012) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R834513C003 (2010) R834513C003 (2011) R831710 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHP-Full Text PDF Abstract: EHP-Abstract & Full Text HTML
Journal Article	Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Eskenazi B. Concentrations and loadings of polybrominated diphenyl ethers in dust from low-income households in California. Environment International 2011;37(3):592-596.	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513C001 (2010) R834513C001 (2011) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R831710 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
Journal Article	Quiros-Alcala L, Bradman A, Nishioka M, Harnly ME, Hubbard A, McKone TE, Ferber J, Eskenazi B. Pesticides in house dust from urban and farmworker households in California: an observational measurement study. Environmental Health 2011;10:19 (15 pp.).	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C002 (2010) R834513C002 (2011) R834513C002 (2012) R831710 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: EHJ-Full Text HTML Exit Abstract: EHJ-Abstract Exit Other: EHJ-Full Text PDF Exit
Journal Article	Weldon RH, Webster M, Harley KG, Bradman A, Fenster L, Davis MD, Hubbard A, Barr DB, Holland N, Eskenazi B. Serum persistent organic pollutants and duration of lactation among Mexican-American women. Journal of Environmental and Public Health 2010;2010:861757 (11 pp.).	R834513 (2010) R834513 (2011) R834513 (2012) R834513 (2013) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2010) R834513C001 (2011) R834513C002 (2010) R834513C002 (2011) R834513C003 (2010) R834513C003 (2011) R831710 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Hindawi-Full Text HTML Exit Abstract: Hindawi-Abstract Exit Other: Hindawi-Full Text PDF Exit

Supplemental Keywords:

Exposure assessment, environmental, disease, toxin, health effects, child health, biomarkers, epigenetic, DNA methylation, reproductive health, neurobehavioral health, pubertal onset, metabolic syndrome, obesity, cognition, attention, memory, motor, executive function, social cognition, infants, children, latino, farmworker, agriculture, pesticide, fungicide, PBDE, DDT, Mn, California, CA, Salinas Valley, community-based, deciduous teeth, back-extrapolation, GIS, maternal, international cooperation, health, biology, health risk assessment, children's health, environmental policy, neurological development, farmworkers, harmful environmental agents, flame retardants, agricultural community, pesticide exposure, neurochemical effects, biological markers, children's vulnerablity, RFA, Scientific Discipline, Health, INTERNATIONAL COOPERATION, Health Risk Assessment, Children's Health, Environmental Policy, Biology, farmworkers, pesticide exposure, flame retardants, PBDE, children's vulnerablity, neurochemical effects, harmful environmental agents, biological markers, agricultural community

Relevant Websites:

http://cerch.org/ Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R834513 Center for Research on Early Childhood Exposure and Development in Puerto Rico

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

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.