Grantee Research Project Results
2014 Progress Report: Project B: Exposure Project: Mn, DDT/E and PBDE Exposure to Farmworker Children
EPA Grant Number: R834513C002Subproject: 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 , Bradman, Asa , Jerrett, Michael , Molitor, John , Holland, Nina T. , Harley, Kim , Sjodin, Andreas , Smith, Donald , Arora, Manish
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 , University of California - Santa Cruz , Centers for Disease Control and Prevention
Current 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, 2009 through July 31,2014
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:
In Project B, we are studying novel methods of examining prenatal exposure to Mn, PBDE, and DDT/E compounds. For exposure to Mn, we are measuring Mn levels in shed deciduous teeth and in hair collected when the children were 10.5 years of age. For PBDEs and DDT/E, we are developing models to back-extrapolate prenatal exposure levels from 9-year measured levels and other determinants of exposure.
Progress Summary:
Specific Aim 1: To measure Mn, PBDEs, and DDT/E in shed deciduous teeth (Population: CHAMACOS children participating since birth)
Mn: We have successfully developed a method for measuring Mn in human teeth by laser ablation inductively coupled plasma 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 second trimester from that experienced in the third 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 second trimester (rspearman = 0.40; p = 0.0005; n = 72), likely because dust samples were collected in the second trimester. We also have compared Mn levels in cord blood and mantle dentine. Although 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 dentin from another set of teeth to determine if more sensitive analyses to measure organochlorine (OC) compounds (i.e., DDT) or PBDEs are feasible.
Specific Aim 2: To determine the relationship between Mn, PBDE, and DDT/E levels in teeth with other relevant biological measures
Laboratory measurements of Mn have been completed for 330 biological samples, including 202 whole blood samples (maternal blood, cord blood, child 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). We analyzed Mn in pre- and postnatal dentin and enamel in deciduous teeth from 62 children using LA/ICP/MS. We also measured Mn concentrations in maternal, cord, and child blood, and maternal and child urine and examined the interrelationships of Mn levels in all matrices.
Mn levels (Mn:Ca ratio) were higher in prenatal than postnatal dentin (geometric mean [GM] = 0.51 vs. 0.16, p < 0.0001). Maternal blood Mn concentrations increased from 26 weeks gestation to delivery (GM = 14.6 to 20.7 μg/L, p = 0.001) and child blood Mn concentrations decreased from cord blood to 24 month blood samples (39.9 vs. 25.0 μg/L, p = 0.005). Mn levels in tooth dentin during the third trimester were positively correlated with Mn concentrations in cord blood (rs = 0.31), while there was a negative correlation between prenatal Mn levels in enamel and Mn concentrations in maternal blood at 26 weeks gestation (rs = -0.36). 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.
We observed significantly higher (p < 0.05) levels of Mn in prenatal dentin, prenatal maternal blood, and 24-month urine from children if there was a farmworker living in the home during the corresponding time period compared to no farmworker living in the home. Prenatal Mn levels in dentin and cord blood also were correlated with Mn loading in prenatal house dust samples (rs = 0.27 and 0.29, respectively; p < 0.1). Tooth dentin and blood Mn concentrations had the strongest associations with potential sources of Mn exposure in the home.
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: We collected house dust samples from 378 residences enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study with a second sample collected approximately 9 months later from 90 of the residences. House dust samples were analyzed for Mn using ICP optical emission spectroscopy. Information from interviews, home inspections, and pesticide use reports was used to identify potential predictors of Mn dust concentrations and loadings. Mn was detectable in all dust samples. The median Mn concentration was 171 μg/g and median Mn loading was 1,910 μg/m2 at first visit. In multivariable models, Mn dust concentrations and loadings increased with the number of farmworkers in the home and the amount of agricultural Mn fungicides applied within three kilometers of the residence during the month prior to dust sample collection (see Figure 1). Dust concentrations of Mn and other metals (lead, cadmium and chromium) were higher in residences located in the southern Salinas Valley compared with those located in other areas of the Salinas Valley. Dust loadings of Mn and other metals also were higher in residences located on Antioch Loam soil than other soil types, and in homes with poor or average housekeeping practices. Agricultural use of Mn containing fungicides was associated with Mn dust concentrations and loadings in nearby residences and farmworker homes. Housekeeping practices and soil type at residence also were important factors related to dust metal concentrations and loadings. A manuscript was submitted to Science of The Total Environment and we have responded to comments from reviewers.
Figure 1. Percentage change in manganese dust loading (μg/m2) for select predictor variables estimated from multivariable mixed effects models (n=464).
Mn in teeth: Participants in our analysis included 207 children enrolled in the CHAMACOS study. Mn was measured in teeth using LA/ICP/MS. Our purpose was to determine environmental and lifestyle factors related to prenatal Mn levels in shed teeth. We found that storage of farmworkers' shoes in the home, maternal farm work, agricultural use of Mn-containing fungicides within 3 km of the residence, residence built on Antioch Loam soil and Mn dust loading (μg/m2 of floor area) during pregnancy were associated with higher Mn levels in prenatal dentin (p < 0.05). Maternal smoking during pregnancy was inversely related to Mn levels in prenatal dentin (p < 0.01). Multivariable regression models explained 22-29% of the variability of Mn in prenatal dentin (Table 1). Our results suggest that Mn measured in prenatal dentin provides retrospective and time-specific levels of fetal exposure resulting from environmental and occupational sources.
| Children with Tooth Mn Levels | Children with Tooth and Dust Mn Levels | |||||
| Predictor Variable | % Changeb (95% CI) | p-value | Partial r2 (%) | % Changeb (95% CI) | p-value | Partial r2 (%) |
| Maternal farmwork | 10.1 (0.1, 21.3) | 0.05 | 1.8 | 15.8 (1.9, 31.6) | 0.03 | 3.9 |
| (Prenatal yes vs. no) | ||||||
| Farmworker shoes in | ||||||
| home | 8.1 (4.3, 12.0) | <0.001 | 8.4 | 6.4 (1.5, 11.4) | 0.01 | 5.2 |
| (Prenatal per worker) | ||||||
| Agricultural fungicide | ||||||
| use prenatal within 3 | ||||||
| km (per IQRc = 809 kg ) | 4.9 (0.9, 9.1) | 0.02 | 2.8 | 3.4 (-1.6, 8.6) | 0.19 | 1.4 |
| Soil type | 15.1 (4.6, 26.6) | 0.004 | 4.0 | 20.7 (6.3, 37.1) | 0.004 | 6.4 |
| (Antioch Loam vs. | ||||||
| other) | ||||||
| Mother smoked | -33.8 (-46.6, -18.0) | <0.001 | 6.7 | -40.3 (-55.3, -20.2) | 0.001 | 9.0 |
| (Prenatal yes vs. no) | ||||||
| Mn dust loading (per IQRc = 1465 µg/m2) | - | - | 3.3 (0.3, 6.4) | 0.03 | 3.6 | |
| R2 for Model | 22% | 29% | ||||
a Prenatal = 2nd and 3rd trimesters. b Percent change = (exp(β)-1)*100; c IQR = interquartile range.
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 analysis of hair Mn, showing in the process that prior published studies of hair Mn are likely erroneous (Eastmann, et al., 2013). We have collected hair samples from 455 children (145 boys and 310 girls). Dr. Smith at UCSC has analyzed samples from 136 participants. Preliminary analyses indicate that hair Mn concentrations were not related to baseline maternal demographics or the use of hair care products prior to sample collection. In preliminary analyses, we did not observe an association between hair Mn concentrations and 10.5 year IQ in models adjusted for child's exact age, maternal education, poverty status and HOME score.
Specific Aim 4: To identify population correlates of PBDEs and DDT/E exposure in 9-year-old boys
CDC has analyzed 308 CHAMACOS blood samples for PBDEs and DDT/E in mothers and children from the 9-year visit. Dr. Andreas Sjödin will be lead author on the manuscript examining population correlates of PBDE and DDT/E exposures in 9-year-olds.
Back-extrapolation of DDT/E and PBDEs: We evaluated three back calculation modeling approaches (PBPK, deletion substitution algorithms, and SuperLearner) in study population subsets where serum levels were measured in mothers at 26 weeks of pregnancy and 9 years after delivery in mothers (n = 94), children (n = 161), or both mothers and children (n = 89). Model performance was assessed using the root mean squared error (RMSE) and coefficient of determination (R2) of log10-transformed back-extrapolated versus measured levels. For all compounds and subsets, SuperLearner outperformed the other approaches with RMSEs and R2s ranging from 0.100.31 log10 ng/g and 0.580.97, respectively. Typically, model RMSEs were lower and R2s were higher for p,p-DDT/E than PBDE congeners, and estimations using maternal levels were more accurate compared to child levels. The pharmacokinetic model performed well when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives such as p,p-DDE and BDE-153 (RMSEs = 0.21 and 0.28 log10 ng/g and R2s = 0.88 and 0.57, respectively). Results demonstrate the ability to accurately back-extrapolate prenatal levels from maternal levels 9 years after delivery, with SuperLearner performing the best based on our fit criteria.
Other Studies
- DAPs in child urine: A manuscript examining changes in pesticide excretion during organic food intake is in submission.
- BPA: An article on determinants of BPA exposure in pregnant women was accepted by Environment International (Quiros-Alcala, et al., 2014).
- Within and between subject variability: Dr. Bradman, et al., published a paper in Environmental Health Perspectives examining within and between subject variability in organophosphate metabolite excretion in young children.
- Environmental Quality in Child Care: Dr. Bradman published two studies examining environmental quality in child care, one focusing on flame retardants and one on phthalates.
- Organophosphate levels and PON1 in blood: Dr. Karen Huen (former graduate student with us) published a study reporting on chlorpyrifos and diazinon levels in maternal and infant blood and PON1 status.
- Dietary transitions in a Neanderthal infant: Dr. Manish Arora with Drs. Eskenazi and Bradman and other scientists, published a paper in Nature showing breast feeding transitions in a Neanderthal infant. The study used teeth and data from the CHAMACOS cohort to validate the method applied to a fossil Neanderthal tooth.
Future Activities:
In the next year, we will complete analyses of correlates of PBDE and DDT/E exposure. We expect to publish at least three manuscripts this year, one examining the interrelationships of Mn in biological samples (in review by co-authors), one on the best methods to back-estimate maternal PBDE and DDT/E levels in adult women (near completion), and another on correlates of PBDEs and DDT/E in 9-year old boys. Future analyses also will utilize hierarchical models to evaluate the relationship between predictors of exposure and prenatal and postnatal Mn levels in deciduous teeth.
Journal Articles on this Report : 18 Displayed | Download in RIS Format
| Other subproject views: | All 108 publications | 43 publications in selected types | All 42 journal articles |
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| Other center views: | All 697 publications | 170 publications in selected types | All 169 journal articles |
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Bradman A, Castorina R, Gaspar F, Nishioka M, Colon M, Weathers W, Egeghy PP, Maddalena R, Williams J, Jenkins PL, McKone TE. Flame retardant exposures in California early childhood education environments. Chemosphere 2014;116:61-66. |
R834513 (2014) R834513C002 (2014) R834513C003 (Final) |
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Bradman A, Quiros-Alcala L, Castorina R, Schall RA, Camacho J, Holland NT, Barr DB, Eskenazi B. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environmental Health Perspectives 2015;123(10):1086-1093. |
R834513 (2014) R834513 (2016) R834513C002 (2014) R834513C002 (2015) R834513C002 (2016) R834513C003 (Final) |
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Dannemiller KC, Mendell MJ, Macher JM, Kumagai K, Bradman A, Holland N, Harley K, Eskenazi B, Peccia J. Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development. Indoor Air 2014;24(3):236-247. |
R834513 (2014) R834513 (2015) R834513C001 (2015) R834513C002 (2014) |
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Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environmental Health Perspectives 2016;124(6):822-830. |
R834513 (2014) R834513 (2015) R834513C001 (2014) R834513C001 (2015) R834513C002 (2014) |
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Eskenazi B, Bradman A, Finkton D, Purwar M, Noble JA, Pang R, Burnham O, Cheikh Ismail L, Farhi F, Barros FC, Lambert A, Papageorghiou AT, Carvalho M, Jaffer YA, Bertino E, Gravett MG, Altman DG, Ohuma EO, Kennedy SH, Bhutta ZA, Villar J, International Fetal and Newborn Growth Consortium for the 21st Century. A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project. BJOG: An International Journal of Obstetrics & Gynaecology 2013;120(Suppl 2):129-138. |
R834513 (2014) R834513C002 (2014) |
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Eskenazi B, Quiros-Alcala L, Lipsitt JM, Wu LD, Kruger P, Ntimbane T, Nawn JB, Bornman R, Seto E. mSpray: a mobile phone technology to improve malaria control efforts and monitor human exposure to malaria control pesticides in Limpopo, South Africa. Environment International 2014;68:219-226. |
R834513 (2014) R834513C002 (2014) |
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Gaspar FW, Castorina R, Maddalena RL, Nishioka MG, McKone TE, Bradman A. Phthalate exposure and risk assessment in California child care facilities. Environmental Science & Technology 2014;48(13):7593-7601. |
R834513 (2014) R834513C002 (2014) R834513C002 (2015) |
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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) R834513 (Final) R834513C002 (2013) R834513C002 (2014) R826709 (2002) |
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Gunier RB, Mora AM, Smith D, Arora M, Austin C, Eskenazi B, Bradman A. Biomarkers of manganese exposure in pregnant women and children living in an agricultural community in California. Environmental Science & Technology 2014;48(24):14695-14702. |
R834513 (2011) R834513 (2013) R834513 (2014) R834513 (2015) R834513 (Final) R834513C002 (2014) R834513C002 (2015) R834513C004 (2011) R826709 (2002) |
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Gunier RB, Jerrett M, Smith DR, Jursa T, Yousefi P, Camacho J, Hubbard A, Eskenazi B, Bradman A. Determinants of manganese levels in house dust samples from the CHAMACOS cohort. Science of the Total Environment 2014;497-498:360-368. |
R834513 (2012) R834513 (2013) R834513 (2014) R834513 (2015) R834513 (Final) R834513C002 (2010) R834513C002 (2012) R834513C002 (2014) R834513C002 (2015) |
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Gunier RB, Arora M, Jerrett M, Bradman A, Harley KG, Mora AM, Kogut K, Hubbard A, Austin C, Holland N, Eskenazi B. Manganese in teeth and neurodevelopment in young Mexican-American children. Environmental Research 2015;142:688-695. |
R834513 (2014) R834513 (2015) R834513 (2016) R834513C001 (2014) R834513C001 (2015) R834513C001 (2016) R834513C002 (2014) |
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Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. Prenatal exposure to organophosphate pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environmental Health Perspectives 2016;124(7):1084-1092. |
R834513 (2014) R834513 (2015) R834513 (2016) R834513 (Final) R834513C001 (2014) R834513C002 (2014) R834513C002 (Final) R834513C003 (Final) |
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Mora AM, van Wendel de Joode B, Mergler D, Cordoba L, Cano C, Quesada R, Smith DR, Menezes-Filho JA, Lundh T, Lindh CH, Bradman A, Eskenazi B. Blood and hair manganese concentrations in pregnant women from the Infants’ Environmental Health Study (ISA) in Costa Rica. Environmental Science & Technology 2014;48(6):3467-3476. |
R834513 (2014) R834513C001 (2014) R834513C002 (2014) R834513C002 (2015) |
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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) R834513 (2014) R834513 (Final) R834513C002 (2013) R834513C002 (2014) |
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Salvatore AL, Castorina R, Camacho J, Morga N, Lopez J, Nishioka M, Barr DB, Eskenazi B, Bradman A. Home-based community health worker intervention to reduce pesticide exposures to farmworkers’ children: a randomized-controlled trial. Journal of Exposure Science & Environmental Epidemiology 2015;25(6):608-615. |
R834513 (2014) R834513 (2015) R834513 (2016) R834513C002 (2014) R834513C002 (2015) R834513C002 (2016) R834513C004 (2015) |
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van Wendel de Joode B, Mora AM, Cordoba L, Cano JC, Quesada R, Faniband M, Wesseling C, Ruepert C, Oberg M, Eskenazi B, Mergler D, Lindh CH. Aerial application of mancozeb and urinary ethylene thiourea (ETU) concentrations among pregnant women in Costa Rica: the Infants’ Environmental Health Study (ISA). Environmental Health Perspectives 2014;122(12):1321-1328. |
R834513 (2014) R834513C002 (2014) R834513C002 (2015) |
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Verner M-A, Gaspar FW, Chevrier J, Gunier RB, Sjodin A, Bradman A, Eskenazi B. Increasing sample size in prospective birth cohorts:back-extrapolating prenatal levels of persistent organic pollutants in newly enrolled children. Environmental Science & Technology 2015;49(6):3940-3948. |
R834513 (2014) R834513 (2015) R834513C001 (2015) R834513C002 (2014) R834513C002 (2015) |
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Warner M, Mocarelli P, Brambilla P, Wesselink A, Patterson Jr. DG, Turner WE, Eskenazi B. Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion. Journal of Exposure Science & Environmental Epidemiology 2014;24(6):588-594. |
R834513 (2014) R834513C002 (2014) |
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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, farmworker, 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 communityRelevant Websites:
Center for Environmental Research and Children's Health (CERCH) Exit
Progress and Final Reports:
Original AbstractMain 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
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.