Grantee Research Project Results
Final Report: Current-Use Pesticides: Assessing Exposure and Spermatoxicity
EPA Grant Number: R832515 aka R832098Title: Current-Use Pesticides: Assessing Exposure and Spermatoxicity
Investigators: Swan, Shanna Helen , Thomas, Peter , Sparks, Amy
Institution: The University of Texas at Austin , University of Rochester , University of Iowa
Current Institution: The University of Texas at Austin , University of Iowa , University of Rochester
EPA Project Officer: Klieforth, Barbara I
Project Period: September 1, 2005 through August 31, 2010
Project Amount: $672,821
RFA: Application of Biomarkers to Environmental Health and Risk Assessment (2004) RFA Text | Recipients Lists
Research Category: Hazardous Waste/Remediation , Human Health
Objective:
Initial Objectives:
In this STAR grant, we initially proposed to examine associations between current use pesticides and semen quality by conducting additional testing in Missouri and Minnesota men and extending this analysis to Iowa men.
Revised objectives to including and BPA analyses and structural equation modeling
Due to the Center for Disease Control and Prevention’s (CDC) heavy workload, there were several years delay in obtaining pesticide results. (See annual reports). Therefore, we applied for and received permission from EPA (December 2007) to use some of the funds for other analyses. The extended aims included estimating the strength of the associations between biomarkers of BPA and semen parameters as well as developing statistical methods for examining multiple samples per man and examining effects of joint exposure to multiple chemicals (such as BPA and pesticides).
Summary/Accomplishments (Outputs/Outcomes):
Background
Prior to this grant, we had found in our multicenter study of semen quality (Study for Future Families), significant geographic variation in semen quality that could not be attributed to confounding or methodological differences between centers. We looked for environmental factors that might explain the differences in semen quality between our most rural center (Mid-Missouri, MO) and an urban center (Minneapolis, MN). Using a small sample and a nested case-control study design, we found that urinary metabolites of several current-use pesticides were significantly related to semen quality in a nested case-control study of men in MO. This study was published in 2003 and provided the rationale for the study funded by Environmental Protection Agency (EPA) Grant Number RD832515, entitled Current-Use Pesticides: Assessing Exposure and Spermatoxicity.”
Inability to obtain meaningful pesticide results
The first pesticide analyses that were conducted under this Science to Achieve Results (STAR) grant included 20 analytes on 257 men. Due to extensive delays at the CDC Pesticide Laboratory to which we had subcontracted these analyses, the first results were not received until 2008, after the close of the original project period (see earlier Annual Reports for details). However, after careful examination and analyses of these results it became evident that the analytic results sent by the CDC in 2008 were totally inconsistent with those sent from the same laboratory in 2002. For example, the percent of samples with detectable (above limit of detection) pesticide concentrations in the 2008 samples were dramatically different from those the CDC had reported for the same pesticides in 2002. The difference in populations in the 2002 and 2008 samples could not account for these differences. Thus, it was concluded that there had been significant changes in laboratory methods, contamination, or sample degradation, and it was not apparent whether the results sent in 2008 could be used at all. In addition, the distribution of creatinine values in the two time periods was totally different.
While the samples analyzed in 2002 and 2008 were not, overall, from the same men, fortunately a subset of 52 Missouri men measured in 2002 samples had been rerun in 2008. Thus, we had the opportunity to examine values in the same men and in the same urine sample (urine samples had been aliquotted in several tubes) and this provided an opportunity to examine the correlation between analytes in the two sample runs. We were extremely perturbed to see, after careful analysis, that the values obtained in 2002 and 2008 did not correlate at all (some correlations were small and positive, some near zero and some even negative). This comparison confirmed that either the 2002 data or the 2008 data (or both) were invalid.
The next step was to determine if the 2008 data could be replicated. To examine the reliability of the 2008 measurements, we sent a second aliquot of urine for 30 men whose samples had been run in 2008 to see if those values (or correlated values) could be obtained again in 2009. Although we repeatedly asked the CDC lab for these results, which we hoped would provide reassurance that the 2008 values were reliable, these results were never sent to us despite numerous phone calls and e-mails that were not returned. We continued these attempts until Dana Barr left CDC in summer 2009.
Conclusions:
We spent a huge amount of time 1) waiting for our results that were not sent until 2008, 2) discovering that (some or all) of the pesticide data were not reliable (and hence that our analyses could not be relied on or published), and then 3) then to identify which analytes or which data sets could be used. We were not able to solve the problem of why results in 2008 were so dissimilar from earlier results (even in samples from the same men). Therefore, the study aims specifically related to pesticides could not be met despite these extensive efforts. This was particularly surprising because under our earlier STAR grant (Phthalates in Pregnant Women and Children) our collaboration with the CDC was exemplary; all study aims were met, resulting in publications, which are now considered to be groundbreaking, with worldwide regulatory ramifications.
Other analyses conducted with EPA permission
BPA: Fortunately, we had obtained permission in 2007 to conduct additional analyses under this grant. We obtained BPA metabolites concentrations and creatinine values on 375 men from Antonia Calafat’s lab in December 2008. These data were analyzed in 2009. We found no significant associations between any sperm parameter or serum hormone and concentration of BPA in men’s urine. These results were published in 2010 (Mendiola J, Jorgensen N, Andersson A-M, Calafat AM, Ye X, Redmon JB, Swan SH. Are environmental levels of bisphenol A associated with reproductive function in fertile men? Environ Health Perspect 2010, doi:10.1289/ehp.1002037).
Statistical modeling: We worked with co-investigator Sally Thurston and her doctoral student, Abbie Stokes-Riner, to address several statistical issues involved in the analysis of pesticides and semen quality, as well as other environmental chemicals. The first paper to come out of this work addresses the question of whether a data set such as ours, with an unequal number of measurements per subject can utilize all samples without introducing bias. This was published in 2007 (Stokes-Riner A, Thurston SW, Brazil C, Guzick D, Liu F, Overstreet JW, Wang C, Sparks A, Redmon JB, Swan SH. One semen sample or two? Insights from a study of fertile men. J Androl 2007;28:638-643).
Abbie Stokes-Riner then developed the methods to address one of our primary aims, the use of Structural Equation Modeling to examine the effects of complex mixtures on semen quality. This formed the basis of the doctoral dissertation. Her doctorate was awarded in 2010 and these results currently are being written up for publication.
Sperm membrane progesterone receptor: One of the original aims of this grant was to measure levels of human sperm membrane progesterone receptor (hmPRα) and to examine this variable in relation to both semen parameters and levels of current-use pesticides. This assay requires that the sperm membrane be stored, and these samples were available only for 78 men from Iowa. Peter Thomas analyzed these samples using funding from this grant and we found a significant association between hmPRα-density and sperm motility. Until recently, we had hoped to be able to examine this sperm parameter in relation to current use pesticides. Once it became apparent that the pesticide data were not usable, in 2010, we began examining BPA in relation to hmPRα-density to see whether BPA concentration modified the associations we had found between hmPRα-density and sperm motility. This analysis is nearly complete and results are being written up for publication.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
| Other project views: | All 13 publications | 12 publications in selected types | All 9 journal articles |
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Jensen TK, Swan SH, Skakkebaek NE, Rasmussen S, Jorgensen N. Caffeine intake and semen quality in a population of 2,554 young Danish men. American Journal of Epidemiology 2010;171(8):883-191. |
R832515 aka R832098 (Final) |
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Mendiola J, Jorgensen N, Andersson AM, Calafat AM, Ye X, Redmon JB, Drobnis EZ, Wang C, Sparks A, Thurston SW, Liu F, Swan SH. Are environmental levels of bisphenol A associated with reproductive function in fertile men? Environmental Health Perspectives 2010;118(9):1286-1291. |
R832515 aka R832098 (2006) R832515 aka R832098 (Final) |
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Stokes-Riner A, Thurston SW, Brazil C, Guzick D, Liu F, Overstreet JW, Wang C, Sparks A, Redmon JB, Swan SH. One semen sample or two? Insights from a study of fertile men. Journal of Andrology 2007;28(5):638-643. |
R832515 aka R832098 (2006) R832515 aka R832098 (2007) R832515 aka R832098 (2008) R832515 aka R832098 (Final) |
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Supplemental Keywords:
BPA, semen quality, hmPRα density, serum hormones, latent variable model, RFA, Health, Scientific Discipline, Health Risk Assessment, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Biochemistry, Endocrine Disruptors - Human Health, pesticide exposure, altered sexual development, EDCs, endocrine disrupting chemicals, exposure studies, developmental biology, human growth and development, atrazine, agrochemicalsProgress and Final Reports:
Original AbstractThe 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.