Grantee Research Project Results

Final Report: Study of Phthalates in Pregnant Woman and Children

EPA Grant Number: R829436
Title: Study of Phthalates in Pregnant Woman and Children
Investigators: Swan, Shanna Helen , Lasley, Bill L. , Sparks, Amy , Calafat, Antonia , Redmon, Bruce , Wang, Christina , Kruse, Robin
Institution: University of Rochester , University of Iowa , University of Missouri - Columbia , Harbor-UCLA Medical Center , University of Minnesota , Centers for Disease Control and Prevention , University of California - Davis
Current Institution: University of Rochester , Centers for Disease Control and Prevention , Harbor-UCLA Medical Center , University of California - Davis , University of Iowa , University of Minnesota , University of Missouri - Columbia
EPA Project Officer: Aja, Hayley
Project Period: August 1, 2001 through January 31, 2005 (Extended to July 31, 2007)
Project Amount: $2,779,164
RFA: Endocrine Disruptors: Epidemiologic Approaches (2001) RFA Text | Recipients Lists
Research Category: Environmental Justice , Human Health , Safer Chemicals , Endocrine Disruptors

Objective:

To assess the risks posed by environmental phthalate levels to reproductive health.

Summary/Accomplishments (Outputs/Outcomes):

We have:

Measured urinary phthalate metabolites in 1008 urine samples including 343 mother’s prenatal samples, 345 mother’ s post-natal samples and 320 infant samples.
Designed and tested a protocol for an infant genital exam including, in males the measurement of anogenital distance (AGD), testicular descent and penile size, and in females clitoral index and AGD.
Trained researchers in these methods (Harvard School of Public Health, University of Washington, Karlstad University). (Results to be submitted 2009).
Conducted postnatal exams on 451 infants (including 451 first exams and 184 second exams) in our study population.
Completed the analyses of urinary metabolite concentration in relation to markers of male genital development. (Results published).
Analyzed urinary metabolite concentration in infants in relation to baby-care product use. (Results published).
Analyzed the relationship between mother’s and infant metabolite concentrations. (Results published).
Participated in EPA analysis of estimated phthalate dose to infants. (Results published).
Completed an analysis of gestational age at delivery and prenatal DEHP metabolite concentration. (Results in press).
Conducted a pilot study of gender-related play behavior in relation to prenatal phthalate exposure and analyzed these results. (Results to be submitted in 2009)
Provided assistance and testimony on these results to numerous environmental and legislative groups, which have been instrumental in federal and state phthalate legislation.

Summary of results: We demonstrated the feasibility of measuring anogenital distance (AGD) and other endpoints previously utilized primarily in toxicological studies. We showed that AGD in human infants was sexually dimorphic and could reliably be measured. We showed that urinary metabolites of prenatal DEHP and perhaps other phthalates (DEP and DBP) were significantly related AGD and that DEHP metabolites were associated with three endpoints included in the phthalate syndrome, previously identified in rodents. WE showed that joint exposure to a mixture of these chemicals is more strongly associated with these changes than the individual exposures, suggesting dose additivity. We demonstrated the ubiquitous nature of phthalates in young infants and the presence of large numbers of these chemicals above the limit of detection, even in the youngest infant (2 months). We showed a significant relationship between the number of baby products utilized by the mother and levels of several phthalates in infant urine. We have written and spoken about these results widely (as well as participating in numerous short and longer TV specials and films) and these findings have played a significant role in legislation (state, federal and international) of phthalates in children’s toys.

Conclusions:

Phthalate exposure is ubiquitous in a population-based sample of women and children (as well as men, analyzed under separate funding). Higher levels of prenatal exposure to several phthalates are associated with alterations in genital markers that are consistent with the phthalate syndrome, previously identified in rodents.

Future Activities:

Submit publication on gender-related play behavior in relation to prenatal phthalate exposure (by May 2009).
Complete analysis of joint maternal and paternal phthalate exposure in relation to male genital development and submit publication (by June 2009)
Complete manuscript on AGD measurement (by July 2009).
Complete analysis and submit manuscript on geographic differences in phthalate metabolite concentration (by August 2009)
Complete analysis of pre vs. postnatal phthalate concentration controlling for time of urine collection and submit manuscript (by September 2009).
Complete analysis of buccal smears and test for gene/phthalate interactions in effects on male AGD (late 2009).

Journal Articles on this Report : 11 Displayed | Download in RIS Format

Publications Views
Other project views:	All 41 publications	12 publications in selected types	All 11 journal articles

Publications
Type	Citation	Project	Document Sources
Journal Article	Adibi JJ, Hauser R, Williams PL, Whyatt RM, Calafat AM, Nelson H, Herrick R, Swan SH. Maternal urinary metabolites of di-(2-ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study. American Journal of Epidemology 2009;169(8):1015-1024.	R829436 (Final) R832141 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: AJE - Full Text HTML Exit Abstract: AJE - Abstract Exit Other: AJE - Full Text PDF Exit
Journal Article	Marsee K, Woodruff TJ, Axelrad DA, Calafat AM, Swan SH. Estimated daily phthalate exposures in a population mothers of male infants exhibiting reduced anogenital distance. Environmental Health Perspectives 2006;114(6):805-809.	R829436 (2005) R829436 (Final)	Abstract from PubMed Full-text: EHP Exit Other: EHP PDF Exit
Journal Article	Sathyanarayana S, Karr CJ, Lozano P, Brown E, Calafat AM, Liu F, Swan SH. Baby care products:possible sources of infant phthalate exposure. Pediatrics 2008;121(2):e260-e268.	R829436 (Final)	Abstract from PubMed Full-text: Pediatrics Exit Other: Pediatrics PDF Exit
Journal Article	Sathyanarayana S, Calafat AM, Liu F, Swan SH. Maternal and infant urinary phthalate metabolite concentrations: are they related? Environmental Research 2008;108(3):413-418.	R829436 (Final)	Abstract from PubMed Full-text: Science Direct Exit Other: Science Direct pdf Exit
Journal Article	Swan SH, Robins JM. An analysis of contaminated well water and health-effects in Woburn, Massachusetts-Comment. Journal of the American Statistical Association 1986;81(395):604-609	R829436 (Final)	Full-text: JSTOR - Full Text PDF Exit Other: Taylor & Francis - Full Text PDF Exit
Journal Article	Swan SH. Do environmental agents affect semen quality?. Epidemiology 2003;14(3):261-262.	R829436 (Final)	Abstract from PubMed Full-text: Epidemiology - Full Text HTML Exit
Journal Article	Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives 2005;113(8):1056-1061.	R829436 (2005) R829436 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Swan SH. Prenatal phthalate exposure and anogenital distance in male infants. (letter to the editor) Environmental Health Perspectives 2006;114 (2):A88-89.	R829436 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Swan SH, Main K, Kruse R, Stewart S, Redmon B, Ternand C, Sullivan S. Anogenital Distance and Phthalate Exposure:Swan et al Repond. (response to letter to the editor) Environmental Health Perspectives 2006;114(1):A20-A21.	R829436 (Final)	not available
Journal Article	Swan SH. Semen quality in fertile US men in relation to geographical area and pesticide exposure. International Journal of Andrology 2006;29(1):62-68.	R829436 (Final)	Abstract from PubMed
Journal Article	Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environmental Research 2008;108(2):177-184.	R829436 (Final)	Abstract from PubMed Full-text: Science Direct Exit Other: Science Direct Exit

Supplemental Keywords:

Phthalates, prenatal exposure, sexual development, play behavior, gestational age,, RFA, Scientific Discipline, Health, Health Risk Assessment, Chemistry, Epidemiology, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, genetic susceptability, Endocrine Disruptors - Human Health, childhood development, metabolites, infants, prenatal exposure, endocrine disrupting chemicals, exposure studies, sexual development, developmental effects, exposure, developmental biology, children, human growth and development, pregnant women, pregnancy, reproductive health, phthalates, epidemiologic studies

Relevant Websites:

http://www.urmc.rochester.edu/ob-gyn/research/cre/sff/index.cfm Exit

Progress and Final Reports:

Original Abstract

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.