Distribution and Determinants of Pesticide Mixtures in Cord Serum Using Principal Component Analysis GILA NETA,* ,† LYNN R. GOLDMAN,* ,† DANA BARR, ‡ ANDREAS SJ ¨ ODIN, ‡ BENJAMIN J. APELBERG, † FRANK R. WITTER, § AND ROLF U. HALDEN | Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205, Division of Environmental Health Laboratory Sciences, National Center for Environmental Health, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, Johns Hopkins School of Medicine, Baltimore, Maryland, and Arizona State University, Tempe, Arizona Received March 26, 2010. Revised manuscript received May 14, 2010. Accepted May 21, 2010. We characterized the distribution and determinants of fetal exposures to pesticide mixtures using a cross-sectional study of 297 singletons delivered at Johns Hopkins Hospital in Baltimore, MD (2004-2005). Concentrations of nine persistent and twelve nonpersistent pesticides were measured in cord serum. Mixtures were identified using principal components analysis. Associations between mixtures and maternal and infant characteristics were evaluated using multivariate analysis. p, p′ -DDE, p, p′ -DDT, trans-nonachlor, oxychlordane, bendiocarb, propoxur, and trans- and cis-permethrin were detected in 100, 90, 93, 84, 73, 55, 52, and 41% of serum samples, respectively. There were four independent pesticide components: DDT ( p, p′ - DDT + p, p′ -DDE), chlordane ( trans-nonachlor + oxychlordane), permethrin ( trans- and cis-permethrins + PBUT), and carbamate (bendiocarb + propoxur). DDT and chlordane were 6.1 (95%CI: 2.4, 15.5) and 2.1 (95%CI: 1.0, 4.2) times higher for infants of women >35, and 1.8 (95%CI: 1.2, 2.9) and 1.5 (95%CI: 1.1, 2.1) times higher in smoking mothers. DDT and carbamate were 15 (95%CI: 7, 30) and 2 (95%CI: 1, 4) times higher for infants of Asian compared with Caucasian mothers. No significant differences were observed for permethrin. Fetal exposures to pesticides are widespread, occur as mixtures, and differ by maternal race, age, and smoking status. Introduction Exposure to pesticide chemicals is widespread in the United States (1), but little is known about how these chemicals occur as mixtures in people. Sources of exposure are varied and include consumption of contaminated foods, indoor and outdoor spraying, placental transfer, and occupational pesticide uses. Most pesticides currently in use in the U.S. have biological half-lives ranging from hours to weeks (1). These nonpersistent pesticides include organophosphorus (OP), N-methyl carbamate, and pyrethroid insecticides. They are primarily used for residential and commercial insect control, as well as in agriculture (1), and often can be purchased in formulations over the counter for home and garden uses. In contrast, most persistent organochlorine pesticides, such as DDT, have been banned from use in the U.S. although they continue to be used in other countries (1). Despite being banned in the 1970s and 1980s in the U.S., organochlorine pesticides continue to persist in the environ- ment in soil and sediment, and accumulate in fatty tissues of fish and other animals (1). Because they continue to be used in other countries, exposure to organochlorine pesti- cides may also occur abroad. OP and N-methyl carbamate insecticides, both neurotoxic, are acetylcholinesterase inhibitors (1). Pyrethroid and some organochlorine insecticides interfere with ion channels in cell membranes (1). Acetylcholinesterase inhibitors inactivate acetylcholinesterase (AChE), an enzyme that hydrolyzes acetylcholine in nerve tissue, by binding to its active site and thus preventing the breakdown of acetylcholine in the central and peripheral nervous systems. Pyrethroid and some organochlorine insecticides disrupt neurological function by impeding the closing of sodium or chloride ion activation gates in nerve cells (2). Since nonpersistent insecticides have short half-lives and break down quickly, acute effects are of particular interest. However, repeated exposures to these chemicals over time may have long-term health effects including neurophysiological and neurobehavioral effects (3-5), as well as impaired fetal growth and development (4, 6-10). Early life exposures to pesticides may be a period of particular vulnerability because of increased permeability of the blood-brain barrier, potential impairment of organo- and neurogenesis in utero, and higher exposure levels given their body size and composition (11). Thus, identification of in utero exposures to these classes of pesticides is of particular interest. Human biomonitoring studies have found detectable levels of OP, N-methyl carbamate, pyrethroid, and orga- nochlorine pesticide metabolites in urine or blood samples collected from children and adults (1, 12). Few studies have been carried out in the U.S. evaluating exposures in utero (13-15), and little is known about how these exposures occur as mixtures. Measurement of levels in cord serum as opposed to maternal serum is a more direct estimate of exposure to the fetus. The aims of the current study were to identify mixtures of cord serum concentrations of OP, carbamate, pyrethroid, and organochlorine pesticides using principal component analysis, and to identify demographic and socioeconomic factors associated with in utero mixtures among a population of babies born in Baltimore, MD from November 2004 to March 2005. Material and Methods Subjects. We conducted a cross-sectional study of newborn deliveries at the Johns Hopkins Hospital Labor and Delivery Suite in Baltimore. The Baltimore Tracking Health Related to Environmental Exposures (THREE) Study received ap- proval from the Johns Hopkins Medicine Institutional Review Board. All study specimens collected would have otherwise been discarded. Medical records utilized for data collection were available to hospital and study personnel. Because all specimens and data collected from medical records were made anonymous, informed consent was not required and the study was determined to be HIPAA exempt. All singleton * Address correspondence to either author. Phone: (301) 443-8553 (G.N.); (410) 614-9301 (L.R.G.). Fax: (301) 402-0207 (G.N.); (443) 287- 5414 (L.R.G.). E-mail: netagil@mail.nih.gov (G.N.); lgoldman@ jhsph.edu (L.R.G.). † Johns Hopkins Bloomberg School of Public Health. ‡ U.S. Centers for Disease Control and Prevention. § Johns Hopkins School of Medicine. | Arizona State University. Environ. Sci. Technol. 2010, 44, 5641–5648 10.1021/es1009778  2010 American Chemical Society VOL. 44, NO. 14, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 5641 Published on Web 06/15/2010