Environ. Sci. Technol. 2010, 44, 5641–5648
Distribution and Determinants of Pesticide Mixtures in Cord Serum Using Principal Component Analysis G I L A N E T A , * ,† L Y N N R . G O L D M A N , * ,† ¨ DIN,‡ DANA BARR,‡ ANDREAS SJO 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. * Address correspondence to either author. Phone: (301) 443-8553 (G.N.); (410) 614-9301 (L.R.G.). Fax: (301) 402-0207 (G.N.); (443) 2875414 (L.R.G.). E-mail:
[email protected] (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. 10.1021/es1009778
2010 American Chemical Society
Published on Web 06/15/2010
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 environment 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 pesticides 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 organoand 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 organochlorine 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 approval 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 VOL. 44, NO. 14, 2010 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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live births delivered between November 26, 2004 and March 16, 2005 were eligible for study participation. Multiple births were excluded. Details about the study population have been published previously (16). In brief, there were 609 live births during the study period. Of these, 591 were singleton births. Cord blood was collected from 341 of these births. The primary reasons for not collecting cord blood from the remaining 250 births were (1) lack of sufficient hospital staff to extract samples during a busy time of many births in the hospital or (2) lack of feasibility because newborn was too small and umbilical cord had insufficient volume of blood for collection. Additionally, 41 samples had insufficient cord serum volume for laboratory analyses, leaving a total of 300 samples available for chemical laboratory analyses. Of these, 297 were successfully analyzed for organochlorines pesticides, and 185 (62%) were successfully analyzed for nonpersistent pesticides. Details about the cord blood collection and processing have been published previously (17, 18). In brief, cord blood samples were collected by trained hospital personnel immediately after delivery. Once extracted, samples were placed in the Labor and Delivery Suite refrigerators until transported by study personnel to a laboratory at the Johns Hopkins Bloomberg School of Public Health for processing and storage at -80 °C. Samples were collected continuously until there were 300 samples with sufficient volume of serum for chemical analysis. Frozen samples were transferred on dry ice to laboratories at the Centers for Disease Control and Prevention in Atlanta for pesticides and lipid analyses. Medical Records. Data on maternal and infant characteristics and health status were abstracted from clinical databases at the Johns Hopkins Hospital by two study personnel concurrently, using standardized forms and blinded to the environmental exposure status of the subjects. Maternal information was abstracted using the Electronic Patient Record (EPR); data from infant records were abstracted using paper files. Information collected from medical records included demographic information, maternal medical history, and infant birth outcomes. A random ten percent sample of abstracted data was verified to ensure quality control. The THREE Study contracted with Geolytics, Incorporated (East Brunswick, NJ) to obtain neighborhood demographic data at the census-block group level for each study participant. Maternal residence information from medical records was used to determine the census block group, which was then linked to block group-level demographic information, such as housing density. Addresses were discarded after geocoding was completed. Data were included in this study to examine possible risk factors associated with an increased pesticide body burden. Specifically, we examined the following maternal anthropometric and sociodemographic characteristics that might be associated with exposure to pesticide mixtures: age, race, body mass index (BMI), parity, education, health insurance, marital status, smoking, area of residence, and housing density. Age, race, education, marital status, and parity were based on self-report. The BMI was calculated based on reported prepregnancy weight and height. Insurance was categorized as private health insurance versus public assistance. Smoking was a dichotomous variable (yes/no) based on both clinical records and cotinine concentrations measured in cord serum. If clinical records indicated that the mother smoked during pregnancy, she was labeled as a smoker. Additionally, women who had cotinine cord serum levels above 10 ng/mL were categorized as smokers (1). Variables related to housing (i.e., residence within city limits, housing density) were based on block group census data. Residence within city limits was based on Federal information processing standards code 24510. Housing density was 5642
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measured as the percent of housing with multiunit structures and based on the median value for each block group. Additionally, we examined infant anthropometric characteristics including prematurity (
