Toxicology and Applied Pharmacology 206 (2005) 246–254 www.elsevier.com/locate/ytaap Biomarkers in assessing residential insecticide exposures during pregnancy and effects on fetal growth R.M. Whyatta,T, D. Camannc, F.P. Pereraa, V.A. Rauha, D Tanga, P.L. Kinneya, R Garfinke1a, H. Andrewsa, L. Hoepnera, D.B. Barrb aColumbia Center for Children’s Environmental Health, Department of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, 60 Haven Avenue, B-1, New York, NY 10032, USA bNational Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA cSouthwest Research Institute, San Antonio, TX 78228-0510, USA Received 1 July 2004; accepted 17 November 2004 Available online 25 April 2005 Abstract The Columbia Center for Children’s Environmental Health is using a combination of environmental and biologic measures to evaluate the effects of prenatal insecticide exposures among urban minorities in New York City. Of the 571 women enrolled, 85% report using some form of pest control during pregnancy and 46% report using exterminators, can sprays, and/or pest bombs. Chlorpyrifos, diazinon, and propoxur were detected in 99.7–100% of 48-h personal air samples collected from the mothers during pregnancy (n = 394) and in 39–70% of blood samples collected from the mothers (n = 326) and/or newborns (n = 341) at delivery. Maternal and newborn blood levels are similar and highly correlated (r = 0.4–08, P b 0.001). Levels of insecticides in blood samples and/or personal air samples decreased significantly following the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of chlorpyrifos and diazinon. Among infants born prior to 1/1/01, birth weight decreased by 67.3 g (95% confidence interval (CI) À116.6 to À17.8, P = 0.008) and birth length decreased by 0.43 centimeters (95% CI, À0.73 to À0.14, P = 0.004) for each unit increase in log-transformed cord plasma chlorpyrifos levels. Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (P V 0.007). Birth weight averaged 215.1 g less (95% CI À384.7 to À45.5) among those with the highest exposures compared to those without detectable levels. No association was seen between birth weight and length and cord plasma chlorpyrifos or diazinon among newborns born after 1/1/01 (P N 0.8). Results support recent regulatory action to phase out residential uses of these insecticides. D 2005 Elsevier Inc. All rights reserved. Keywords: Insecticides; Prenatal; Residential; Minority; Urban; Women; Birth weight; Birth length Introduction use appears to be particularly high among minority populations residing in New York City (Berkowitz et al., Residential pesticide use is widespread in the United 2003; Surgan et al., 2002; Thier et al., 1998; Whyatt et al., States, with approximately 80–90% of American house- 2002, 2003). A 1997 study of pesticide use in New York holds using pesticides (Landrigan et al., 1999). Insecticide State found that the heaviest application (in gallons and pounds) of legally registered pesticides by licensed appli- cators occurred not in the agricultural counties but in the Abbreviations: LPM, liters per minute; PUF, polyurethane foam; QC, boroughs of Manhattan and Brooklyn in New York City quality control; EPA, U.S. Environmental Protection Agency; CDC, (Thier et al., 1998). Chlorpyrifos was one of the insecticides Centers for Disease Control and Prevention; cm, centimeter; kg, kilogram; pg/g, picogram/gram; CI, confidence interval. most heavily applied in New York City including by pest T Corresponding author. Fax: +1 646 459 9610. control operators for the New York City Housing Authority E-mail address: [email protected] (R.M. Whyatt). (Landrigan et al., 1999; Thier et al., 1998). Other 0041-008X/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.taap.2004.11.027 R.M. Whyatt et al. / Toxicology and Applied Pharmacology 206 (2005) 246–254 247 insecticides commonly used in the home included the cigarettes or used other tobacco products during pregnancy, organophosphate diazinon and the carbamate propoxur used illicit drugs, had diabetes, hypertension, or known and bendiocarb (Landrigan et al., 1999; Whitmore et al., HIV, or had their first prenatal visit after the 20th week of 1994; Whyatt et al., 2002, 2003). However, use of pregnancy. The study was approved by the Institutional chlorpyrifos and diazinon appears to have decreased Review Board of Columbia University and informed substantially as a result of the 2000–2001 regulatory actions consent was obtained from all study subjects. The 571 by the U.S. Environmental Protection Agency (EPA) to subjects included in the current report were enrolled phase out their residential uses (Carlton et al., 2004; U.S. between January 1998 and January 2004. Environmental Protection Agency, 2000a, 2001a; Whyatt et al., 2003, 2004). While human data on effects of residential Questionnaire data. A 45-min questionnaire, administered pesticide exposure during pregnancy are limited, exper- to each woman in her home by a trained bilingual imental data in laboratory animals suggest that exposures to interviewer during the 3rd trimester of pregnancy, collects certain organophosphates (including chlorpyrifos and dia- information on demographics, home characteristics, lifetime zinon) during pregnancy or early life can impair fetal growth residential history, history of active and passive smoking, and neurocognitive development in the offspring (reviewed occupational history, maternal education and income level, in Eskenazi et al., 1999). Reduction in birth weight was also alcohol and drug use during pregnancy, and history of seen experimentally in a two-generation reproductive study residential pesticide use. Information about pesticide use of propoxur in rats, but only at high exposure levels (U.S. includes whether or not any pest control measures were used Environmental Protection Agency, 1997). However, con- by an exterminator or by others (the woman herself, other trary to results presented here, two recent epidemiologic household members, or the building superintendent) during studies failed to find associations between prenatal chlor- pregnancy and if so what types of measures were used pyrifos exposure and either birth weight or birth length (Perera et al., 2003; Whyatt et al., 2002, 2003, 2004). (Berkowitz et al., 2004; Eskenazi et al., 2004). Both studies used levels of the chemical-specific metabolite of chlorpyr- Prenatal personal ambient air samples. As described in ifos (3,5,6-trichloro-2-pyridinol (TCPY)) in urine samples detail previously (Perera et al., 2003; Whyatt et al., 2002, collected from the mother during pregnancy as the 2003, 2004), women in the cohort are asked to wear a small dosimeter of prenatal exposure. The Columbia Center for backpack during the 3rd trimester of pregnancy containing a Children’s Environmental Health is conducting a large-scale personal ambient air monitor during the daytime hours for prospective cohort study using a combination of environ- two consecutive days and to place the monitor near the bed at mental and biologic monitoring to evaluate the effects of night. The personal air sampling pumps operated continu- prenatal insecticide exposure on fetal growth and infant ously at 4 liters per minute (LPM) over this period, collecting neurocognitive development. Enrollment began in 1998 and particles of V2.5 Am in diameter on a precleaned quartz will be completed by 2006 with a total of 730 mother/ microfiber filter and collecting semivolatile vapors and newborn pairs enrolled; 571 pairs have been enrolled to aerosols on a polyurethane foam (PUF) cartridge back-up. date. Prior results on the research have been published Analyses for pesticide levels are carried out at Southwest (Perera et al., 2003; Whyatt et al., 2002, 2003, 2004). The Research Institute as described (Perera et al., 2003; Whyatt et current manuscript updates these research findings to al., 2002, 2003, 2004). The pesticides being measured are the include a larger sample size and summarizes research results organophosphates chlorpyrifos, diazinon, malathion, and to date. methyl parathion, the carbamates propoxur, bendiocarb, carbofuran, and carbaryl, and the pyrethorids cis- and trans- permethrin. To date, air samples have been analyzed for 394 Methods women in the cohort. The personal air monitorings for these women took place between 1998 and 2002. Study subjects. Study protocols, including eligibility requirements as well as the comparability between those Blood samples. A sample of umbilical cord blood is who agreed to participate compared to those who refused, collected as close to delivery as possible by syringing the have been described in detail previously (Perera et al., blood into a heparinized syringe to avoid clotting. A sample 2003; Whyatt et al., 2002, 2003). Bilingual research of maternal blood is obtained within 2 days postpartum into workers attend the prenatal clinics at Harlem and New heparinized vacutainer tubes by the hospital staff. Blood York Presbyterian hospitals to explain the study and processing and analysis have been described in detail determine eligibility if a woman is interested in participat- previously (Perera et al., 2003; Whyatt et al., 2002, 2003, ing. The study is restricted to women 18–35 years old who 2004). Analyses are undertaken at the Centers for Disease self-identified as African American or Dominican and had Control and Prevention (Whyatt et al., 2003). Methods for resided in Northern Manhattan (Central Harlem or Wash- the laboratory assay, including quality control, reproduci- ington Heights/Inwood) or the South Bronx for z1 year bility, and limits of detection, have been published (Barr prior to pregnancy. Women are excluded if they smoked et al., 2002). Twenty-nine pesticides are being measured 248 R.M. Whyatt et al. / Toxicology and Applied Pharmacology 206 (2005) 246–254 in blood as described (Whyatt et al., 2003) and include (from the mother and/or newborn) had been obtained at the same insecticides that are being measured in air.