Research Urinary Concentrations of Metabolites of Pyrethroid Insecticides in the General U.S. Population: National Health and Nutrition Examination Survey 1999–2002 Dana Boyd Barr, Anders O. Olsson, Lee-Yang Wong, Simeon Udunka, Samuel E. Baker, Ralph D. Whitehead Jr., Melina S. Magsumbol, Bryan L. Williams, and Larry L. Needham National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA : Pyrethroid insecticides are the most commonly used residential insecticides in the Background o Bjectivs United States. : Our objective was to assess human exposure via biomonitoring to pyrethroid insecti- cides in a representative sample of the general U.S. population ≥ 6 years of age. Methods : By using isotope-dilution high-performance liquid chromatography/electrospray chemical ionization/tandem mass spectrometry, we measured five urinary metabolites of pyrethroid insecticides in 5,046 samples collected as a part of the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Univariate, multivariate, and Pearson correlation analyses were performed using SUDAAN and SAS software, incorporating the appropriate sample weights into the analyses. Multivariate analyses included age, sex, race/ethnicity, creatinine, fasting status, and urine collection time as covariates. r esult : We detected 3-phenoxybenzoic acid (3PBA), a metabolite common to many pyrethroid insecticides, in more than 70% of the samples. hTe least-squares geometric mean (LSGM) concen - tration (corrected for covariates) of 3PBA and the frequency of detection increased from 1999–2000 (0.292 ng/mL) to 2001–2002 (0.318 ng/mL) but not significantly. Non-Hispanic blacks had significantly higher LSGM 3PBA concentrations than did non-Hispanic whites and Mexican Americans in the 2001–2002 survey period and in the combined 4-year survey periods but not in the 1999–2000 survey period. Children had significantly higher LSGM concentrations of 3PBA than did adolescents in both NHANES periods and than adults in NHANES 1999–2000. Cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid were highly correlated with each other and with 3PBA, suggesting that urinary 3PBA was derived primarily from exposure to permethrin, cypermethrin, or their degradates. c onclusi : Pyrethroid insecticide exposure in the U.S. population is widespread, and the pres- ence of its metabolites in the urine of U.S. residents indicates that children may have higher expo- sures than adolescents and adults. k ey words : general population, insecticide, NHANES, pyrethroid, 3-phenoxybenzoic acid, urine. Environ Health Perspect 118:742–748 (2010). doi:10.1289/ehp.0901275 [Online 3 February 2010] Synthetic pyrethroid insecticides are a major class of insecticides that are replacing home and some agricultural use of organophosphorus and carbamate insecticides [Agency for Toxic Substances and Disease Registry (ATSDR) 2003]. They are human-made derivatives of pyrethrins, which are naturally occurring insecticides found in a variety of plants such as chrysanthemums (ATSDR 2003). Synthetic pyrethroids are designed to be more chemi- cally potent and environmentally stable than natural pyrethrins while still retaining their rela- tively low mammalian toxicity (Soderlund et al. 2002). Although they were not used commer- cially until 1980 (Aprea et al. 1997), by 1982 pyrethroid insecticides accounted for more than 30% of the world market (Aprea et al. 1997; Leng et al. 1997a). Pyrethroid insecticides are the most widely used agents for indoor pest control (Go et al. 1999). Those developed since the early 1970s have improved photostability and minimal volatility, which have enabled their successful use in widespread agricultural applications (Laws and Hayes 1991). Although > 1,000 pyrethroids have been designed (ATSDR 2003), the U.S. Environmental 742 Protection Agency (EPA) has approved use of only about 20 pyrethroid insecticides (U.S. EPA 1991), and less than a dozen are used with any frequency in the United States. Permethrin is the most commonly used pyrethroid insecti- cide in the United States (ATSDR 2003). Like many other classes of insecticides, the pyrethroid insecticides are acute neu- rotoxicants (Aldridge 1990; Bradbury and Coats 1989; Vijverberg and van den Bercken 1990), and although dissimilar in structure and environmental and biological persis- tence to p,p´-dichlorodiphenyltrichloroethane (DDT), their modes of action are strikingly similar (Vijverberg and van den Bercken 1990; Vijverberg et al. 1982). Like DDT, pyrethroid insecticides modulate the function of voltage- gated sodium channels (Vijverberg et al. 1982); however, pyrethroid insecticides, unlike DDT, have short biological half-lives, in the order of hours, whereas DDT has a half-life of many years. Specifically, pyrethroid insecticides alter the permeability of excited nerve cells to sodium ions and cause repetitive nerve impulses that can vary between a few dozen for the less toxic non-cyano-substituted pyrethroid insecticides (type I) to up to 1,000 for the more toxic cyano- substituted pyrethroid insecticide (type II) (Aldridge 1990; Bradbury and Coats 1989; Vijverberg and van den Bercken 1990). They also have other neurobiologic actions, includ- ing effects on central γ-amino butyric acid, noradrenergic, dopaminergic, and cholinergic neurotransmission (Mandhane and Chopde 1997). In general, pyrethroid insecticides are considered among the lower-human-toxicity insecticides because mammals have higher lev- els than do insects of the enzymes that detoxify pyrethroid insecticides; thus, pyrethroid insec- ticides are rapidly metabolized and excreted in mammalian systems (Narahashi 2001). Although studies in humans demonstrate that pyrethroid insecticides are absorbed readily after exposure by inhalation, oral, and dermal routes (ATSDR 2003), the pri- mary exposure route in the general popula- tion is thought to be through dietary intake (ATSDR 2003). However, because of their burgeoning use in common household insec- ticide products such as spray insecticides, aerosol bombs, and pet shampoos (ATSDR 2003), low-level episodic exposures from household use are probable. Exposures from household use in colder areas likely occur in the spring and summer when household pests are at their peak; however, in warmer climates, pyrethroid insecticides may be used in homes year-round. Furthermore, the use of pyrethroid insecticides, particularly per- methrin, in lice treatments and shampoos Address correspondence to D.B. Barr, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Room 272, Atlanta, GA 30322 USA. Telephone: (404) 727-9605. Fax: (404) 727-8744. E-mail: dbbarr@emory.edu We thank those at the National Center for Health Statistics (NCHS) of the Centers for Disease Control (CDC) and Prevention and at Westat (Research Triangle Park, NC) who were responsible for the planning and execution of the National Health and Nutrition Examination Survey (NHANES), espe- cially B. Lewis, S. Schober, and C. Johnson. We also thank J. Pirkle, E. Gunter, and C. Pfeiffer for man- aging National Center for Environmental Health’s involvement in NHANES and for serving as liaisons with NCHS, and the Fairview University Medical Center for providing creatinine measurements. The opinions expressed in this article are those of the authors and do not necessarily reflect the official opinions of the CDC. The authors declare they have no actual or potential competing financial interests. Received 30 July 2009; accepted 3 February 2010. ovlume 118 | number 6 | June 2010 • Environmental Health Perspectives