Pyrethroid metabolites in the U.S. population a continuous survey, fielded on an ongoing basis. Each year of data collection is based on a representative sample, which covers all ages of the civilian noninstitutionalized popula- tion. Public-use data files have been released in 2-year groupings (cycles). In this study, national population estimates for pyrethroid metabolites and estimates for the three largest race/ethnicity subgroups in the U.S. popula- tion (non-Hispanic white, non-Hispanic black, and Mexican American) are derived from two 2-year cycles of the survey, NHANES Glucuronide conjugates 3-phenoxybenzoic acid Figure 1. General metabolism of both type I and type II pyrethroid insecticides. Type I insecticides have an R2 substitution of H, and type II insecticides have an R2 substitution of CN (cyano group). Table 1. Common pyrethroid insecticides and their corresponding urinary metabolites. R1 = CI, Br, CH3 R2 = H, CN R3, = H, F R1 R1 O Chrysanthemic acid metabolite OH R1 R1 Further oxidative metabolism for CH3 substituted Pyrethroid insecticide 3PBA Permethrin Cypermethrin Cyfluthrin Deltamethrin Allethrin Resmethrin Fenvalerate OH O X X X X X X O cis-DCCA X X X O O R2 may allow for direct exposure to certain pyre- throid insecticides in children. Mammalian animal studies have identified several important metabolites of pyrethroid insecticides. 3-Phenoxybenzoic acid (3PBA) is a metabolite of many pyrethroid insecticides resulting from the oxidation of the hydro- lytic product of many pyrethroid insecticides, 3-phenoxybenzyl alcohol (Figure 1, Table 1). Similarly, 4-fluoro-3-phenoxybenzoic acid (4F3PBA) is a metabolite of the fluorine- substituted pyrethroid insecticide cyfluthrin. Chrysanthemic acid derivatives are also obtained after pyrethroid insecticide metabolism (Figure 1). Cis- and trans-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropane-1-carboxylic acid (cis- and trans-DCCA) are metabolites of the chlorinated pyrethroid insecticides permethrin, cypermethrin, and cyfluthrin. Cis-(2,2- dibromovinyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (cis-DBCA) is a selective metabolite of deltamethrin. Human dosing studies of cypermethrin isomers (Eadsforth and Baldwin 1983; Eadsforth et al. 1988; Woollen et al. 1992) and cyfluthrin (Leng et al. 1997b) and occupational exposure studies (Aprea et al. 1997; Hardt and Angerer 2003; Leng et al. 1996) have confirmed that many of these metabolites are important markers of pyrethroid insecticide exposure in humans (Leng et al. 1997b). The presence of metabolites represent- ing both halves of the pyrethroid insecticide molecule can indicate the source pyrethroid insecticides for the metabolites. We report urinary concentrations of five metabolites of pyrethroid insecticides in 1,998 persons of the general U.S. population 6–59 years of age in 1999 and 2000 and in 3,048 persons ≥ 6 years of age in 2001 and 2002. Specifically, we report urinary concentra- tions of 3PBA, a common metabolite of up to 18 synthetic pyrethroid insecticides; 4F3PBA, a metabolite of cyfluthrin; cis-DCCA and trans-DCCA, geometric isomeric metabolites of permethrin, cypermethrin, and cyfluthrin; and cis-DBCA, a metabolite of deltamethrin (Figure 2). The data we report are representa- tive of the civilian, noninstitutionalized U.S. population and are stratified by age, sex, and race/ethnicity. We also evaluated fasting dura- tion and time of sample collection (i.e., morn- ing, afternoon, evening) to see if the metabolite concentrations may have been influenced by these factors. Methods Study population. The National Health and Nutrition Examination Survey (NHANES), conducted by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), is designed to measure the health and nutrition status of the civilian noninstitutionalized U.S. population (CDC 2003). In 1999, NHANES became Environmental Health Perspectives • volume 118 | number 6 | June 2010 R3 O R3 O HO O 3-phenoxybenzyl alcohol 4F3PBA X F O HO R2 Metabolite trans-DCCA X X X OH O R3 O cis-DBCA X Some metabolites are excreted as glucuronide conjugates, which we liberated before analysis; only the liberated metabolites are listed here. 3-phenoxybenzoic acid (3PBA) 4-ﬂuoro-3-phenoxybenzoic acid (4F3PBA) CI CI cis-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropane- 1-carboxylic acid (cis-DCCA) O OH CI CI trans-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropane- 1-carboxylic acid (trans-DCCA) O OH Figure 2. Pyrethroid metabolites measured in NHANES 1999–2002. Br Br cis-(2,2-dibromovinyl)- 2,2-dimethylcyclopropane- 1-carboxylic acid (cis-DB CA) O OH 743