Research Exposure of the U.S. Population to Acrylamide in the National Health and Nutrition Examination Survey 2003–2004 Hubert W. Vesper, Samuel P. Caudill, John D. Osterloh, Tunde Meyers, Deanna Scott, and Gary L. Myers Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Background : The lifelong exposure of the population to acrylamide has raised concerns about the possible health effects of the chemical. Data on the extent of exposure to acrylamide and its primary metabolite, glycidamide, are needed to aid in the assessment of potential health effects. o Bjectivs : The aim of this study was to assess human exposure to acrylamide and glycidamide in the general U.S. population through the measurement of hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA). Methods : HbAA and HbGA were measured in 7,166 subjects from the National Health and Nutrition Examination Survey. Stratified HbAA and HbGA data were reported by sex, age groups, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white), and smoking status based on serum cotinine levels. Covariate-adjusted geometric means for each demographic group were calculated using multiple regression analysis. r esult : HbAA and HbGA levels ranged from 3 to 910 and from 4 to 756 pmol/g hemoglobin, respectively, with smokers having the highest levels overall. Tobacco smoke exposure in nonsmokers had a small but significant effect on HbAA and HbGA levels. Adjusted geometric mean levels for children 3–11 years of age were higher than for adults ≥ 60 years of age [mean (95% confidence interval): HbAA, 54.5 (49.1–51.5) and HbGA, 73.9 (71.3–76.6) vs. HbAA, 46.2 (44.3–48.2) and HbGA, 41.8 (38.7–45.2)]. Levels were highest in Mexican Americans [HbAA: 54.8 (51.9–57.8), HbGA: 57.9 (53.7–62.5)], whereas non-Hispanic blacks had the lowest HbGA levels [43.5 (41.1–45.9)]. c onclusi : U.S. population levels of acrylamide and glycidamide adducts are described. The high variability among individuals but modest differences between population subgroups suggest that sex, age, and race/ethnicity do not strongly affect acrylamide exposure. Adduct concentration data can be used to estimate relative exposure and to validate intake estimates. Key words : acrylamide, biomonitoring, glycidamide, human exposure, hemoglobin adducts, NHANES, U.S. population. Environ Health Perspect 118:278–283 (2010). doi:10.1289/ ehp.0901021 available via http://dx.doi.org/ [Online 14 October 2009] dose­dependent manner as shown in animal and human studies (Fennell et al. 2005; Tareke et al. 2006), with occupational expo­ sures (Jones et al. 2006; Schettgen et al. 2004), with tobacco use (Kütting et al. 2008; Scherer et al. 2007; Schettgen et al. 2004; Vesper et al. 2008), and with food con­ sumption (Hagmar et al. 2005; Wilson et al. 2008). The use of these hemoglobin adducts for exposure assessments is analogous to the use of glycated hemoglobin to monitor blood glucose levels in diabetic patients (Osterman­ Golkar and Vesper 2006). HbAA and HbGA are stable over the life span of the erythro­ cytes, and they therefore offer a measure of cumulative internal exposure over a period of 120 days (Fennell et al. 1992). To date, no data on internal acrylamide and glycidamide exposure acquired by use of HbAA and HbGA in the general U.S. popu­ lation are available to aid in the assessment of health risks associated with this exposure. The aim of this study was to determine human exposure to acrylamide and its primary metabolite glycidamide in a representative subset of the general U.S. population. Materials and Methods Specimens were obtained from participants of the 2003–2004 cycle of the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of the noninstitutionalized civilian population of the United States. NHANES obtained a stratified, multistage probability Address correspondence to H.W. Vesper, 4770 Buford Hwy NE, MS F25, Atlanta, GA 30341 USA. Telephone: (770) 488­ 4191. Fax: (770) 488­ 7030. E­mail: HVesper@cdc.gov Supplemental Material is available online (doi:10.1289/ehp.0901021.S1 via http://dx.doi.org/). We thank D. Doerge for characterizing our stan­ dards, A. Smith, K. Dobbins, and L. Ingham for their technical support, and those individuals from the National Center for Health Statistics/CDC who par­ ticipated in the planning and implementation of the National Health and Nutrition Examination Survey. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Agency for Toxic Substances and Disease Registry, the Public Health Service, or the U.S. Department of Health and Human Services. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention or the Agency for Toxic Substances and Disease Registry. The authors declare they have no competing financial interests. Received 26 May 2009; accepted 14 October 2009. ovlume 118 | number 2 | February 2010 • Environmental Health Perspectives Acrylamide is an environmental and industrial chemical. People are exposed to this chemical through its formation in foods during heat­ ing (Dybing et al. 2005; Mottram et al. 2002; Stadler et al. 2002), tobacco smoke (Smith et al. 2000), and occupational activities involving the production and use of acrylamide (Hagmar et al. 2005; Jones et al. 2006; Paulsson et al. 2006). The health effects of acrylamide have been reviewed extensively in the literature (Exon 2006; Klaunig 2008; LoPachin et al. 2008; Shipp et al. 2006). Acrylamide can be neurotoxic in humans and animals and carci­ nogenic in animals, and has been categorized as a suspected human carcinogen [Hagmar et al. 2001; International Agency for Research on Cancer (IARC) 1995; Manjanatha et al. 2006]. It is also a reproductive and develop­ mental toxicant in male rats and mice [National Toxicology Program (NTP) 2004]. The lifelong exposure of most of the population to acrylam­ ide through food and smoking has raised con­ cerns about its potential health effects at these low levels of intake. To aid in the assessment of possible health risks, the extent of the actual acrylamide exposure in the general population needs to be characterized. Acrylamide is metabolized to glycid­ amide by cytochrome P450 2E1 (CYP2E1). 278 Glycidamide forms DNA adducts (Gamboa da Costa et al. 2003) and is assumed to be the agent responsible for causing the toxicologicl effects. Recent studies using CYP2E1 knock­ out mice have confirmed glycidamide as the actual genotoxic and reproductive toxic agent (Ghanayem et al. 2005a, 2005b). CYP2E1 is regulated at the transcriptional, transla­ tional, and posttranslational level (Ingelman­ Sundberg et al. 1994) and affected by genetic polymorphisms (Itoga et al. 2002; McCarver et al. 1998). The glycidamide­to­acrylamide ratio, which can be used as an indicator of the extent of acrylamide metabolism by CYP2E1, was found to be highly variable between indi­ viduals (Bjellaas et al. 2007; Hartmann et al. 2008 Schettgen et al. 2004; Vesper et al. 2007, 2008), indicating that interindividual differences may be a factor in susceptibility to toxic effects. This high variability makes the prediction of glycidamide exposure based on acrylamide exposure difficult, and it creates the need for measuring glycidamide exposure as well as acrylamide exposure. Hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) are well­ established biomarkers of exposure to these chemicals (Dybing et al. 2005; Ogawa et al. 2006). The adducts are formed in a