covariatea­djusted geometric HbGA levels were higher in females [108 (95% CI, 99.4–117)] than in males [87.9 (95% CI, 78.5–98.5)], whereas no difference was observed for HbAA levels. HbGA:HbAA ratios were higher in females than males across all percentiles of coti­ nine [1.59 (95% CI, 1.28–1.97) in women; 0.87 (95% CI, 0.74–1.03) in men, at the 90th percentile of cotinine each]. In addition, HbAA, HbGA levels, and the HbGA:HbAA ratios decreased with increasing age, except for Mexican Americans, where HbAA and HbGA levels remained constant. NonH­ispanic blacks had the lowest HbGA values at age groups 40 years [83.4 (95% CI, 74.8–93.1) pmol/g hemoglobin] and 60 years [59.1 (95% CI, 51.1–68.5) pmol/g hemoglobin] and the low­ est HbAA/HbGA ratios across all age groups [0.45 (95% CI, 0.36–0.56) at age 60]. In contrast to nonsmokers, the HbGA:HbAA ratios decreased with increasing cotinine levels. HbAA levels modestly increased with increas­ ing BSA in both females and males. An increase in serum cotinine was associ­ ated with an increase in HbAA. This increase was highest at low BSA levels. A 10% increase in serum cotinine levels was associated with an increase in HbAA by 3.16% (95% CI, 2.52–3.80), 2.47% (95% CI, 1.95–2.99) and 1.93% (95% CI, 1.37–2.49) at the 25th, 50th, and 75th percentile of BSA, respectively. For HbGA, the estimated slope for the effect of the logarithm of cotinine levels was 0.1476 (p = 0.0001), indicating that every 10% increase in serum cotinine was associated with a 1.41% (95% CI, 0.89–1.95) increase in HbGA. A 10% increase in serum cotinine was associated with a decrease in the HbGA:HbAA ratio of 1.1% (95% CI, –1.44 to 0.76) in women and a nonsignificant decrease of 0.25% (95% CI, –0.54 to 0.005) in men. Relationship between HbAA and HbGA. The logt­ransformed HbAA and HbGA levels were linearly related (r2 = 0.4213, p < 0.0001). A multiple regression model for nonsmok­ ers that included sex, race/ethnicity, cotinine, and BSA as independent variables to predict HbGA levels based on HbAA levels showed a significant interaction between race/ethnicity and HbAA levels (p = 0.0133). In this model, a 10% increase in HbAA was accompanied by a 9.62% (95% CI, 8.92–10.35%), 7.55% (95% CI, 6.21–8.88%), and 9.65% (95% CI, 7.96– 11.36%) increase in HbGA for nonH­ispanic whites, non­Hispanic blacks , and Mexican Americans, respectively. In a similar model for smokers, a 10% increase in HbAA was accom­ panied by an 8.62% increase in HbGA (no interactions between HbAA and the other vari­ ables were detected). Discussion Exposure to acrylamide, as indicated by the presence of HbAA or HbGA, was detectable Exposure of the U.S. population to acrylamide in > 99% of all NHANES participants, indi­ cating that most of the U.S. population is exposed to this chemical. However, the levels of HbAA or HbGA were not profoundly dif­ ferent among several population subgroups but differed highly among individuals, sug­ gesting that individual exposures were affected mainly by factors other than age, sex, or race/ ethnicity. In addition, the relationship of levels of HbAA to HbGA could be useful in study­ ing factors related to the metabolic conversion of acrylamide to the more toxic glycidamide. The HbAA levels in children were mod­ estly higher than those in two older age groups, and the HbGA levels in children were higher than those in all four older age groups even after adjustment for body size, cotinine, and sex. The higher levels in chil­ dren may be due to the known larger intake of food per body mass in children, particularly acrylamider­ich foods such as french fries and potato chips, as suggested elsewhere (Dybing et al. 2005; Mucci and Wilson 2008). In addi­ tion, children have the highest HbGA:HbAA ratios, whereas adults ≥ 60 years of age have the lowest ratios. Smokers show similar pat­ terns, with biomarker values and ratios being higher at young age. This suggests differences in the acrylamide metabolism or metabolic rate in these age groups. The reasons for these different ratios are not fully understood. Metabolism and clearance of drugs are higher in children in part because of the larger liver­ to­body weight ratio and the higher blood flow through the liver compared with older adults, in whom liver volume and liver blood flow are decreased (Greim and Snyder 2008). Further investigation is needed to assess pos­ sible health effects associated with acrylamide exposure in children. The observed differences in acrylam­ ide exposure between race/ethnic groups, with Mexican Americans having the highest HbAA and HbGA levels and non­Hispanic blacks having the lowest HbGA levels and HbGA:HbAA ratios in nonsmokers and smokers, have not been described before. The differences observed in nonsmokers could be explained by different food consumption patterns. The 2003–2004 U.S. Department of Agriculture (USDA) food consumption survey reported differences in food con­ sumption patterns for total sugars and car­ bohydrate­rich food among non­Hispanic whites, non­ Hispanic blacks, and Mexican Americans (USDAA­RS 2007), and this pat ­ tern appears similar to the pattern observed for HbAA and HbGA. Carbohydrates are precursors for acrylamide formation during food processing (Mottram et al. 2002; Stadler et al. 2002). Thus, elevated consumption of carbohydrater­ich food in Mexican Americans may explain in part the elevated HbAA and HbGA levels in this group. The significantly lower HbGA:HbAA ratios and HbGA forma­ tion rate (per unit increase of HbAA) in non­ Hispanic blacks may indicate differences in polymorphisms of the genes for CYP2E1 or of the genes for glutathione St­ransferase (GST), which are involved in phase II detoxification of acrylamide and glycidamide. Different fre­ quencies in polymorphisms in the genes for CYP2E1 in different race/ethnicity groups have been mentioned in literature (Bartsch et al. 2000; Bolt et al. 2003), and associations between polymorphisms in the genes for GST and the HbGA:HbAA ratio have been reported (Duale et al. 2009). Medications and alcohol are also metabolized by CYP2E1 and thus may affect CYP2E1 activity and metabolism of acrylamide to glycidamide. These factors could not be assessed in this study. Therefore, further studies are needed to better explain these differ­ ences in the observed HbGA:HbAA ratio. The ranges of HbAA and HbGA levels measured in this study are similar to those Table 2. Covariate-adjusted geometric mean estimates (95% CI) of HbAA, HbGA (pmol/g hemoglobin), and the HbGA:HbAA ratio in the nonsmoking U.S. population by sex, age, and race/ethnicity. Parameter Sex Age group Race/ethnicity Group Male Female 3–11 12–19 20–39 40–59 ≥ 60 NHW NHB MA HbAA 51.7 (49.6–53.8) 50.3 (49.1–51.5) 54.5 (52.4–56.8)c 51.8 (49.9–53.7) 52.8 (50.5–55.3) 50.7 (47.9–53.6) 46.2 (44.3–48.2)e 50.7 (49.1–52.3) 48.9 (46.14–51.84) 54.8 (51.9–57.8)h HbGA 50.1 (50.7–56.3) 53.4 (48.2–52.1)b 73.9 (71.3–76.6)d 51.9 (48.3–55.7) 52.7 (48.8–56.8) 50.0 (47.8–52.4) 41.8 (38.7–45.2)d 52.6 (50.3–54.9)f 43.5 (41.1–45.9)g 57.9 (53.7–62.5) HbGA:HbAA ratioa 0.97 (0.94–1.02) 1.07 (1.03–1.13) 1.62 (1.39–1.87) 1.42 (1.29–1.58) 1.16 (1.12–1.20) 0.86 (0.78–0.94) 0.63 (0.51–0.78) 1.03 (0.98–1.07) 0.90 (0.82–1.00) 1.06 (0.99–1.13) Abbreviations: MA, Mexican American; NHB, non-Hispanic black; NHW, non-Hispanic white. Variables used in the model: age group, sex, race/ethnicity log-converted cotinine levels, and BSA (except for the HbGA model). aBecause of significant race/ethnicity–cotinine and sex–BSA interactions, only the levels obtained at the 50th per- centile of cotinine (for race/ethnicity levels) and of BSA (for sex levels) are shown. Similarly, for age groups, the levels at the median age for each age group (7 years for 3- to 11-year group, 15.5 years for 12- to 19-year group, 29.5 years for 20- to 39-year group, 49.5 years for 40- to 49-year group, 70 years for ≥ 60-year group) are shown. bDifferent from males (p < 0.004). cDifferent from 12- to 19-year group (p = 0.04), 40- to 59-year group (p = 0.03). dDifferent from all age groups (p < 0.0001). eDifferent from 3- to 11-year group, 12- to 19-year group, 20- to 39-year group, 40- to 59-year group (p < 0.0001 for all groups). fDifferent from MA (p = 0.004), NHB (p < 0.0001). gDifferent from MA (p < 0.0001). hDifferent from NHW (p < 0.008), NHB (p < 0.0001). Environmental Health Perspectives • volume 118 | number 2 | February 2010 281