Elliott et al. detection. As expected, acetone was present in much higher concentrations than other VOCs because it is produced endogenously. Men had signiﬁcantly higher measured values for most VOCs (Wilcoxon rank-sum tests, p < 0.05), except for 1,1,1-TCE, 1,4-DCB, and tetrachloroethene (TCE). As has been reported previously for this population (Churchill et al. 2001), Mexican Americans had lower concentrations of benzene, ethyl- benzene, styrene, TCE, and toluene and sig- niﬁcantly higher levels of m,p-xylene than did other ethnic groups. For 1,4-DCB, non- Hispanic whites had the lowest and African Americans the highest concentrations. In the models unadjusted for smoking, reductions in at least one pulmonary function outcome were statistically significant for 1,4-DCB, benzene, ethylbenzene, styrene, and toluene (data not shown). However, when these models were adjusted for smoking vari- ables, only 1,4-DCB remained statistically sig- niﬁcantly associated with reduced pulmonary function. For example, after adjustment for smoking, VOC β-coefﬁcients for FEV1 changed from –72 mL (p < 0.0001) to –1 mL (p = 0.95) for benzene, from –51 mL (p = 0.03) to 15 mL (p = 0.57) for ethylbenzene, from –61 mL (p = 0.01) to 42 mL (p = 0.19) for styrene, and from –69 mL (p < 0.01) to 16 mL (p = 0.60) for toluene, whereas the β-coefﬁcient for 1,4-DCB remained unchanged (–24 mL, p = 0.04). Because only 1,4-DCB maintained its association with pulmonary function in the presence of smoking, further analyses were limited to this VOC. The exposure distribu- tion of 1,4-DCB differed by race/ethnicity group (Kruskal-Wallis test, p < 0.0001), with African Americans having the highest expo- sures (Table 3). Among all participants, 1,4-DCB was inversely related to all four pulmonary function measures but was statistically signiﬁcant only for FEV1 and MMEFR (Table 4). Power is limited for sex-specific analyses; however, higher 1,4-DCB was related to lower levels of each pulmonary function measure in both men and women. Likewise, 1,4-DCB was inversely associated with all four measures within each of the race groupings, although numbers become unstable. Numbers are further reduced within the six race/sex groups, but 1,4-DCB was inversely related to at least one of the four pul- monary function measures in each of the six subgroups. The results were strongest and sta- tistically significant for non-Hispanic white females (FEV1, β = –266, p = 0.02) and African-American males (FEV1, β = –282, p = 0.01), although we did not ﬁnd signiﬁcant evi- dence of effect modiﬁcation by race/sex combi- nations (multiple partial F-test, p > 0.10 for all pulmonary function outcomes). Higher levels of 1,4-DCB were related to reduced pulmonary function in never-smokers as well as smokers (Table 4). Results for never-smokers were similar when we deﬁned nonsmokers in a more stringent manner as having serum cotinine < 0.62 ng/mL, the 75th percentile among nonsmokers (n = 299; data not shown). To further examine the relationship between 1,4-DCB and pulmonary function, we conducted additional analyses using uri- nary concentrations of 2,5-dichlorophenol Table 3. Distribution of 1,4-DCB by sex and race/ethnicity group in NHANES III Priority Toxicant Reference Range Study, 1988–1994. No. Median 200 0.22 157 0.56 122 0.34 Males Range 0.05–16.98 0.09–51.24 0.05–51.89 10th 0.09 0.15 0.10 90th 1.75 6.56 5.64 No. Median 140 0.20 111 0.52 98 0.29 Females Range 0.05–20.47 0.08–46.46 0.05–26.52 10th 0.08 0.16 0.09 90th 1.66 8.67 7.26 Table 4. Linear regression coefﬁcients [β (95% CI)] for 1,4-DCBa and pulmonary function outcomes in NHANES III, 1988–1994. Non-Hispanic Whites African Americans Mexican Americans 10th and 90th are percentiles. All participantsb Males Females Whites African Americans Mexican Americans White males White females African-American males African-American females Mexican-American males Mexican-American females Ever smokers Never smokers 1212 No. 846 488 358 334 266 219 198 137 156 110 122 197 458 388 FEV1 –96 (–182 to –11)* –103 (–227 to 21) –82 (–191 to 27) –155 (–320 to 9) –153 (–300 to –6)* –46 (–183 to 90) –26 (–260 to 208) –266 (–488 to –43)* –282 (–497 to –66)* 43 (–152 to 239) –68 (–289 to 152) –95 (–264 to 74) –137 (–259 to –16)* –57 (–177 to 64) FVC –64 (–162 to 33) –76 (–218 to 65) –46 (–170 to 78) –112 (–303 to 79) – 99 (–262 to 64) –53 (–214 to 108) 69 (–204 to 343) –259 (–512 to –7)* –242 (–481 to –3)* 113 (–106 to 332) –85 (–342 to 172) –64 (–274 to 146) –113 (–250 to 25) –18 (–157 to 122) (2,5-DCP), the major metabolite of 1,4-DCB (Hissink et al. 1997). 2,5-DCP was one of 12 pesticide metabolites measured in the urine of NHANES III participants, using capillary gas chromatography and tandem mass spectrome- try (Hill et al. 1995b). Although 2,5-DCP measurements were available only on 534 of the 846 subjects included in the analysis of 1,4- DCB, the β-coefﬁcients for both compounds were inversely related to all pulmonary function measures, and the result for FEV1 was more sta- tistically precise. For example, the expected change in FEV1 with each increase in exposure from the 10th to 90th percentile (3.76 µg/L for 1,4-DCB and 4.67 µg/L for 2,5-DCP) was –96 mL (p = 0.03) for 1,4-DCB and –134 mL (p = 0.02) for 2,5-DCP. To facilitate interpretation of the associa- tion between 1,4-DCB and pulmonary func- tion that we observed in these data using logarithmic transformation, we categorized nontransformed values of 1,4-DCB into deciles. Figure 1 shows the changes in FEV1 (milliliters) and MMEFR (milliliters per sec- ond) for each decile of 1,4-DCB exposure, compared with participants in the lowest decile. Tests for linear trend across deciles were statistically signiﬁcant (FEV1, p = 0.02; MMEFR, p = 0.02). Subjects in the highest decile of exposure had FEV1 decrements of –153 mL [95% confidence interval (CI), –297 to –8] and MMEFR decrements of –346 mL/sec (95% CI, –667 to –24), com- pared with participants in the lowest decile. Discussion We examined the relationship between blood concentrations of 11 VOCs with median val- ues above the limit of detection and pul- monary function outcomes in participants of NHANES III and found that 1,4-DCB was the only VOC associated with reduced pul- monary function after adjustment for smoking. Participants in the highest decile of 1,4-DCB concentration had FEV1 and MMEFR decre- ments of –153 mL (95% CI, –297 to –8) and PEFR –207 (–472 to 58) –183 (–575 to 209) –211 (–542 to 121) –181 (–665 to 301) –517 (–1,016 to –18)* 65 (–345 to 474) –154 (–849 to 540) –202 (–855 to 451) –712 (–1,460 to 35) –242 (–896 to 412) 214 (–442 to 870) –292 (–779 to 196) –270 (–647 to 108) –178 (–551 to 195) MMEFR –198 (–388 to –8)* –165 (–447 to 117) –238 (–478 to 2) –320 (–681 to 41) –307 (–627 to 14) –58 (–379 to 263) –250 (–788 to 288) –409 (–879 to 60) –402 (–875 to 70) –154 (–583 to 275) –48 (–559 to 463) –266 (–666 to 134) –223 (–495 to 49) –185 (–449 to 79) aThe β-coefﬁcient estimates the expected change in lung function as 1,4-DCB increases from the 10th to 90th percentile (3.76 µg/L) on the natural log scale. bIncludes all race/ethnicity groups. Models were adjusted for race/ethnicity, sex, age, age-squared, standing height, body mass index, self-reported doctor diagnosis of emphysema, smoking status, number of cig- arettes smoked per day, years smoked, and serum cotinine levels. Stratiﬁed models exclude variables used for stratiﬁcation. *β-Coefﬁcient differs from 0 at p < 0.05. VOLUME 114 | NUMBER 8 | August 2006 • Environmental Health Perspectives