–346 mL/sec (95% CI, –667 to –24), respec- tively, compared with participants in the low- est decile. This compares with a 100-mL deﬁcit in FEV1 for the highest tertile of serum cotinine in nonsmoking females in the NHANES III population (Eisner 2002). Because we conducted separate analyses for 11 different VOCs, it is possible that the statistical significance of the inverse associa- tion between 1,4-DCB and pulmonary func- tion occurred by chance. However, this seems unlikely given the consistent results across subgroup analyses. Furthermore, an analysis of pulmonary function and 2,5-DCP, the uri- nary metabolite of 1,4-DCB, resulted in simi- lar associations, with the result for FEV1 reaching statistical significance, despite the smaller sample size. It is possible that 1,4-DCB blood concen- trations may reflect exposure better than do blood concentrations of other VOCs, because air and blood concentrations are better corre- lated for 1,4-DCB (Sexton et al. 2005a). In the School Health Initiative: Environment, Learning, Disease (SHIELD) study, 2-day integrated personal air samples of indoor VOCs were taken immediately before taking VOC blood measurements from 143 children in Minneapolis (Sexton et al. 2005a). Personal air samples and VOC blood mea- surements were taken four times over 2 years. Among the VOCs measured, only 1,4-DCB had a high correlation between air and blood concentrations (R2 = 0.79). Except for ace- tone and 2-butanone, that study measured the same VOCs we included in our analyses. Although VOCs generally do not persist in the blood after termination of acute exposure (Ashley and Prah 1997), after frequent pro- longed exposures, blood concentrations can )L 200 A (sm100 t en 0 c ff i –100 e co–200 1 EV–300 F –400 0.10 0.14 0.18 0.23 0.31 0.45 0.70 1.40 4.40 > 4.40 Decile of 1,4-DCB (μg/L) ) c e /sL 200 B (m100 s tn 0 e fic–100 f oe–200 c FR–300 E M–400 0.10 0.14 0.18 0.23 0.31 0.45 0.70 1.40 4.40 > 4.40 M Decile of 1,4-DCB (μg/L) Figure 1. Changes in FEV1 (A) and MMEFR (B) (with 95% CIs) for each decile of 1,4-DCB concentration among 846 participants in the NHANES III (1988–1994). reflect chronic exposures (Ashley and Prah 1997; Ashley et al. 1994; Sexton et al. 2005a, 2005b). For example, examination of the uptake and elimination of some VOCs has sug- gested that bioaccumulation may occur in mul- tiple storage sites in the human body (Ashley and Prah 1997). In the SHIELD study, the between-child variability of 1,4-DCB blood concentrations greatly exceeded the within- child variability (ratio = 434), suggesting that one blood measurement of 1,4-DCB is a good indication of an individual’s blood concentra- tion over time. In contrast, other VOCs had much lower ratios of between- and within-child variability; for example, the next highest were for TCE (ratio = 2), ethylbenzene (ratio ~ 1), and 1,1,1-TCE (ratio ~ 1). The high ratio of between- to within-child variability for 1,4-DCB was not seen in the younger children of the Developmental Research on Attention and Memory Skills (DREAMS) study, but far fewer children had more than one blood sample to estimate the ratio of within- to between-child variability (e.g., 126 in the SHIELD study compared with 22 in the DREAMS study) (Sexton et al. 2005b). Apart from the findings in the SHIELD study (Sexton et al. 2005a), little is known about the relationship between personal 1,4-DCB exposures and blood concentrations. Based on data from a graph of this relationship in children (Sexton et al. 2005a), we estimate that a 1,4-DCB blood concentration of 10 µg/L may correspond to personal exposures of 102 µg/m3 or greater, which is close to the pro- posed chronic duration minimal risk limit (120 µg/m3) [Agency for Toxic Substances and Disease Registry (ATSDR) 2004]. Blood levels of 1,4-DCB were higher in children from the SHIELD study than in the NHANES III adults we studied. For example, the 95th per- centile was 11.03 µg/L for NHANES III and 27.00 µg/L for the SHIELD study. If 1,4- DCB air concentrations can be extrapolated from blood concentrations, it is possible that the highest blood concentrations of 1,4-DCB in NHANES III represent exposures to air concentrations greater than the proposed chronic duration minimal risk limit. People who use air fresheners, toilet bowl deodorants, and mothballs have potential for high exposure to 1,4-DCB because it is an important component of these products (ATSDR 2004; Churchill et al. 2001). However, exposure also occurs in the absence of these products as the compound is com- mon in indoor environments. For example, the U.S. Environmental Protection Agency’s Total Exposure Assessment Methodology (TEAM) study in 1987 found 1,4-DCB in the air of 80% of the homes surveyed (Wallace et al. 1987), although only one-third of the homes used products containing 1,4-DCB (Wallace 1991). The ﬁnding that 96% of the Environmental Health Perspectives • VOLUME 114 | NUMBER 8 | August 2006 VOCs and pulmonary function in NHANES III NHANES III subset had detectable 1,4-DCB blood concentrations (Hill et al. 1995a) is fur- ther evidence that exposure is common (Sampson et al. 1994). Although 1,4-DCB is common in indoor environments, little is known about its effects on human health. Hepatic, dermatologic, and respiratory effects have been reported with acute exposures, but these case reports lack clear information about exposure levels (ATSDR 2004; National Institutes of Health 2005). Data from a single occupational study of 58 men (Hollingsworth et al. 1956) were used in conjunction with animal studies to derive acute and chronic exposure levels in the air consid- ered to pose the minimal risk to humans (ATSDR 2004). Because these limits are derived mostly from animal studies, uncertainty factors are used for extrapolation to humans. The minimal risk limits for human exposure to 1,4-DCB are 2 ppm (12 mg/m3) for acute duration (≤ 24 hr), 0.1 ppm (0.6 mg/m3) for intermediate duration (> 14 days but < 1 year), and 0.02 ppm (0.12 mg/m3) for chronic dura- tion (up to a lifetime) (ATSDR 2004). Among the studies that have measured 1,4-DCB air or blood concentrations (Delﬁno et al. 2003; Hollingsworth et al. 1956; Rumchev et al. 2005; Sexton et al. 2005a, 2005b; Wallace et al. 1987, 1991), only three measured health outcomes (Delfino et al. 2003; Hollingsworth et al. 1956; Rumchev et al. 2005). Of these, only two measured res- piratory outcomes and included only children. In one study, children 6 months to 3 years of age (n = 88) had higher odds of asthma with increasing indoor air concentrations of 1,4-DCB (Rumchev et al. 2005). In a panel study of 22 asthmatic children 10–16 years of age, respiratory symptoms were associated with outdoor air concentrations of total VOCs but not with 1,4-DCB alone (Delfino et al. 2003). Children in this study measured morn- ing and evening peak flow; no relationship with any VOC was observed. No other pul- monary measures were tested. As expected, outdoor air concentrations of 1,4-DCB were low (0.3–3.0 µg/m3). Indoor air concentrations of 1,4-DCB are signiﬁcantly greater than outdoor air concen- trations (Wallace et al. 1987). For example, the TEAM study measured mean personal exposures of 21 µg/m3 and indoor concentra- tions of 30 µg/m3, compared with outdoor concentrations of 2.0 µg/m3 (Wallace et al. 1987). According to other measures, levels in some homes and public restrooms may reach almost 1.64 mg/m3 (ATSDR 2004), which is greater than the minimal risk limit for chronic exposure. The chronic duration minimal risk limit is based on observed eosinophilic changes in the olfactory epithelium of rats; no information was available on effects of exposure on pulmonary 1213