Volatile Organic Compounds in Human Milk: Methods and

Feb 1, 2007 - In Baltimore, indoor air VOC concentrations in the respective ... Polycyclic Aromatic Hydrocarbons in Human Milk of Nonsmoking U.S. Wome...
10 downloads 0 Views 220KB Size
Download PDF
Environ. Sci. Technol. 2007, 41, 1662-1667

Volatile Organic Compounds in Human Milk: Methods and Measurements SUNG R. KIM, ROLF U. HALDEN, AND TIMOTHY J. BUCKLEY* Department of Environmental Health Sciences (Room W7014), Johns Hopkins School of Public Health, 615 North Wolfe Street, Baltimore, Maryland 21205

The present study was conducted to optimize methods for measurement of volatile organic compounds (VOCs) by use of headspace solid-phase microextraction (HS-SPME) and to provide a preliminary assessment of levels in human milk. MTBE (methyl tert-butyl ether), chloroform, benzene, and toluene were measured from two sources of milk: a North Carolina milk bank (n ) 5) and multiple samples from three women within nonsmoking households in inner-city Baltimore, MD (n ) 8). In Baltimore, indoor air VOC concentrations in the respective households were also measured by active sampling and thermal desorption gas chromatography/mass spectrometry in selective ion monitoring (GC/MS/SIM) over each of the 3 days of milk collection. By application of these optimized methods, we observed median VOC concentrations in Baltimore human milk of 0.09, 0.55, 0.12, and 0.46 ng/mL for MTBE, chloroform, benzene, and toluene, respectively. For benzene, toluene, and MTBE, milk levels trended with observed indoor air concentrations. On the basis of measured concentrations in air and milk, infant average daily dose by inhalation exceeded ingestion rates by 25-135-fold. Thus, VOC exposure from breast milk is vastly exceeded by that from indoor air in nonsmoking households. Accordingly, strategies to mitigate infant VOC exposure should focus on the indoor air inhalation pathway of exposure.

Introduction In many respects, human milk can be considered as a sentinel matrix for assessing human health threats from environmental agents. Milk is a biological matrix that is both susceptible to the bioaccumulation of environmental toxics and has great relevance for human health (1). Its susceptibility stems from the preferential uptake and bioaccumulation of lipophilic toxics such as tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and polybrominated diphenyl ethers (PBDEs) (2, 3). Its human health relevance relates to the fact that it represents information for two susceptible populations, that is, body burden of the nursing mother and ingested dose of the infant (4). Human milk is important to the health and well-being of a growing infant and its mother (5). The nursing infant may be particularly vulnerable due to exposure from the combination of inhalation and ingestion pathways, their high ingestion and ventilation rates relative to body * Corresponding author. Present address: The Ohio State University School of Public Health, 320 West 10th Street, Columbus, OH 43210; phone: (614) 293-7161; fax: (614) 293-6485; e-mail: [email protected]. 1662

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 41, NO. 5, 2007

mass and surface area, and less well developed detoxification systems (6). Therefore, human milk serves as a valuable biological matrix for the assessment of public and environmental health (7). Despite the relevance of human milk as an indicator of environmental health, little is known about the partitioning of VOCs into this important biological matrix. The tendency for an environmental chemical to partition into human milk is largely defined by its lipophilicity. The lipophilicity of a chemical is experimentally determined by its tendency to partition into octanol in an octanol-water mixture, that is, its octanol-water partition coefficient (Kow). The greater its Kow value, the more lipophilic the chemical is and the more likely it is to be found in milk. Needham and Wang (8) recently described the bioaccumulation of some volatile and/or semivolatile organic compounds including persistent organic chemicals and metals in human milk. Even though the logarithmic Kow values for most VOCs (typically 2.0-2.7) are lower than those for some of the more notorious persistent organics such as dioxin, PCBs, and PBDEs (i.e., 6.0 to >8.0), they are still sufficiently high to induce VOC migration across cellular barriers and subsequent accumulation in blood (911) and/or milk fat globules (12). Despite the potential for VOCs to partition from blood into milk, their toxicity (1316) and the ubiquity of environmental exposure (17), very little is known about methods of measurement in milk or the distribution of levels across the U.S. population. Although laboratory-based partition studies have been conducted (18, 19), there have been few literature reports of VOC levels in human milk associated with environmental exposures (20-22). The importance of milk as a sentinel matrix for environmental health is established from numerous studies investigating a variety of adverse health effects associated with environmental chemicals. Most of these studies have focused on organochlorine pesticides, PCBs, and dioxin (3). Although adverse health effects associated with VOCs in human milk have not been studied, their hazard is well-established on the basis of observations from combinations of occupational and environmental studies. Benzene is considered a known human carcinogen (16). Risk of childhood leukemia is increased for benzene exposures of >10 µg/m3 associated with traffic (23) and auto repair garages and gasoline stations (24). Styrene has been associated with neurotoxicity within occupational environments at concentrations >95 mg/m3 (14). Risk of childhood asthma has been shown to increase at total VOC concentrations of >100 µg/ m3 (15). Chloroform is considered a possible human carcinogen (25) with recent studies suggesting an association between duration of chlorinated surface water use and rectal (26) and bladder (27) cancers. Recently, styrene exposure has been identified as a risk factor for breast cancer (28). Accordingly, there is an important need for the development of VOC measurement methods to support exposure and hazard assessment. Despite human milk’s vulnerability to environmental chemical contamination, it is widely acknowledged that the health benefits of nursing far outweigh the risks (7). Therefore, it is important that communication of research results should be carefully considered so as not to dissuade breast-feeding (7). The present study was designed to refine and optimize methods for measuring VOCs in human milk and then apply those methods to nonsmoking women living within the innercity urban environment to obtain a preliminary assessment of the influence of exposure, and dose to the mother and the nursing infant. 10.1021/es062362y CCC: $37.00

 2007 American Chemical Society Published on Web 02/01/2007

Materials and Methods The assessment of VOCs in milk was approached in a stepwise fashion. First, two laboratory-based experiments were conducted to optimize methods of sampling and analysis of milk for VOC analysis. Both experiments used bovine milk that was nonpasteurized and nonhomogenized as a surrogate for human milk. Although there are recognized matrix differences between human and bovine milk (8), other investigators have used a similar approach (20, 29). The first set of experiments was conducted to evaluate the potential for VOC loss during milk expression. The second set of experiments examined the optimal temperature and duration for solid-phase microextraction (SPME) and recovery of analytes from milk spiked with VOC. Together, these experiments ultimately informed the methods employed to assess VOC levels within human milk. Evaluation of VOC Loss during Sample Collection. VOC loss by volatilization during sample collection was assessed in a simulation experiment with nonhomogenized, nonpasteurized whole bovine milk as a surrogate matrix. Bovine milk (40 mL) was added to 40-mL amber vials (n ) 20) that were closed with polytetrafluoroethylene (PTFE) septa. By use of a gastight syringe, the vial septum was pierced and samples were spiked with 20 ng of the individual target VOCs and 8 ng of the corresponding internal standards. Spiked samples were shaken at 100 rpm on an orbital shaker for 12 h at 37 °C to attain equilibration across the fatty suspension as extant in vivo. Although time to equilibration has been shown to occur in 1.5 h for chloroform (18), we conservatively used 12 h within the present study because similar data are not available for the remaining VOCs. Twenty vials were divided into five groups. By use of a gastight syringe, milk was transferred from these five groups (four replicates each) at rates of 8, 4, 2, 1.3, and 0 (control) mL/min into open clean 40-mL vials, simulating different rates of expression of breast milk. Once the milk was completely transferred, VOC concentrations were measured and compared to those of unspiked control samples. Microfilament Extraction Optimization. To optimize the sensitivity of VOC analysis in human milk, with nonhomogenized whole bovine milk as a surrogate matrix, the effect of extraction time (0-90 min) and temperature (20-80 °C in 20 °C steps) was evaluated. Spiked samples (5 mL) were evaluated at a level of 0.2 ng/mL and in triplicate for each time and temperature. All calibration standards were prepared in water rather than human or bovine milk because of the scarcity of human milk and the wide variation of VOC levels found in both bovine and human milk. A similar approach was used by Chambers et al. (30) in their analysis of MTBE in blood. Human Milk Collection. From May to July 2005, three lactating mothers living in inner-city Baltimore provided a milk sample of approximately 40 mL every morning over three consecutive days. Samples were collected while participants were home so there was no need to travel prior to collection. Participants reported an elapsed time of approximately 2 h from their previous nursing to sample collection. Participants were instructed to manually express milk into precleaned and labeled 120-mL screw-cap glass jars sealed with a Teflon-lined screw cap provided by the Centers for Disease Control and Prevention (CDC). After collection, the milk was transferred within 15 min into a prelabeled 5 mL amber vial that was then sealed with a Teflonlined screw cap. The vial was completely filled so that there was no headspace. Human milk samples were delivered to the Johns Hopkins Bloomberg School of Public Health laboratory and stored at -80 °C until analyzed. All analyses were conducted within a week of sample collection. Because indoor air sampling was limited to Baltimore homes, correlation with milk levels is only available for these homes.

Five additional human milk samples (100 mL/sample) were obtained from unidentified consenting donors from the WakeMed milk bank in Raleigh, NC. As with the Baltimore mothers, these samples were collected while at home. However, the procedure differed from the Baltimore samples in that these samples were collected with a pump and the elapsed time between previous nursing and sample collection was 3-4 h. The milk bank samples were decanted from the pump reservoir into 4 oz plastic milk bags and placed into the home freezer until shipped to the WakeMed milk bank where they were stored at -20 °C. Samples were stored at WakeMed 0.05) in concentration over the 30 min transfer period. With vapor pressures ranging from 22 mmHg (toluene) to 249 mmHg (MTBE) (38), the assessment of true VOC concentrations in milk must consider sample losses by volatilization during the sampling. Observed losses were consistent with what would be predicted from vapor pressure (i.e., 249, 160, 75, and 22 mmHg at 20 °C) (R2 ) 0.92) or from Henry’s law constant (0.026, 0.16, 0.23, and 0.26 at 25 °C) (R2 ) 0.89) for MTBE, chloroform, benzene, and toluene, respectively (39, 40). Milk collection by pump rather than manual expression can hasten collection by approximately 2-fold, that is, 3-4 mL/min (41, 42), and therefore potentially limit volatility losses. However, additional research will be required to evaluate whether such gains will be offset by new losses caused by the negative pressure produced by the pump or milk contamination from VOCs emanating from the pump or collection bottle. Concentration of VOCs in Human Milk. Using the optimized analytical conditions above, we analyzed eight Baltimore human milk samples. The observed VOC concentrations varied by analyte with the highest median value observed for chloroform (0.55 ng/mL), followed by toluene

FIGURE 1. Distribution of VOC levels in human milk. The top and bottom of the box indicate the 25th and 75th percentiles, respectively, and the vertical line in between indicates the median. The “whiskers” indicate the 10th and 90th percentile, and outlying data points are shown as symbols. (0.46 ng/mL), benzene (0.12 ng/mL), and MTBE (0.09 ng/ mL) (Figure 1). For the NC milk bank samples (n ) 5), concentrations were comparable but the rank order was slightly different: toluene was highest (0.56), followed by chloroform (0.14), benzene (0.06), and MTBE below the limit of detection set at 1/2 DL ) (0.005 ng/mL). Ranges across the two sample sets expressed as the 10th-90th percentile were 0.1-1.0, 0.2-1.1, 0.01-0.2, and 0.005-0.11 ng/mL for chloroform, toluene, benzene, and MTBE, respectively. Interpretation of the differences between Maryland and North Carolina results is limited because the influence of differences in methods of collection and storage is unclear. The rank order of VOC indoor air concentrations differed from what was observed in milk, with the highest median observed for toluene (4.1 µg/m3), followed by MTBE (4.0 µg/m3), chloroform (3.4 µg/m3), and benzene (1.0 µg/m3). Despite its public health relevance, there are few reports of VOC levels in human milk. Fabietti et al. (21) reported concentrations for 23 women living in Rome, Italy. Whereas we observed median levels of benzene and toluene of 0.12 and 0.46 ng/mL (Baltimore samples) and 0.06 and 0.56 ng/ mL (milk bank samples), respectively, Fabietti et al. reported lower levels of 0.06 and 0.40 ng/mL. The benzene levels of the Baltimore samples were significantly greater (p < 0.05) than what was observed in the Italian study, whereas toluene levels were statistically indistinguishable (p g 0.05) (Figure 1). Because both studies suffer from a small and nonrepresentative sample and Fabietti et al. do not describe their methodology for milk collection, it is difficult to ascribe too much meaning to the observed differences, however. Association between the Level of VOCs in Milk and Indoor Air. A comparison of the level of VOCs in milk to the indoor air concentration showed a suggestive positive association for toluene, benzene, and MTBE (Figure 2). The Spearman correlation coefficients were significant (p < 0.05) for all three of the respective VOCs, that is, 0.60, 0.40, and 0.48, even though the sample number was very small. This predictive association implicates air contamination as the likely source for concentrations found in milk. Since inhalation is the dominant pathway of exposure and leads to milk levels, effective prevention strategies will have to target the inhalation pathway of exposure. In contrast to these three mobile source-related VOCs, for chloroform there was no apparent relationship (r ) 0.07, p > 0.05). There are multiple likely explanations for the observed lack of association. First, exposure occurs not only through inhalation but also through the here not examined water ingestion and dermal absorption while showering or

FIGURE 2. Scatter plots comparing VOC concentrations measured indoors and in human milk. Different individuals are represented by different symbols. bathing (43). Second, because of the high inhalation exposures occurring within the bath/shower, even this route of exposure was probably poorly captured by the indoor living room sampling (44). Third, ingested chloroform will undergo first-pass metabolism within the liver so that only metabolites of chloroform will reach the circulating blood stream and be available for partitioning into milk (45, 46). Since drinking water is the source of exposure via all three pathways (i.e., dermal, inhalation, and ingestion), strategies for chloroform exposure reduction will target this source. The median indoor VOC levels measured in the present study are comparable to what has been reported from across the United States (47-50). Therefore, it is likely that the VOC milk levels we observed are typical for the United States. Furthermore, the analytical methods employed here are likely to have practical relevance to other studies conducted in the United States. Infant Relative Dose Contribution. On the basis of the air concentrations observed above, we estimate median inhaled doses of 2150, 2700, 1020, and 4540 ng (kg body weight)-1 day-1 for MTBE, chloroform, benzene, and toluene, while the dose from milk ingestion was 16, 108, 23, and 89 ng kg-1 day-1, respectively. Accordingly, across the four VOCs, the dose from inhalation exceeded that from ingested milk by a factor of 25-135. The distribution of inhaled to ingested doses is shown in Figure 3. Since there are no health-based guidelines or standards for chemicals in human milk, we compare our observed concentrations in milk to the EPA’s Safe Drinking Water standards and reference dose (RfD) to provide some perspective of health risk for infants. The drinking water maximum contaminant levels (MCL) for chloroform, benzene, and toluene (MTBE and chloroform are not specifically regulated; in the case of chloroform, the MCL for total trihalomethanes was used) are 100, 5, and 1000 ng/mL, respectively (51). These concentrations exceed our observed median milk levels from Baltimore by factors of 180, 40, and 2170, respectively. A margin of exposure (MOE) analysis (ratio of RfD to estimated dose) was also conducted to assess the health threat associated with nonlinear effects of our target analytes, that is, for chloroform, “moderate/marked fatty cyst formation in the liver”; for benzene, “decreased lymphocyte count”; and for toluene, “increased kidney weight” (52). This VOL. 41, NO. 5, 2007 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

1665

FIGURE 3. Infant dose ratio: inhalation to ingestion based on estimates from Baltimore indoor air and human milk measurements, respectively. Dose is calculated as the average daily dose (ADD, nanograms per kilogram per day) from eqs 1 and 2 for each target VOC. analysis revealed MOEs of 93 (10/0.108), 174 (4/0.023), and 899 (80/0.089), respectively, demonstrating that the observed doses from milk ingestion were well below these threshold levels of health concern. Even though the present study indicates that inhalation is the dominant route of exposure, health risk can also be influenced by the route of exposure. An ingested VOC dose will undergo first-pass metabolism within the liver before becoming systemically available. Depending on whether the parent VOC is activated or deactivated through first-pass liver metabolism will influence whether an ingested VOC dose is less or more toxic than an inhaled dose. On the basis of physiologically based pharmacokinetic (PBPK) modeling, for chloroform it has been shown that inhalation or dermal exposure will yield a higher dose to the bladder relative to ingestion. The converse is true for the liver, where an ingested dose results in higher concentrations (53, 43). This preliminary study gives a practical way to measure VOC concentrations in human milk. We observed that the infant dose from inhalation exceeded that from milk ingestion by approximately 25-135-fold. Furthermore, for the mobile source-related VOCs, there was suggestive evidence that the observed milk concentrations were related to indoor air levels, implying that air control strategies would have the dual advantage of reducing infant inhalation and ingestion exposures. For mobile source-related VOCs where inhalation is the dominant pathway of exposure, it indicates for the first time that indoor VOC levels can be an important determinant for levels found in breast milk. These study results in no way suggest that human milk is anything but the absolute best source of nutrition for a growing infant.

Acknowledgments This study was supported through pilot funding from the Johns Hopkins NIEHS Center for Urban Environmental Health (P30ES03819), the Johns Hopkins Center for a Livable Future, and the U.S. EPA (R829175). We acknowledge Ms. Mancini and Drs. Blount, Andresen, and LaKind for their advice and support. We are especially grateful to the nursing mothers who agreed to participate.

Literature Cited (1) Pronczuk, J.; Akre, J.; Moy, G.; Vallenas, C. Global Perspectives in Breast Milk Contamination: Infectious and Toxic Hazards. Environ. Health Perspect. 2002, 110, A349-A351. (2) LaKind, J. S.; Berlin, C. M.; Naiman, D. Q. Infant Exposure to Chemicals in Breast Milk in the United States: What We Need to Learn From a Breast Milk Monitoring Program. Environ. Health Perspect. 2001, 109, 75-88. 1666

9

ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 41, NO. 5, 2007

(3) Solomom, G. M.; Weiss, P. M. Chemical Contaminants in Breast Milk: Time Trends and Regional Variability. Environ. Health Perspect. 2002, 110, 339-347. (4) Diehl-Jones, W. L.; Bols, N. C. Use of Response Biomarkers in Milk for Assessing Exposure to Environmental Contaminants: the Case for Dioxin-Like Compounds. J. Toxicol. Environ. Health B: Crit. Rev. 2000, 3, 79-107. (5) American Academy of Pediatrics. Breastfeeding and the Use of Human Milk. Pediatrics 2005, 115, 495-506. (6) Goldman, L. R.; Koduru, S. Chemicals in the environment and developmental toxicity to children: a public health and policy perspective. Environ. Health Perspect. 2000, 108 (Suppl. 3), 443448. (7) Lakind, J. S.; Birnbach, N.; Borgert, C. J.; Sonawane, B. R.; Tully, M. R.; Freidman, L. Human Milk Surveillance and Research of Environmental Chemicals: Concepts for Consideration in Interpreting and Presenting Study Results. J. Toxicol. Environ. Health, Part A 2002, 65, 1909-1928. (8) Needham, L. L.; Wang, R. Y. Analytic Considerations for Measuring Environmental Chemicals in Breast Milk. Environ. Health Perspect. 2002, 110, A317-A324. (9) Berlin, M.; Gage, J. C.; Gullberg, B.; Holm, S.; Knutsson, P.; Eng, C.; Tunek, A. Breath Concentration As an Index of the Health Risk From Benzene. Studies on the Accumulation and Clearance of Inhaled Benzene. Scand. J. Work Environ. Health 1980, 6, 104-111. (10) Brugnone, F.; Perbellini, L.; Wang, G. Z.; Maranelli, G.; Raineri, E.; De Rosa, E.; Saletti, C.; Soave, C.; Romeo, L. Blood Styrene Concentrations in a “Normal” Population and in Exposed Workers 16 Hours After the End of the Workshift. Int. Arch. Occup. Environ. Health 1993, 65, 125-130. (11) Nise, G.; Orbaek, P. Toluene in Venous Blood During and After Work in Rotogravure Printing. Int. Arch. Occup. Environ. Health 1988, 60, 31-35. (12) Jensen, A. A.; Slorach, S. A. Chemical Contaminants in Human Milk; CRC Press: Boca Raton, FL, 1990. (13) Wichmann, G.; Muhlenberg, J.; Fischader, G.; Kulla, C.; Rehwagen, M.; Herbarth, O.; Lehmann, I. An Experimental Model for the Determination of Immunomodulating Effects by Volatile Compounds. Toxicol. In Vitro 2005, 19, 685-693. (14) Tsai, S. Y.; Chen, J. D. Neurobehavioral Effects of Occupational Exposure to Low-Level Styrene. Neurotoxicol. Teratol. 1996, 18, 463-469. (15) Wieslander, G.; Norback, D.; Bjornsson, E.; Janson, C.; Boman, G. Asthma and the Indoor Environment: the Significance of Emission of Formaldehyde and Volatile Organic Compounds From Newly Painted Indoor Surfaces. Int. Arch. Occup. Environ. Health 1997, 69, 115-124. (16) WHO IARC. IARC Monogr. Eval. Carcinog. Risk Chem. Hum. 1987 (Suppl. 7). (17) Adgate, J. L.; Church, T. R.; Ryan, A. D.; Ramachandran, G.; Fredrickson, A. L.; Stock, T. H.; Morandi, M. T.; Sexton, K. Outdoor, Indoor, and Personal Exposure to VOCs in Children. Environ. Health Perspect. 2004, 112, 1386-1392. (18) Batterman, S.; Zhang, L.; Wang, S.; Franzblau, A. Partition Coefficients for the Trihalomethanes Among Blood, Urine, Water, Milk and Air. Sci. Total Environ 2002, 284, 237-247. (19) Fisher, J.; Mahle, D.; Bankston, L.; Greene, R.; Gearhart, J. Lactational Transfer of Volatile Chemicals in Breast Milk. Am. Ind. Hyg. Assoc. J. 1997, 58, 425-431. (20) Pellizzari, E. D.; Hartwell, T. D.; Harris, B. S., III; Waddell, R. D.; Whitaker, D. A.; Erickson, M. D. Purgeable Organic Compounds in Mother’s Milk. Bull. Environ. Contam. Toxicol. 1982, 28, 322328. (21) Fabietti, F.; Ambruzzi, A.; Delise, M.; Sprechini, M. R. Monitoring of the Benzene and Toluene Contents in Human Milk. Environ. Int. 2004, 30, 397-401. (22) Schreiber, J. S. Predicted infant exposure to tetrachloroethene in human breastmilk. Risk Anal.1993, 13, 515-24. (23) Crosignani, P.; Tittarelli, A.; Borgini, A.; Codazzi, T.; Rovelli, A.; Porro, E.; Contiero, P.; Bianchi, N.; Tagliabue, G.; Fissi, R.; Rossitto, F.; Berrino, F. Childhood Leukemia and Road Traffic: A Population-Based Case-Control Study. Int. J. Cancer 2004, 108, 596-599. (24) Steffen, C.; Auclerc, M. F.; Auvrignon, A.; Baruchel, A.; Kebaili, K.; Lambilliotte, A.; Leverger, G.; Sommelet, D.; Vilmer, E.; Hemon, D.; Clavel, J. Acute Childhood Leukaemia and Environmental Exposure to Potential Sources of Benzene and Other Hydrocarbons; a Case-Control Study. Occup. Environ. Med. 2004, 61, 773-778. (25) WHO IARC. IARC Monogr. Eval. Carcinog. Risk Chem. Hum. 1999, 73, 131.

(26) Hildesheim, M. E.; Cantor, K. P.; Lynch, C. F.; Dosemeci, M.; Lubin, J.; Alavanja, M.; Craun, G. Drinking Water Source and Chlorination Byproducts. II. Risk of Colon and Rectal Cancers. Epidemiology 1998, 9, 29-35. (27) Cantor, K. P.; Lynch, C. F.; Hildesheim, M. E.; Dosemeci, M.; Lubin, J.; Alavanja, M.; Craun, G. Drinking Water Source and Chlorination Byproducts. I. Risk of Bladder Cancer. Epidemiology 1998, 9, 21-28. (28) Coyle, Y. M.; Hynan, L. S.; Euhus, D. M.; Minhajuddin, A. T. An ecological study of the association of environmental chemicals on breast cancer incidence in Texas. Breast Cancer Res. Treat. 2005, 92, 107-114. (29) Needham, L. L.; Ryan, J. J.; Furst, P. Guidelines for Analysis of Human Milk for Environmental Chemicals. J Toxicol. Environ. Health A 2002, 65, 1893-1908. (30) Chambers, D. M.; McElprang, D. O.; Mauldin, J. P.; Hughes, T. M.; Blount, B. C. Identification and Elimination of Polysiloxane Curing Agent Interference Encountered in the Quantification of Low-Picogram Per Milliliter Methyl tert-Butyl Ether in Blood by Solid-Phase Microextraction Headspace Analysis. Anal. Chem. 2005, 77, 2912-2919. (31) Fang, F.; Hong, C. S.; Chu, S.; Kou, W.; Bucciferro, A. Reevaluation of headspace solid-phase microextraction and gas chromatography-mass spectrometry for the determination of methyl tertbutyl ether in water samples. J. Chromatogr. A 2003, 1021, 157164. (32) Bonin, M. A.; Silva, L. K.; Smith, M. M.; Ashley, D. L.; Blount, B. C. Measurement of trihalomethanes and methyl tert-butyl ether in whole blood using gas chromatography with highresolution mass spectrometry. J. Anal. Toxicol. 2005, 29, 8189. (33) Cardinali, F. L.; Ashley, D. L.; Morrow, J. C.; Moll, D. M.; Blount, B. C. Measurement of trihalomethanes and methyl tertiarybutyl ether in tap water using solid-phase microextraction GCMS. J. Chromatogr. Sci. 2004, 42, 200-206. (34) U.S. EPA. Child-specific exposure factors handbook; EPA-600P-00-002.B; U.S. Environmental Protection Agency: Washington, DC, 2002. (35) Buckley, T. J.; Prah, J. D.; Ashley, D.; Zweidinger, R. A.; Wallace, L. A. Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE). J Air Waste Manage. Assoc. 1997, 47, 739-752. (36) Lindstrom, A. B.; Pleil, J. D.; Berkoff, D. C. Alveolar Breath Sampling and Analysis to Assess Trihalomethane Exposures During Competitive Swimming Training. Environ. Health Perspect. 1997, 105, 636-642. (37) Wallace, L. A.; Pellizzari, E. D. Recent Advances in Measuring Exhaled Breath and Estimating Exposure and Body Burden for Volatile Organic Compounds (VOCs). Environ. Health Perspect. 1995, 103 (Suppl. 3), 95-98. (38) U.S. EPA. Method TO-15: The Determination of Volatile Organic Compounds in Air Collected in Specially-Prepared Canisters and Analyzed by Gas Chromatography/Mass Spectrometry (GC/ MS). U.S. Environmental Protection Agency: Cincinnati, OH, 1999. (39) Miller, M. E.; Stuart, J. D. Measurement of Aqueous Henry’s Law Constants for Oxygenates and Aromatics Found in Gasolines by the Static Headspace Method. Anal. Chem. 2000, 72, 622625. (40) Gorgenyi, M.; Dewulf, J.; Van Langenhove, H. Temperature Dependence of Henry’s Law Constant in an Extended Tem-

perature Range. Chemosphere 2002, 48, 757-762. (41) Fewtrell, M. S.; Lucas, P.; Collier, S.; Singhal, A.; Ahluwalia, J. S.; Lucas, A. Randomized Trial Comparing the Efficacy of a Novel Manual Breast Pump With a Standard Electric Breast Pump in Mothers Who Delivered Preterm Infants. Pediatrics 2001, 107, 1291-1297. (42) Paul, V. K.; Singh, M.; Deorari, A. K.; Pacheco, J.; Taneja, U. Manual and Pump Methods of Expression of Breast Milk. Indian J. Pediatr. 1996, 63, 87-92. (43) Weisel, C. P.; Jo, W. K. Ingestion, Inhalation, and Dermal Exposures to Chloroform and Trichloroethene From Tap Water. Environ. Health Perspect. 1996, 104, 48-51. (44) Lindstrom, A. B.; Pleil, J. D.; Berkoff, D. C. Alveolar Breath Sampling and Analysis to Assess Trihalomethane Exposures During Competitive Swimming Training. Environ. Health Perspect. 1997, 105, 636-642. (45) Ashley, D. L.; Blount, B. C.; Singer, P. C.; Depaz, E.; Wilkes, C.; Gordon, S.; Lyu, C.; Masters, J. Changes in Blood Trihalomethane Concentrations Resulting From Differences in Water Quality and Water Use Activities. Arch. Environ. Occup. Health 2005, 60, 7-15. (46) Backer, L. C.; Ashley, D. L.; Bonin, M. A.; Cardinali, F. L.; Kieszak, S. M.; Wooten, J. V. Household Exposures to Drinking Water Disinfection by-Products: Whole Blood Trihalomethane Levels. J. Exposure Anal. Environ. Epidemiol. 2000, 10, 321-326. (47) Adgate, J. L.; Eberly, L. E.; Stroebel, C.; Pellizzari, E. D.; Sexton, K. Personal, Indoor, and Outdoor VOC Exposures in a Probability Sample of Children. J. Exposure Anal. Environ. Epidemiol. 2004, 14 (Suppl. 1), S4-S13. (48) Clayton, C. A.; Pellizzari, E. D.; Whitmore, R. W.; Perritt, R. L.; Quackenboss, J. J. National Human Exposure Assessment Survey (NHEXAS): Distributions and Associations of Lead, Arsenic and Volatile Organic Compounds in EPA Region 5. J. Exposure Anal. Environ. Epidemiol. 1999, 9, 381-392. (49) Sexton, K.; Adgate, J. L.; Ramachandran, G.; Pratt, G. C.; Mongin, S. J.; Stock, T. H.; Morandi, M. T. Comparison of Personal, Indoor, and Outdoor Exposures to Hazardous Air Pollutants in Three Urban Communities. Environ. Sci. Technol. 2004, 38, 423-430. (50) Gordon, S. M.; Callahan, P. J.; Nishioka, M. G.; Brinkman, M. C.; O’Rourke, M. K.; Lebowitz, M. D.; Moschandreas, D. J. Residential Environmental Measurements in the National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Arizona: Preliminary Results for Pesticides and VOCs. J. Exposure Anal. Environ. Epidemiol. 1999, 9, 456-470. (51) U.S. EPA. List of Contaminants & their Maximum Contaminant Level (MCLs) . Available at http://www.epa.gov/safewater/ mcl.html [accessed 1 April 2006]. (52) U.S. EPA. Integrated risk information system. Available at http:// www.epa.gov/iris [accessed 1 April 2006]. (53) Blancato, J. N.; Chiu, N. Predictive Modeling for Uptake and Tissue Distribution From Human Exposures. In Safety of Water Disinfection: Balancing Chemical and Microbial Risks; Craum, G. F., Ed.; ILSI Press: Washington, DC, 1993.

Received for review October 3, 2006. Revised manuscript received November 27, 2006. Accepted December 18, 2006. ES062362Y

VOL. 41, NO. 5, 2007 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

9

1667