Article pubs.acs.org/est
Measurement of Phthalates in Skin Wipes: Estimating Exposure from Dermal Absorption Mengyan Gong,† Yinping Zhang,† and Charles J. Weschler*,†,‡ †
Department of Building Science, Tsinghua University, Beijing 10084, China Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey 08854, United States
‡
S Supporting Information *
ABSTRACT: This study has determined the levels of six phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), di(isobutyl) phthalate (DiBP), di(n-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP)) in skin wipes; examined factors that might influence the levels, including body location, time of sampling, and hand-washing; and estimated dermal absorption based on the measured levels. Skin wipes were collected from the forehead, forearm, back-of-hand, and palm of 20 participants using gauze pads moistened with isopropanol. DiBP, DnBP, and DEHP were most frequently detected; DEHP levels were substantially higher than DnBP and DiBP levels, and DnBP levels were somewhat lower than DiBP levels. The levels differed at different body locations, with palm > back-of-hand > forearm ≥ forehead. Repeated wipe sampling from six participants over a 1 month period indicated that levels at the same body location did not vary significantly. The estimated median total dermal absorption from skin surface lipids on the palm, back-of-hand, arm, and head are 0.48, 0.68, and 0.66 (μg/kg)/day for DiBP, DnBP, and DEHP, respectively. These estimates are roughly 10−20% of the total uptake reported for Chinese adults and suggest that dermal absorption contributes significantly to the uptake of these phthalates. Washing with soap and water removed more than 50% of the phthalates on the hands and may be a useful tool in decreasing aggregate phthalate exposure.
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INTRODUCTION Phthalate esters are a group of chemicals widely used in many consumer products. Higher molecular weight phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBzP), are mainly used as plasticizers in poly(vinyl chloride) (PVC) and other polymers, while lower molecular weight phthalates, such as dimethyl phthalate (DMP) and diethyl phthalate (DEP), are often used as solvents or carriers in personal care products, varnishes, and coatings.1−3 Di(nbutyl) phthalate (DnBP) and di(isobutyl) phthalate (DiBP) are used in both applications. Annually, over 470 million pounds of phthalates are produced globally.4 Since they are not chemically bound to the products in which they are used, they can be gradually released into the environment5,6 and have been detected in multiple media including indoor dust and air7−10 as well as food.11,12 The occurrence of phthalate metabolites in human urine, blood, and breast milk is indicative of widespread human exposure to phthalates.13−16 Exposure to certain phthalates may be associated with adverse health effects (e.g., neurodevelopment problems,17 low semen quality,18,19 miscarriages,20 asthma and allergies,21,22 and obesity23). Humans are exposed to phthalates through inhalation, dermal absorption, and ingestion, including dietary ingestion and indirect ingestion. Dietary ingestion appears to be the primary exposure route for DEHP,12,24−26 while for other common phthalates (e.g., DMP, DEP, DiBP, DnBP, and BBzP) © 2014 American Chemical Society
inhalation, dermal absorption, and dust ingestion appear to make significant contributions.10,12,26,27 Dermal contact with consumer products was assessed to be the major exposure pathway for DMP, DEP, and BBzP in an evaluation of sources of phthalate exposure among Europeans.27 A study which detected phthalates in indoor dust in China reported that dermal exposure was a major contributor to overall DEP exposure.10 Recent studies have suggested that dermal absorption from air may be important for DMP, DEP, DiBP, and DnBP26,28−31 The absorption, metabolism, distribution, and elimination of a chemical are different for different exposure pathways.32 Ingested chemicals pass through the intestines and liver before entering the blood. Inhaled chemicals first pass through the lungs. In contrast, chemicals absorbed via the skin can directly enter the blood.26,28,31 Hence, for comparable exposures, the resulting biologically effective dose to organs may differ for different exposure pathways.33 In addition, dermal exposure to phthalates may affect the local health of the skin.34,35 In light of the preceding discussion, understanding dermal exposure to phthalates is important to properly characterize risk Received: Revised: Accepted: Published: 7428
April 7, 2014 June 5, 2014 June 9, 2014 June 9, 2014 dx.doi.org/10.1021/es501700u | Environ. Sci. Technol. 2014, 48, 7428−7435
Environmental Science & Technology
Article
targeted skin location was wiped four times in succession with the same pad. To examine the potential variability of phthalates levels at different body locations, 10 male and 10 female participants had skin wipes taken from their forehead, right and left forearms, right and left backs-of-hands, and right and left palms. The surface area of a sampled hand was estimated by tracing an outline of the hand shape on cross-hatched graph paper. In the case of skin wipes of the forearm and forehead, a fixed area was sampled by affixing flexible templates to the area sampled; the templates had a 266 cm2 opening for the forearm and a 70 cm2 opening for the forehead. To investigate temporal variability, skin wipes were performed on six participants three times per individual over a 1 month period. To examine the influence of hand-washing, five participants had their left hand sampled for the targeted phthalates prior to washing and their right hand sampled postwashing, while five other participants had their right hand sampled prior to washing and their left hand sampled postwashing. The hand-washing procedure began by transferring approximately 1 mL of liquid soap to the palm; the hands were then moistened with a small amount of water. The subjects proceeded to rub their hands together in a typical “washing” pattern for 15 s. This procedure was then repeated for 20 s during which the hands were kept under flowing water (∼3 L/min), after which the hands were allowed to dry in the air for approximately 5 min prior to sampling. All wipes were extracted and analyzed separately. For each participant a field blank was paired with the collected samples; the field blank was prepared by soaking a gauze pad in 5 mL of isopropanol and placing it directly into a brown glass jar. After performing the skin wipe, each sample was spiked with isotopically labeled recovery standards (diethyl phthalate-d4, 1 μg/sample; di(isobutyl) phthalate-d4, 1 μg/sample; di(2ethylhexyl) phthalate-d4, 5 μg/sample) and stored in a brown glass jar at −20 °C until analysis. Sample Analysis. Each sample was extracted with 120 mL of dichloromethane for 6 h using a Soxhlet extractor. The extracts were concentrated to 25 mL using a rotary evaporator, filtered through a 0.45 μm organic microporous membrane, and finally concentrated, using a gentle stream of purified nitrogen, to a final volume of about 300 μL. An internal standard (benzyl benzoate, 2 μg/sample) was added immediately before gas chromatography−mass spectrometry (GC-MS) analysis. The detailed operating conditions for the GC-MS are shown in section S1 in the Supporting Information (SI). QA/QC. Skin wipe efficiency has been evaluated. Details are provided in section S2 in the SI. Briefly, the wipe efficiencies for the first wipe were 82 ± 4%, 83 ± 4%, and 83 ± 4% (mean ± standard deviation (SD)) for DiBP, DnBP, and DEHP, respectively. The second wipe typically removed an additional 15% of the targeted phthalate, while the third wipe typically removed less than an additional 5%. Extraction recoveries for DEP-d4, DiBP-d4 and DEHP-d4 averaged 79 ± 9%, 85 ± 9%, and 83 ± 7% (mean ± SD), respectively. Samples with recovery rates less than 50% were excluded from further statistical analysis. DMP, DEP, DnBP, DiBP, and DEHP were detected in field blanks and averaged 0.21 ± 0.09, 0.04 ± 0.02, 0.49 ± 0.26, 0.42 ± 0.15, and 1.02 ± 0.44 μg (mean ± SD), respectively. Reported levels have been adjusted by subtracting the average mass in the blank normalized by skin surface area. The extraction recovery rates of DEP-d4, DiBP-d4, and DEHP-d4 have been used for adjusting the levels of DMP and DEP, DiBP
and develop effective mitigation strategies. One approach that can enhance our understanding of dermal exposure to phthalates is measuring the levels of phthalates at the skin surface by wiping the skin in a defined manner with solvent moistened gauze pads (i.e., skin wipes as described by Morgan et al.36). The levels of various chemicals in skin wipes can provide information on dermal exposure from the surrounding environment as a consequence of contact with contaminated surfaces, direct absorption from air, and particle deposition. The chemicals identified in skin wipes can enter our bodies through subsequent dermal absorption or through hand-tomouth contact (e.g., nail biting, smoking, and thumb and finger sucking).37 However, to date, only a few studies have examined phthalates in skin wipes.36,38,39 Furthermore, we are aware of no studies that have examined the variation of phthalate levels at different body locations or the temporal variation in skin wipe levels. Such information would enable not only better understanding and estimates of exposure via the dermal pathway but would also contribute to better standardized methods for the collection and analysis of skin wipes.40 Another area that has received little attention is the impact of handwashing on phthalate skin levels, although studies have shown that hand-washing can decrease exposures to nicotine and polybrominated diphenyl ethers (PBDEs).41,42 The primary objectives of the present study were to determine the skin surface levels (mass per unit area, μg/m2) of six commonly used phthalates (DMP, DEP, DiBP, DBP, BBzP, and DEHP) and to examine factors that might influence the skin surface levels, including body location, time of sampling, and hand-washing. The secondary objective was to use the results to estimate dermal absorption and to compare the estimates with those of uptake via other pathways. Such comparisons should improve understanding regarding the potential significance of the dermal pathway for overall human exposure to phthalates and thus aid in developing effective exposure control strategies.
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MATERIALS AND METHODS Study Design and Wipe Collection. Fudan University’s institutional review board approved the study protocol prior to collection of all skin wipe samples (IRB00002408 and FWA00002399). Ten male and ten female subjects were enrolled from the students and staff in the Department of Building Science, Tsinghua University. Participants were required to have no skin diseases and asked to sign a consent form and fill out a short questionnaire regarding age, height, weight, and daily activities. All participants were asked to not use any skincare products from rising in the morning until sampling in the afternoon, to not wash the skin wipe locations at least 4 h prior to sampling, and to try to stay in the same building until sampling. The wipe procedure was similar to the process described in a U.S. EPA study.36 Briefly, gauze pads (8 cm × 8 cm) were precleaned with dichloromethane (DCM) for 4 h using Soxhlet extraction, dried in a vacuum desiccator, wetted with 5 mL of isopropanol, and then stored in a 60 mL precleaned brown glass jar. All samples were collected at the laboratory by a single investigator to avoid between-investigator variability. The gauze pad was folded in half and first wiped over the skin surface two times using the two clean surfaces of the gauze pad. Then, it was refolded to expose the other two clean surfaces, and the skin surface was wiped two additional times. Hence, the 7429
dx.doi.org/10.1021/es501700u | Environ. Sci. Technol. 2014, 48, 7428−7435
Environmental Science & Technology
Article
Table 1. Phthalate Levels (μg/m2) and Frequency (%) of Occurrence in Skin Wipes Collected from 20 Subjects (10 Males and 10 Females)a compound
forehead
left forearm
right forearm
left back-of-hand
right back-of-hand
left palm
right palm
DiBP 50th %tile 75th %tile 95th %tile mean range frequency
437 73 nd−452 25
40 54 98 43 nd−98 83
39 54 118 43 nd−119 80
78 97 408 97 nd−408 84
72 112 265 79 nd−272 65
112 315 947 197 nd−947 85
69 249 860 190 nd−860 74
50th %tile 75th %tile 95th %tile mean range frequency
34 333 55 nd−342 30
61 94 143 68 30−143 100
57 86 235 70 18−240 100
108 158 390 124 38−390 100
100 160 302 122 nd−305 95
153 595 1865 403 32−1865 100
144 430 1385 340 41−1385 100
50th %tile 75th %tile 95th %tile mean range frequency
612 1050 1445 678 200−1445 100
745 1145 1825 867 316−1825 100
689 1065 2100 884 437−2110 100
1800 2400 3165 1840 612−3165 100
1520 2375 3175 1725 566-3180 100
2900 4910 12 900 4105 791−12900 100
3160 5015 10 200 4155 922−10200 100
DnBP
DEHP
a
Note: One left back-of-hand sample and two left forearm samples were lost. One left palm and one right palm sample were excluded from statistical analysis since their extraction recovery rates were less than 50%. nd = not detected.
Table 2. Geometric Means (95% CI) for the Ratios of Phthalate Levels at Different Body Locationsa compound
palm/back-of -hand
palm/forearm
palm/forehead
back-of-hand/forearm
back-of-hand/forehead
forearm/forehead
DiBP DnBP DEHP
1.7 (1.0−2.7) 2.0 (1.3−3.2) 2.0 (1.4−2.8)
3.4 (2.0−5.6) 3.4 (1.9−6.0) 4.0 (2.6−6.1)
b b 5.6 (3.3−9.7)
2.0 (1.4−3.0) 1.6 (1.3−2.2) 2.0 (1.6−2.5)
b b 2.8 (1.9−4.2)
b b 1.4 (0.9−2.1)
a Ratios were calculated for each subject, and then the geometric mean was calculated. The 95% confidence interval (CI) was back-calculated from the log-transformed data. bRatios that include DiBP and DnBP on the forehead are not reported due to their low detection frequency (
