乙二醇乙醚醋酸酯（2-ethoxyethyl acetate, EEAc），由於其對水及油性物質有良好之溶解性，於印刷工業經常使用作為油墨之稀釋劑及清潔劑。作業場所中EEAc的暴露途徑為呼吸吸入及皮膚吸收，有研究已強調EEAc皮膚吸收之重要性及推論經皮吸收可能為主要之暴露途徑，然而，目前尚未有任何相關類似之研究探討職場員工之EEAc皮膚吸收情形，及缺乏作業現場皮膚暴露資料，而過去對於探討連續職業暴露EEAc下之生物偵測研究亦是寥寥可數。因此，本研究目的為：1.評估網版印刷業勞工EEAc之暴露情形及探討影響作業環境中EEAc皮膚暴露變異及皮膚吸收之潛在因子；2.探討空氣及皮膚暴露與尿中生物指標單乙氧基醋酸（2-ethoxyacetic acid, EAA）濃度之相關性；3.評估連續職業暴露EEAc下，尿中EAA是否有累積情形；4.評估職業暴露EEAc之尿中生物暴露指標之建議濃度值及採樣時序性；5.探討EEAc職業暴露終止後，暴露員工連續36小時尿中EAA之動力學特性。研究對象為20位職業暴露EEAc之員工，進行連續5個工作天的個人空氣及皮膚EEAc暴露偵測，並收集連續5個工作天的上下班前尿液樣本進行生物偵測，另有10位員工收集一周工作完下班後連續36小時之尿液樣本。

　　本研究結果發現：1.皮膚之EEAc暴露濃度值與空氣中EEAc濃度有良好的相關性（r>0.55），認為除了皮膚直接接觸溶劑會導致皮膚暴露以外，經由揮發的EEAc蒸氣亦為作業現場皮膚暴露的重要來源。2.皮膚暴露濃度由手掌至頸部依次遞減，以手掌暴露濃度最高為0.79μg/cm2，因此建議佩戴防護性良好之手套，可有效減少皮膚暴露。有使用手套者，其每單位EEAc空氣暴露濃度所產生尿中EAA之濃度值較未戴手套者顯著為低，推論EEAc暴露員工於現場作業是有顯著皮膚吸收EEAc之情形。3.現場EEAc暴露濃度相同時，皮膚流汗之勞工會有較高之EEAc暴露量及吸收量。4.上班前尿中EAA濃度值能反映出生物指標的累積現象，此累積現象可能來自於共同呼吸及皮膚吸收EEAc的結果。控制空氣濃度後尿中EAA濃度值隨工作日數增加仍有緩和的上升，推論主要是因皮膚暴露使得尿中生物指標有緩慢代謝出來的結果。5.上班前尿中EAA濃度值應以反映前2天或前3天之空氣中EEAc濃度值為最佳，以及下班前尿液中生物指標濃度值以反映前一天或前兩天之呼吸暴露量最佳，若考量生物偵測適當採樣時序，建議可在一工作週之第三或第四天以上下班前尿中EAA濃度值來評估先前之暴露濃度。6.暴露終止後，EAA濃度變化呈現雙峰或多峰之現象，推論是因EAA之半衰期較文獻上或本研究所推估之23.4小時為長，或之前現場EEAc暴露亦有雙峰或多峰之高暴露情形。

　　Due to its considerably hydrophilic and lipophilic properties, 2-ethoxyethyl acetate（EEAc）has been widely used as thinner and cleaner in printing industry. The main routes of occupational exposure to EEAc are via inhalation and skin, and several lines of evidences in literature suggest the dermal exposure could be more important than inhalation with respect to the body burden contribution. This conclusion, however, has not been confirmed in any studies performed in an actual occupational environment. Moreover, no any dermal exposure measurements have been conducted ever either in the field study. Thus, the purposes of this study are: 1. to investigate the exposure levels of EEAc via respiratory and dermal routes respectively in an actual occupational setting, and to evaluate the underlying factors affecting the variability of dermal EEAc exposure; 2. to investigate the relationship between exposure factors and urinary biomarker 2-ethoxyacetic acid (EAA), and the profile of urinary EAA concentrations with concurrent exposure via inhalation and skin; 3. to assess the accumulation of urinary EAA under the occupationally repeated exposure to EEAc; 4. to assess the appropriate sampling time and projected biological exposure index (BEI) value of urinary EAA; and 5. to explore the excretory kinetics of urinary EAA for the workers occupationally exposed to EEAc. Twenty EEAc-exposed workers, recruited from a printing shop, were performed with environmental monitoring and biological monitoring. We collected the respiratory, dermal EEAc exposure and urine samples from each subject during five consecutive workdays between W2~W6. Moreover, 10 workers from the twenty were further performed to evaluate excretory kinetic of urinary EAA from 36-hr consecutive urine samples.

　　We concluded that: 1. Evaporative EEAc could be an important source to both dermal and respiratory exposures to EEAc. Engineering control and/or wearing protective equipment should be performed at the priority to minimize the workers’ EEAc exposure. 2. Direct contact to EEAc could also increase the EEAc dermal exposure on palms (0.79μg/cm2). Therefore, wearing impermeable gloves during high-exposure tasks might effectively reduce dermal exposure. 3. The exposures to EEAc via lungs and skin were both job-dependent, suggesting high-risk jobs should be identified in the first priority with respect to exposure reduction. 4. We have demonstrated the dermal EEAc absorption was significant by significantly lower urinary EAA concentrations adjusted by airborne EEAc for those who wore gloves than those not. 5. Perspiration could enhance dermal absorption of EEAc in workplaces. 6. Body burden accumulation might result from concurrent respiratory and dermal EEAc absorption and/or the prolonged half-life of urinary EAA (23.4 hr). 7. It would be more appropriate to perform biomonitoring for EEAc exposure on the third or forth day in a workweek. We suggested 111 and 78 mg/g creatinine of EAA in urine as the BEI of occupational EEAc exposure for pre- and post-shift urine, respectively. 8. Bi-modal or multi-modal kinetic patterns, observed in 36-hr consecutive urine, could be due to longer half-life of estimate of 23.4 hr. A study with more subjects and a complete real-time EEAc exposure profile in kinetic exploration is warranted to lead a more affirmative conclusion.

American Conference of Governmental Industrial Hygienists（ACGIH）. TLVs &
BEIs: Threshold limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices for 2003. Cincinnati, OH. (2003)
Angerer J, Lichterbeck E, Begerow J, Jekel S, Lehnert G. Occupational chronic exposure to organic solvents. XIII. Glycolether exposure during the
production of varnishes. Int Arch Occup Environ Health 62:123-6 (1990)
Bucks DA, Maibach HI, Guy RH. Occulsion does not uniformly enhance penetration
in vivo,” In Bronaugh, R. L., Maibach, H. I.(ed) “Percutaneous
absorption. Mechanisms-methodology-drug delivery,” New York, Marcel
Dekker: 77-93 (1989)
Chang HY, Tsai CY, Lin YQ, Shih TS. Urinary biomarkers of occupational N,N-
dimethylformamide (DMF) exposure attributed to the dermal exposure.
J Exp Anal Environ Epidemiol 14: 214-221 (2004)
Chia SE, Foo SC, Khoo NY, Jeyaratnam J. Menstrual patterns of workers exposed
to low levels of 2-ethoxyethylacetate (EGEEA). Am J Ind Med 31:148-52
(1997)
Environmental Protective Agency. (EPA) Pesticide Assessment Guidelines for
Pesticides. Rev Environ Contam Toxicol 129: 79-93 (1987)
Doe JE. Ethylene glycol monethyl ether and ethylene glycol monethyl ether
acetate teratology studies. Environ Health Perspect 57:33-41 (1984)
Dugard PH, Walker M, Mawdsley SJ, Scott RC. Absorption of some glycol ethers
through human skin in vitro. Environ Health Perspect 57:193-7 (1984)
Dugard PH. Skin permeability theory in relation to measurements of
percutaneous absorption in toxicology,” In Marzulli, F. N., Maibach, H.
I.(ed) “Dermatotoxi-
cology,” Washington, Hemisphere : 95-120 (1987)
Ghanayem BI, Burka LT, Matthews HB. Structure-activity relationships for the
in vitro hematotoxicity of n-alkoxyacetic acids, the toxic metabolites
of glycol ethers. Chem Biol Interact 70:339-352 (1989)
Goodman M, Barry BW. “Action of penetration enhancers on human stratum
corneum as assessed by differential scanning calorimetry,” In Bronaugh,
R. L., Maibach, H. I.(ed) “Percutaneous absorption. Mechanisms-
methodology-drug delivery,” New York, Marcel Dekker: 567-93 (1989)
Groeseneken D, Veulemans H, Masschelein R. Urinary excretion of ethoxyacetic
acid after experimental human exposure to ethylene glycol monoethyl
ether. Br J Ind Med 43: 615-619 (1986)
Groeseneken D, Veulemans H, Masschelein R, Van Vlem E. Pulmonary absorption
and elimination of ethylene glycol monoethyl ether acetate in man. Br J
Ind Med 44:309-316 (1987a)
Groeseneken D, Veulemans H, Masschelein R, Van Vlem E. Ethoxyacetic acid: a
metabolite of ethylene glycol monoethyl ether acetate in man. Br J Ind
Med 44: 488-493 (1987b)
Hardin BD, Bond GP, Sikov MR, Andrew FD, Beliles RP, Niemeier RW. Testing of
selected workplace chemicals for teratogenic potential. Scand J Work
Environ Health 7:66-75 (1981)
Johanson G. Aspects of biological monitoring of exposure to glycol ethers.
Toxicol Lett 43:5-21 (1988a)
Johanson G, Dynesius B. Liquid/air partition coefficients of six commonly
used glycol ethers. Br J In Med 45:561-564 (1988b)
Johanson G, Boman A. Percutaneous absorption of 2-butoxyethanol vapour in
human subjects. Br J In Med 48:788-792 (1991)
Jonsson K, Pedersen J, Steen G. Ethoxyacetic acid and N-ethoxyacetylglycine:
metabolites of ethoxyethanol (ethylcellosolve) in rats. Acta Pharmacol
Toxicol 50:358-362 (1982)
Kim Y, Lee N, Sakai T, Kim KS, Yang JS, Park S, Lee CR, Cheong HK, Moon Y.
Evaluation of exposure to ethylene glycol monoethyl ether acetates and
their possible haematological effects on shipyard painters. Occup Envron
Med 56:378-82 (1999)
Lin CK, Chen RY. Survey of glycol ether use in Taiwan, 1991. Am J Ind Med
24:101-8 (1993)
Loh CH, Shih TS, Liou SH, Lin YC, Hsieh AT, Chen CY, Liao GD. Haematological
effects among silk screening workers exposed to 2-ethoxy ethyl acetate.
Occup Environ Med 60:E7 (2003)
Lowry LK, Stumpp DA, Orbaugh C, Rieders F. Applications of biological
monitoring in occupational health practice: practical application of
urinary 2-ethoxyacetic acid to assess exposure to 2-ethoxyethyl acetate
in large format silk-screening operations. Int Arch Occup Environ Health
65:S47-51 (1993)
Nagano K, Nakayama W, Koyano M, Oobayashi H, Adachi H, Yamada T. Mouse
testicular atrophy induced by ethylene glycol monoalkyl ethers. Jap J
Ind Health 21:29-35 (1979)
Nakaaki K, Fukabori S, Tada O. An experimental study on percutaneous
absorption of some organic solvents. J Sci Labour 56:1-9 (1980)
NIOSH. Criteria for a recommended standard : occupational exposure to ethylene
glycol monomethyl ether, ethylene glycol monoethyl ether and their
acetates. US Department of Health and Human Service. Centers for Disease
Control, National Institute for Occupational Safety and Health (1991)
Rosenberg J, Rempel D. Biological monitoring. Occup Med 5: 491-498 (1990)
Ryan LW, Linda SA, Robert IK. Perspiration increased human pesticide
absorption following surface contact during an indoor scripted activity
program. J Exp Anal Environ Epidemiol 14:129-36 (2004)
Schneider T, Cherrie JW, Vermeulen R, Kromhout H. Dermal exposure
assessment. Annal Occup Hygiene 44:493-499 (2000)
Shih TS, Chen CY, Chou JS. Exposure assessment of 2-ethoxy ethyl acetate in
silk-screening industry. IOSH902-A307. Taipei, Taiwan: Institute of
Occupational Safety and Health. (2001)
Smallwood A, Debord K, Burg J, Mosley C, Lowry L. Determination of urinary
2-ethoxyacetic acid as an indicator of occupational exposure to 2-ethoxy-
ethanol. Appl Ind Hyg 3: 47-50 (1988)
Veulemans H, Groeseneken D, Masschelein R, Van Vlem E. Field study of the
urinary excretion of ethoxyacetic acid during repeated daily exposure to
the ethyl ether of ethylene glycol and the ethyl ether of ethylene glycol
acetate. Scand J Work Environ Health 13: 239-242 (1987)
Vincent R, Poirot P, Subra I, Rieger B, Cicolella A. Occupational exposure to
organic solvents during paint stripping and painting operations in the
aeronautical industry. Int Arch Occup Environ Health 65:377-80 (1994)
Welch LS, Cullen MR. Effect of exposure to ethylene glycol ethers on shipyard
painters: III. Hematologic effects. Am J Ind Med 14:527-36 (1988)