經皮吸收已成為職場作業人員有害物質進入體內重要的暴露途徑之一，而經皮吸收速率之高低與皮膚完整性有關。皮膚的特殊結構可保護身體不受外來刺激之侵害，並維持身體的恆定，這些功能統稱為皮膚障壁功能。以往研究顯示皮膚障壁功能損害將導致皮膚吸收量明顯升高。皮膚疾病亦會對皮膚障壁功能產生直接的影響，因此皮膚狀態對於職業現場作業員工危害物之暴露與健康評估相當重要。二硫化碳(carbon disulfide, CS2)因其脂溶性佳與低沸點之特性，長久以來廣泛使用於工業界與化學實驗分析。CS2除可經由呼吸道進入人體外，皮膚暴露於CS2溶液中亦有可能造成皮膚吸收。縲縈絲製造業為工業界中CS2使用量最大者，對於縲縈絲製造過程中作業員工皮膚暴露於CS2的情形下，是否造成皮膚疾病與皮膚障壁功能損害並無文獻資料，而以上兩者皆可能會進一步影響CS2經皮吸收的能力。本研究以實際職場研究為起點，探討縲縈絲作業員工CS2皮膚暴露對皮膚疾病，皮膚障壁功能，與CS2內在暴露劑量之影響，並進一步以動物實驗探討CS2皮膚暴露與皮膚障壁功能之劑量-效應關係與障壁功能破壞之機制。本研究以實際CS2暴露之縲縈絲工廠員工為研究對象，進行員工之皮膚疾病診斷與皮膚障壁功能量測，並以尿中2-thiothiazolidine-4-carboxylic acid(TTCA)作為CS2內在暴露劑量評估指標，進行包括皮膚健康狀態之個人工作衛生習慣及健康情況之分析。另外以實驗條件良好控制下之裸鼠動物模式進行不同濃度CS2之皮膚暴露，並以經皮水分散失(transepidermal water loss, TEWL)量測、皮膚病理切片分析、與皮膚脂肪成分分析進行針對皮膚障壁功能破壞機制探討。職場研究結果發現縲縈絲廠作業員工為手部皮膚疾病發生之高危險族群，單獨暴露CS2即可顯著增加縲縈絲廠作業員工手部皮膚疾病的盛行率危險比。縲縈絲廠作業員工可能會因皮膚疾病而導致體內CS2內在暴露劑量顯著之增加。另一方面，縲縈絲工廠作業員工皮膚在長期且重複性的CS2暴露下可造成皮膚障壁功能之異常，且皮膚障壁功能損失趨勢可分為兩個階段，分別代表淺層與深層角質層所提供之皮膚障壁功能。比較暴露於CS2中之作業員工與未暴露之控制組之結果，員工淺層的角質層可能仍有障壁功能之保護效果，但深層的角質層卻可能有較嚴重之破壞情形，此假說尚須進一步更完整的實驗設計來證實。實驗室裸鼠實驗結果發現TEWL值上升、皮膚障壁功能回復率、與角質層脂肪之萃取量均與CS2之皮膚暴露濃度呈現劑量-效應之關係。角質層脂肪的萃取與活性表皮層細胞的死亡可能為CS2導致之皮膚障壁功能損害兩個主要機制。綜合以上之發現，可知皮膚疾病對於縲縈絲廠CS2暴露之作業員工內在暴露劑量為主要影響因素之一，且皮膚暴露於CS2為員工手部皮膚疾病發生的主因。CS2導致之皮膚障壁功能損害主要機制可能為角質層脂肪的萃取與活性表皮層細胞的死亡。對於職場可能暴露CS2之員工包括皮膚疾病與皮膚障壁功能等之皮膚健康情形必須加以注意，以減少職場中有害物質經由皮膚吸收而增加暴露員工健康風險。

Skin absorption is one of the most important routes of exposure in occupational environment. Skin barrier function provides substantial protection for the humans from the environmental hazards via dermal exposure. A great number of studies have demonstrated that skin barrier function is associated with the skin absorption potential and any pathological changes in skin could result in the damage to skin barrier function. Carbon disulfide (CS2) has been widely used as a solvent in the manufacturing processes and in the laboratory chemical analysis because of its high lipophilicity and lower boiling point. Very limited studies, however, have explored its potency causing skin disease, skin barrier function alteration, and the relationship between skin absorption and barrier destruction after topical exposure to CS2. Based on the observation results from real occupational settings, the objectives of this study were to investigate the prevalence of skin disease and to estimate the skin barrier function alteration among rayon manufacturing workers. Moreover, this study also tried to determine the effects of personal factors on the relationship between CS2 exposure and urinary 2-thiothiazolidine-4-carboxylic acid (TTCA), an estimate of the internal dose of CS2 exposure. Finally, we used animal model of nude mouse to determine whether there are dose-response relations of skin barrier function perturbation, pathological alteration, and intercellular lipid analysis of stratum corneum to topical exposure at various levels of CS2. The results showed a considerably elevated prevalence of skin disease was observed among rayon manufacturing workers and occupational hand dermatitis could occur resulting from occupational exposure to CS2 alone. The personal factor like host’s skin disease was found to possibly affect the relations of U-TTCA to the occupational exposure to CS2. Moreover, the occupational exposure to CS2 could result in the perturbation of the skin barrier function. Basal transepidermal water loss (TEWL) might be a sensitive indicator to chronic and repeated skin exposure to CS2. Two-stage increasing pattern was found in the TEWL elevation profile after sequential tape-stripping on skin of rayon workers and controls and the results showed less steep increase in the first linear stage but more rapid increase in the second linear stage in workers comparing with controls. This finding hypothesized that CS2 exposure could result in more resistance to the perturbation in the superficial stratum corneum layers but more serious damage to the deeper stratum corneum layers. This hypothesis, however, warrants a more through study to affirm. The results from animal study revealed clear dose-response fashions between skin barrier perturbation, barrier recovery rate, and amounts of lipid extraction after various CS2 exposures. Two mechanistic pathways were raised to account for CS2-induced epidermal alterations: intercellular lipid depletion and keratinocyte damage. In summary, skin health problem is a noteworthy factor in the consideration of health concern among rayon manufacturing workers. The skin exposure to CS2 for those who have skin problems on the sites possibly or potentially exposed to CS2 in the occupational environment should take effective actions in reducing skin exposure.

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