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体外大鼠皮肤对乙酸苄酯的经皮吸收。3. 与人体皮肤的比较。

Percutaneous absorption of benzyl acetate through rat skin in vitro. 3. A comparison with human skin.

作者信息

Garnett A, Hotchkiss S A, Caldwell J

机构信息

Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, Imperial College of Science Technology and Medicine, London, UK.

出版信息

Food Chem Toxicol. 1994 Nov;32(11):1061-5. doi: 10.1016/0278-6915(94)90147-3.

Abstract

The comparative absorption of the fragrance and industrial compound, benzyl acetate, has been studied in rat and human skin, using shaved, full-thickness dorsal skin of male Fischer 344 rats and full-thickness human skin obtained from patients undergoing surgical resection. Penetration of the compound through rat and human skin was evaluated in vitro in flow-through diffusion cells following topical application of neat [methylene-14C] benzyl acetate (33.1 mg/cm2) to the epidermal surface and occlusion with a teflon cap, 2.9 cm above the skin surface. The absorption of benzyl acetate across rat skin was rapid and extensive, reaching 34.3 +/- 3.9% of the applied dose (11.3 +/- 1.3 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 55.8 +/- 5.0% of the applied dose (18.5 +/- 1.7 mg/cm2) at 72 hr. The penetration of benzyl acetate was significantly (P < 0.05) less rapid and extensive through human skin, reaching 5.5 +/- 0.1% of the applied dose (1.8 +/- 0.0 mg/cm2) (mean +/- SD, n = 12) at 24 hr and 17.8 +/- 3.3% of the applied dose (5.9 +/- 1.1 mg/cm2) at 72 hr. The rate of penetration of benzyl acetate was greater through rat skin than through human tissue at all time points studied up to 72 hr. The maximum rate of skin penetration was 0.6 +/- 0.1 mg/cm2/hr and 0.1 +/- 0.0 mg/cm2/hr through rat and human skin, respectively. These data indicate that systemic exposure to benzyl acetate may occur after skin contact in humans. They also support the evidence from the literature that human skin is generally less permeable to xenobiotics than rat skin.

摘要

已使用雄性Fischer 344大鼠剃毛后的全层背部皮肤以及从接受手术切除的患者身上获取的全层人体皮肤,对香料及工业化合物乙酸苄酯在大鼠和人体皮肤中的吸收情况进行了研究。在体外流通扩散池中,将纯的[亚甲基 - 14C]乙酸苄酯(33.1 mg/cm²)局部涂抹于表皮表面,并用聚四氟乙烯帽封闭,该帽位于皮肤表面上方2.9 cm处,以此评估该化合物在大鼠和人体皮肤中的渗透情况。乙酸苄酯在大鼠皮肤中的吸收迅速且广泛,在24小时时达到给药剂量的34.3 ± 3.9%(11.3 ± 1.3 mg/cm²)(均值 ± 标准差,n = 12),在72小时时达到给药剂量的55.8 ± 5.0%(18.5 ± 1.7 mg/cm²)。乙酸苄酯通过人体皮肤的渗透速度明显较慢且程度较低(P < 0.05),在24小时时达到给药剂量的5.5 ± 0.1%(1.8 ± 0.0 mg/cm²)(均值 ± 标准差,n = 12),在72小时时达到给药剂量的17.8 ± 3.3%(5.9 ± 1.1 mg/cm²)。在研究的长达72小时的所有时间点,乙酸苄酯通过大鼠皮肤的渗透速率均高于通过人体组织的渗透速率。通过大鼠和人体皮肤的最大皮肤渗透速率分别为0.6 ± 0.1 mg/cm²/小时和0.1 ± 0.0 mg/cm²/小时。这些数据表明,人体皮肤接触乙酸苄酯后可能会发生全身暴露。它们还支持了文献中的证据,即人体皮肤对外源化学物质的通透性通常低于大鼠皮肤。

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