Baynes R E, Halling K B, Riviere J E
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
Toxicol Appl Pharmacol. 1997 Jun;144(2):332-9. doi: 10.1006/taap.1997.8156.
Simultaneous exposure to DEET and permethrin was recently proposed to be associated with the "Gulf War Syndrome." However, no studies have reported the percutaneous absorption of DEET and permethrin when applied simultaneously to the skin as a mixture, the relevant route of exposure in the Persian Gulf. The present study quantitates percutaneous absorption of DEET and permethrin after coadministration to rodent and pig skin in vitro. Dosing solutions were also prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare vehicle effects on percutaneous absorption of permethrin and DEET. The influence of DEET on carbaryl absorption and dermal disposition was also assessed in pig studies to statistically demonstrate DEET effects in acetone or DMSO and different solvent concentrations. Topical application of permethrin + DEET resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2-1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a finding suggesting that DEET decreased permethrin absorption. DEET also inhibited carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures. Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was greater with DMSO and acetone than with ethanol in rat and mouse skin. These studies support DEET, but not permethrin or carbaryl, as having sufficient systemic exposure to potentially cause signs of toxicity when simultaneously applied with pesticides. Furthermore, these studies demonstrated that DEET does not necessarily enhance dermal absorption of all toxicants as was originally hypothesized.
最近有人提出,同时接触避蚊胺和氯菊酯与“海湾战争综合征”有关。然而,尚无研究报告将避蚊胺和氯菊酯作为混合物同时涂抹于皮肤上时的经皮吸收情况,而这是在波斯湾地区相关的接触途径。本研究对避蚊胺和氯菊酯共同施用于啮齿动物和猪皮肤后的经皮吸收情况进行了定量分析。还分别用丙酮、二甲基亚砜(DMSO)或乙醇配制了给药溶液,以比较溶媒对氯菊酯和避蚊胺经皮吸收的影响。在猪的研究中还评估了避蚊胺对西维因吸收和皮肤分布的影响,以从统计学上证明避蚊胺在丙酮或DMSO以及不同溶剂浓度下的作用。局部涂抹氯菊酯+避蚊胺后,避蚊胺被吸收(剂量的1 - 20%),但氯菊酯未被吸收。仅在小鼠皮肤单独涂抹氯菊酯时检测到氯菊酯(剂量的1.2 - 1.7%),这一发现表明避蚊胺降低了氯菊酯的吸收。避蚊胺在丙酮混合物中也抑制了西维因的吸收,但对DMSO混合物没有影响。无论使用何种溶媒,避蚊胺均未增强西维因渗透进入皮肤的能力。对于避蚊胺,在小鼠皮肤中的吸收量(剂量的10.7 - 20.6%)大于大鼠皮肤(剂量的1.1 - 5.2%)和猪皮肤(剂量的2.8%)。在大鼠和小鼠皮肤中,避蚊胺在DMSO和丙酮中的吸收程度大于在乙醇中的吸收程度。这些研究表明,避蚊胺在与农药同时使用时,有足够的全身暴露量,可能导致毒性迹象,但氯菊酯或西维因并非如此。此外,这些研究表明,避蚊胺不一定如最初假设的那样会增强所有有毒物质的经皮吸收。