Qiao G L, Chang S K, Riviere J E
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Toxicol Appl Pharmacol. 1993 Sep;122(1):131-8. doi: 10.1006/taap.1993.1180.
The effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of total 14C were investigated following topical application of 2,6-[ring-14C]parathion onto four skin sites (300 micrograms/10 microCi; 40 micrograms/cm2) in weanling swine using occluded and nonoccluded dosing systems. The excretion profile was examined after iv administration. After dosing onto the abdomen, buttocks, back, and shoulder (N = 4/site), total urinary and fecal excretion (%dose) by 168 hr were, for the occluded system, 43.94 +/- 2.24, 48.47 +/- 7.85, 48.82 +/- 4.49, and 29.28 +/- 5.70%, and for the nonoccluded system, 7.47 +/- 2.16, 15.60 +/- 3.71, 25.00 +/- 8.75, and 17.41 +/- 1.76%, respectively. After iv dosing, 98.44 +/- 2.83% of the applied dose was excreted primarily via urine. The total recoveries for different sites ranged from 90.09 +/- 7.10 to 94.62 +/- 1.98% in the occluded system, 77.84 +/- 5.75 to 88.18 +/- 3.34% in the nonoccluded system, and 99.03 +/- 2.89% in the iv experiments. Time of maximal excretion rate was determined in the occluded system as abdomen (7.9 +/- 3.6 hr) < buttocks (9.4 +/- 2.6 hr) < shoulder (10.5 +/- 3.8 hr) < back (13.3 +/- 7.7 hr), but in the nonoccluded system as buttocks (11.9 +/- 3.6 hr) < shoulder (12.6 +/- 4.1 hr) < back (14.3 +/- 6.4 hr) < abdomen (16.9 +/- 7.1 hr). The percutaneous absorption from the shoulder was much lower than that from the other three sites under occluded conditions. However, if nonoccluded dosing was employed, absorption from the abdomen became the lowest, with shoulder and buttocks being similar, and the back the highest. Occlusion conceals the site difference and enhances both the extent and the rate of parathion percutaneous absorption in vivo. 14C residue pattern in tissues and dosing materials was site and dosing method dependent, all of which are factors which must be considered when assessing the risk of exposure to topically applied compounds.
在断奶仔猪的四个皮肤部位(300微克/10微居里;40微克/平方厘米)局部应用2,6-[环-14C]对硫磷,使用封闭和非封闭给药系统,研究了解剖部位和封闭对总14C经皮吸收和残留模式的影响。静脉注射给药后检查排泄情况。在腹部、臀部、背部和肩部给药后(每个部位N = 4),对于封闭系统,到168小时时,尿和粪便的总排泄量(%剂量)分别为43.94±2.24%、48.47±7.85%、48.82±4.49%和29.28±5.70%;对于非封闭系统,分别为7.47±2.16%、15.60±3.71%、25.00±8.75%和17.41±1.76%。静脉注射给药后,98.44±2.83%的给药剂量主要通过尿液排泄。在封闭系统中,不同部位的总回收率在90.09±7.10%至94.62±1.98%之间;在非封闭系统中,为77.84±5.75%至88.18±3.34%;在静脉注射实验中为99.03±2.89%。在封闭系统中确定最大排泄率的时间为腹部(7.9±3.6小时)<臀部(9.4±2.6小时)<肩部(10.5±3.8小时)<背部(13.3±7.7小时),但在非封闭系统中为臀部(11.9±3.6小时)<肩部(12.6±4.1小时)<背部(14.3±6.4小时)<腹部(16.9±7.1小时)。在封闭条件下,肩部的经皮吸收远低于其他三个部位。然而,如果采用非封闭给药,则腹部的吸收最低,肩部和臀部相似,背部最高。封闭掩盖了部位差异,增强了对硫磷在体内的经皮吸收程度和速率。组织和给药材料中的14C残留模式取决于部位和给药方法,所有这些都是在评估局部应用化合物暴露风险时必须考虑的因素。