Gerhart J M, Hatoum N S, Halder C A, Warne T M, Schmitt S L
IIT Research Institute, Life Sciences Research, Chicago, Illinois.
Fundam Appl Toxicol. 1988 Jul;11(1):76-90. doi: 10.1016/0272-0590(88)90272-2.
A furnace oil, a dewaxed heavy paraffinic distillate, and a solvent-extracted lubricant base oil induced skin tumors in 9/43, 26/48, and 1/47 male C3H mice, respectively, during lifetime skin-painting bioassays. An initiation/promotion (I/P) bioassay was conducted to assess the I/P potential of these materials. During a 28-week initiation bioassay, groups of 30 male CD-1 mice were first treated dermally once daily for 5 days with 25 or 50 microliter of test materials or 50 microliter of acetone, rested for 2 weeks, then treated twice per week for 25 weeks with 50 microliter (0.1 mg/ml) phorbol-12-myristate-13-acetate (PMA). Only groups treated with the heavy paraffinic distillate had a significantly higher incidence of papillomas relative to the acetone control group. During a 28-week promotion bioassay, groups of 30 male CD-1 mice were treated once with 50 microliter of either DMBA (1.0 mg/ml) or acetone, rested for 2 weeks, and then treated twice per week with test material for the remaining 25 weeks. The furnace oil and dewaxed heavy paraffinic distillate showed significantly higher incidences of carcinomas and papillomas in DMBA-initiated mice relative to their acetone-initiated controls. Together these bioassay data suggest that only the dewaxed heavy paraffinic distillate is a complete carcinogen, having both initiating and promoting activity; furnace oil is a promoter only, while the solvent-extracted lubricating oil is noncarcinogenic. Overall, the I/P bioassay correlated well with the results of the lifetime skin-painting bioassay.
在终生皮肤涂抹生物测定中,一种炉用油、一种脱蜡重质石蜡馏出物和一种溶剂萃取润滑油基础油分别在9/43、26/48和1/47的雄性C3H小鼠中诱发了皮肤肿瘤。进行了一项启动/促进(I/P)生物测定以评估这些物质的I/P潜力。在为期28周的启动生物测定中,每组30只雄性CD-1小鼠首先每天经皮处理一次,连续5天,分别给予25或50微升测试物质或50微升丙酮,休息2周,然后每周两次,连续25周给予50微升(0.1毫克/毫升)佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)。只有用重质石蜡馏出物处理的组相对于丙酮对照组有显著更高的乳头状瘤发生率。在为期28周的促进生物测定中,每组30只雄性CD-1小鼠用50微升二甲基苯并蒽(DMBA,1.0毫克/毫升)或丙酮处理一次,休息2周,然后在剩余的25周内每周两次用测试物质处理。相对于其丙酮启动的对照组,炉用油和脱蜡重质石蜡馏出物在DMBA启动的小鼠中显示出显著更高的癌和乳头状瘤发生率。这些生物测定数据共同表明,只有脱蜡重质石蜡馏出物是一种完全致癌物,具有启动和促进活性;炉用油只是一种促进剂,而溶剂萃取润滑油是非致癌的。总体而言,I/P生物测定与终生皮肤涂抹生物测定的结果相关性良好。