Effects of Subchronic Dermal Application of Break-Free CLP® in CD-1 Mice

Abstract

ABSTRACTBreak-Free CLP® (Break-Free CLP) is a commercial metal cleaning, lubricating, and preserving compound used by the military, law enforcement agencies, and private citizens primarily for cleaning/maintenance of bore weapons. Break-Free CLP is predominantly polyalphaolefin oil, but it also contains dibasic ester, and isoparaffinic hydrocarbons, all of which have induced dermal irritation in laboratory animals. Studies were conducted to determine the biological effects of subchronic dermal application of Break-Free CLP to the clipped backs of CD-1 mice. Break-Free CLP, 2.5% croton oil (CO; positive control) or acetone (control vehicle) were applied neat, 50 μL/application, three times/week for 90 days. One 50-μL application to a 20 × 3 cm mouse dorsal skin surface area is roughly equivalent to human dermal contact with 260 μL of Break-Free CLP, assuming that contact with the material is primarily with the upper arms, forearms, and hands. Subchronic application of 2.5% CO in acetone (positive control) and Break-Free CLP resulted in gradual accumulation of a dermal irritation response over the 90-day study period. Foci of epithelial ulceration were evident in application site skin cross sections from Break-Free CLP- and CO-treated mice, with more cases of ulceration occurring in animals treated with CO (50 versus 20%). Genes involved in wound healing and skin defense pathways were also significantly affected by subchronic topical exposure to Break-Free CLP. Both alkaline phosphatase (ALKP) activity and the percentage of lymphocytes were significantly decreased for Break-Free CLP- and CO-treated animals, compared with their respective controls, suggesting systemic effects as a result of subchronic dermal application. Analysis of other major organs did not identify histopathology suggestive of toxicity, but dermal treatment with Break-Free CLP was associated with the down-regulation of a number of genes in the liver involved in stress response and metabolism. The results of this study support the manufacturer's recommendations that personal protective equipment (PPE) should be used with this product to prevent the development of chronic irritation as a result of repeat exposure.