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Antioxidant defense and toxic effects of occupational chemicals to skin.

Murray-AR; Kisin-E; Castranova-V; Kommineni-C; Shvedova-AA
Toxicologist 2006 Mar; 90(1):172
A variety of compounds used in industry, such as cumene hydroperoxide (Cum- OOH), phenol (PhOH), and metal working fluids (MWFs), are toxic to the skin and can result in inflammation, allergic and contact dermatitis, and/or cancer promotion. The mechanisms for this toxicity are largely unknown. We hypothesize that free radical production with the attendant loss of antioxidant protection and the development of oxidative stress are key contributors to dermal toxicity. In vivo experiments revealed the formation of -phenyl-N-tert-butylnitrone spin-trapped radical adducts in the skin of mice exposed to PhOH or Cum-OOH. Depletion of glutathione (GSH; pretreatment with DL-buthionine sulfoximine) prior to phenol exposure resulted in the production of significantly more radicals than in animals exposed to phenol alone. Similar results were obtained from animals given a vitamin E deficient diet for 20 weeks prior to dermal exposure to Cum-OOH. Mice maintained on a diet deficient in vitamin E and exposed to Cum-OOH had significantly higher rates of radical formation compared to the mice given a diet with a sufficient amount of vitamin E. Exposure to PhOH, Cum-OOH, or MWFs also resulted in reduction of antioxidant defense (oxidation of GSH and protein thiols, and decreased levels of vitamin E and total antioxidant reserves) in the mouse skin. Histologic evaluation after exposure to PhOH, Cum-OOH, or MWF revealed increased dermal inflammation when the above chemicals were applied to the skin of mice with pre-existing oxidative stress. In conclusion, impairment of antioxidant skin defense contributed to increased inflammation indicating the essential role of the latter against free radical skin damage. Antioxidant status is an important factor in determining the susceptibility to skin damage resulting from exposure to occupational chemicals.
Antioxidation; Antioxidants; Toxins; Toxic-effects; Occupational-exposure; Chemical-burns; Chemical-reactions; Phenols; Metalworking-fluids; Skin; Skin-cancer; Skin-disorders; Skin-irritants; Allergic-dermatitis; Dermatitis; Cancer; Dermatosis; In-vivo-studies; Laboratory-animals; Animals; Animal-studies
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NIOSH Division
Priority Area
Work Environment and Workforce: Emerging Technologies
Source Name
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California