Dermal Cytotoxicity

MWNTs were found to be cytotoxic in human skin fibroblasts (HSF42) and human epidermal keratinocytes (HEK) [42-44], whereas SWNTs were toxic in human keratinocyte (HaCaT) cultures [25, 26, 45]. Reduced cell proliferation and oxidative stress were reported also in epithelial (HeLa) cells [45] and murine epidermal cells (JB6 P + ) [46] upon incubation with SWNTs. 

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Dermal cytotoxicity SWNTs Arc discharge A549 Catalysts worsen cytotoxicity [53]... 

Pereira, E.M. et al., Tabebuia avellanedae naphthoquinones activity against methi-cillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis, Ann. Clin. Microbiol. Antimicrob., 22, 5, 2006. 

Although vesicants do not produce the same type of dermal damage in animals as they do in humans, they are still susceptible to the cytotoxic and systemic toxicities of these agents. 

Solubility/miscibility Soluble in water, ethanol, acetone, ether Biological considerations Oral LD50 (rats) = 17.9 ml kg. Repeated dermal exposure can defat skin. Repeated oral exposure can produce corneal opacities. Not cytotoxic to cells in primary culture. Intraperitoneal LD50 (mice) = 11.6 ml kg-1... 

The final type of chemical toxicity that will be presented are the vesicants, chemicals that cause blisters on the skin. There are two classes of blisters that implicate different mechanisms of vesication. Intraepidermal blisters are usually formed due to the loss of intercellular attachment caused by cytotoxicity or cell death. The second class occurs within the epidermal-dermal junction (EDJ) due to chemical-induced defects in the basement membrane components. The classic chemical associated with EDJ blisters is the chemical warfare agent sulfur mustard (bis-2-chloroethyl sulfide HD). HD is a bifunctional alkylating agent that is highly reactive with many biological macromolecules, especially those containing nucleophilic groups such as DNA and proteins. 

The ability of the trichothecenes to produce dermal toxicity is rather unusual for toxins. While only the more potent trichothecene mycotoxins have this effect, the cytotoxicity produced on contact with feed may result in lesions on the snout, muzzle, lips, and tongue of animals. Similar dermal effects have been reported in humans and in swine following topical application of T-2 toxin. T-2 toxin, DAS,... 

The cytotoxicity of acetaminophen has been demonstrated in cultures of HeLa cells, L929 and 3T3 murine fibroblasts, chick embryo neurons, rat embryonic and skeletal muscle, peripheral blood lymphocytes, and lung and dermal cells. In addition cytotoxicity of acetaminophen has been evaluated in BF-2 fish cell line (see section on Ecotoxicology ). 

Pathologic studies have demonstrated a perivascular, lymphocytic infiltrate with eosinophils in the dermis, fascia, and skeletal muscle, with variable numbers of eosinophils. The perivascular infiltrate was accompanied by thickening of the capillary and arteriolar endothelium in dermal, fascial, and muscle vessels. The frequent occurrence of microangiopathy (disease of the small blood vessels) in biopsy specimens suggests that ischemia (deficiency of blood supply) may contribute to tissue injury. Deposition of major basic protein (an eosinophil-specific protein) in affected tissue of some patients suggests that cytotoxic eosinophil degranulation products may also play a role in the pathogenesis of EMS. 

Although the correlation between low pHs (acids) and eye damage in the rabbit has not been found to be excellent, all alkalis (pH 11.5 or above) tested have been reported to produce opacities and ocular damage. Many laboratories now use pH cutoffs for testing of 2.0 or lower and 11.5 or 12.0 and higher. If a material falls outside these cutoffs (or is so identified due to other physicochemical parameters), then it is (1) not tested in the rabbit eye and is assumed to be corrosive (2) evaluated in a secondary screen such as an in vitro cytotoxicity test or primary dermal irritation test or (3) evaluated in a single rabbit before a full-scale eye irritation test is performed. It should be kept in mind that the correlation of all the... 

In vitro cytotoxicity tests that indicate basic cell toxicity by measuring parameters such as cell viability, proliferation, membrane damage, DNA synthesis, or metabolic effects have been used as indicators of dermal toxicity. 

The toxicity of formaldehyde is route-dependent. Irritation at the point of contact is seen by inhalation, oral, and dermal routes. High doses are cytotoxic and result in degeneration and necrosis of mucosal and epithelial cell layers. These observations are consistent with the hypothesis that toxic effects are mediated by formaldehyde itself and not by metabolites. No specific target molecule has been identified, although DNA-protein cross links have been identified (Casanova and Heck 1987). As discussed in... 

Sayes, C. M., Wahi, R., Kurian, P. A., Liu, Y, West, J. L., Ausman, K. D., Warheit, D. B., and Colvin, V. L. (2006). Correlating nanoscale titania structure with toxicity A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92, 174-185. 

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