Sulfur mustards models

Considering all the above data, the U.S. EPA (1991) selected the unit risk of 8.5 x 10 per pg/m, derived from the Weibull time-to-tumor model, as the recommended upper bound estimate of the carcinogenic potency of sulfur mustard for a lifetime exposure to HD vapors. However, U.S. EPA (1991) stated that "depending on the unknown true shape of the dose-response curve at low doses, actual risks may be anywhere from this upper bound down to zero". The Weibull model was considered to be the most suitable because the exposures used were long-term, the effect of killing the test animals before a full lifetime was adjusted for, and the sample size was the largest obtainable from the McNamara et al. (1975) data. 

ATSDR (2008). ToxFAQs for nerve agents. Retrieved May 5, 2008 from http //www.atsdr.cdc.gov/tfactsl66.html Babin, M.C., Ricketts, K. (2000). Systemic administration of candidate antivesicants to protect against topically applied sulfur mustard in the mouse ear vesicant model (MEVM). J. Appl. Toxicol. 20, Suppl. 1 S141-4. 

Bossone, C., Newkirk, K., Schulz, S., Railer, R., Gazaway, M., Shutz, M., Clarkson, E., Estep, S., Subramarian, P., Castro, A. Clinkscales, J., Lukey, B. (2002). Effects of prednisolone acetate on ocular sulfur mustard injury in a rabbit model. Technical report, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, 1-22. 

Smith, W.J., Gross, C.L., Chan, P., Meier, H.L. (1990). The use of human epidermal keratinocytes in cultures as a model for studying sulfur mustard toxicity. Cell Biol. Toxicol. 6 285-91. 

Babin, M.C., Ricketts, K.M. et al. (2003). A 7-day mouse model to assess protection from sulfur mustard (SM) skin injury. J. Toxicol. Cutan. Ocul. Toxicol. 22(4) 231-42. 

Casillas, R.P., Mitcheltree, L.W., Stemler, F.W. (1997). The mouse ear model of cutaneous sulfur mustard injury. Toxicol. Methods 7 381-97. 

Dachir, S., Fishheine, E., Meshulam, Y., Sahar, R., Amir, A., Kadar, T. (2002). Potential anti-inflammatory treatments against cutaneous sulfur mustard injury using the mouse ear vesicant model. Hum. Exp. Toxicol. 21 197-203. 

Debouzy, J.C., Aous, S., Dabouis, V., Neveux, Y., Gentilbomme, E. (2002). Phospholipid matrix as a target for sulfur mustard (HD) NMR study in model membrane systems. Cell Biol. Toxicol. 18 397-408. 

Gerecke, D.R., Bhatt, P. et al. (2004). Sulfur mustard alters laminin 5 and gelatinase MNRA levels and increases gelati-nase activity in a mouse ear vesicant model. Proceedings of the 43rd Annual Meeting of the Society of Toxicology, Baltimore, MD, 1888 pp. 

Hinshaw, D.B., Lodhi, I.J., Hurley, L.L., Atkins, K.B., Dabrowska, M.I. (1999). Activation of poly [ADP-ribose] polymerase in endothelial cells and keratinocytes role in an in vitro model of sulfur mustard-mediated vesication. Toxicol. Appl. Pharmacol. 156 17-29. 

Kiser, R.C., Moore, D.M. et al. (2005). Mouse ear vesicant model (MEVM) evaluation of treatment combinations against topical sulfur mustard challenge. Toxicol. Set. 84 451. 

Reid, F.M., Niemuth, N.A., Shumaker, S.M., Waugh, J.A., Graham, J.S. (2007). Biomechanical monitoring of cutaneous sulfur mustard-induced lesions in the weanling pig model for depth of injury. Skin Res. Technol. 13(2) 217-25. 

Reid, F.M., Kiser, R.C., Hart, W.E., McGuirmess, E.E., Mann, J., Graham, J.S. (2008b). A sulfur mustard and thermal superficial dermal injury pig model. Proceedings of the U.S. Army Medical Defense Bioscience Review, 169 pp. 

Smith, K.J., Casillas, R., Graham, J., Skelton, H.G., Stemler, F., Hackley, B.E., Jr. (1997a). Histopathologic features seen with different animal models following cutaneous sulfur mustard exposure. J. Dermatol. Sci. 14 126-35. 

FIGURE 50.5. Concentration over time, following i.v. and respiratory exposure to sulfur mustard in the guinea pig model. A Decline of sulfur mustard exposure after intravenous injection. B Concentration over time after respiratory exposure initial increase in the inhalation phase, followed hy a decline and a secondary increase, concentration of approximately 2 ng/ml is sustained for 4h. 

Casillas, R.P., Kiser, R.C., Truxall, J.A., Singer, A.W., Shumaker, S.M., Niemuth N.A., Ricketts, K.M., Mitcheltree, L.W., Castrejon, L.R., Blank, J.A. (2000). Therapeutic approaches to dermatotoxicity by sulfur mustard. I. Modulaton of sulfur mustard-induced cutaneous injury in the mouse ear vesicant model. J. Appl. Toxicol. 20 S145-51. 

Ishida, H., Ray, R., Ray, P. (2008). Sulfur mustard dowmegulates iNOS expression to inhibit wound healing in a human kerati-nocyte model. J. Dermatol. Sci. 49 207-16. 

Margulis, A., Chaouat, M., Ben-Bassat, H., Eldad, A., Icekson, M., Breiterman, S., Neuman, R. (2007). Comparison of topical iodine and silver sulfadiazine as therapies against sulfur mustard bums in a pig model. Wound Repair Regen. 15 916-21. 

The product was also compared to Fuller s earth in a pig model. The potency of the RSDL/sponge was statistically better than Fuller s earth against skin injury induced by sulfur mustard, observed 3 days post-exposure. RSDL was more efficient than Fuller s earth in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. The potencies of the RSDL/sponge and Fuller s earth were similar to severe inhibition of plasma cholinesterases induced by VX poisoning. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin (Taysse et al, 2007). 

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