Sulfur mustard animal 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. 

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. 

Central nervous system and cardiac anomalies have only been seen after extremely high doses of sulfur mustard and usually only in laboratory settings with animal models. Mustard gas casualties from the Iran-Iraq War (1979-1980) treated in Europe did not display severe central nervous system or cardiac abnormalities (Willems, 1989). On the other hand, persistent damage to the afferent nerve system was a common finding in patients suffering cutaneous mustard injuries (Thomsen, Eriksen, Smit-Nielsen, 1998). 

The toxicokinetics of sulfur mustard have been studied in various animal models, e.g., the rat, hairless guinea pig, small pig and marmoset monkey. 

The rat is a generally accepted model for toxicokinetic studies. Maisonneuve et al (1993) do not provide a rationale for choosing this rodent as an animal model for sulfur mustard intoxication. The authors only studied the intravenous (iv) toxicokinetics. 

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