Sulfur mustard dermal absorption

ORNL also considered calculating an SF on the basis of the U.S. Environmental Protection Agency s (EPA 1991) estimated inhalation unit risk (8.5 x 10 per pg/m ) of sulfur mustard. Normalizing the inhalation unit risk for a 70-kg person inhaling 20 m of air per day would yield an SF of 0.3 per pg/kg per day. ORNL decided not to use this method because the inhalation study (McNamara et al. 1975) used to estimate the inhalation unit risk resulted in rat skin tumors that appeared to be caused by dermal exposure rather than by systemic absorption and distribution to the skin, and inhalation-to-oral extrapolation was not considered appropriate. Furthermore, the McNamara et al. (1975) study contained a number of deficiencies, such as outdated testing protocols, brief exposures, and small numbers of animals, which made quantitative analysis difficult. 

With its high lipophilicity, toxicologically relevant amounts of sulfur mustard are absorbed into epithelial tissue (Papirmeister et al, 1991). Dermal absorption is dependent on the thickness of the epidermis and on the presence of moisture, which enhances penetration. Absorption tends to be greater at the base of hair shafts and in the hair follicle where the epithelial tissue is thinner than the surrounding surface area (Papirmeister et al, 1991). Approximately 20% of sulfur mustard applied to skin may be rapidly... 

For dermal exposure, penetration rates over 2-8 h ranged from 2.9 to 6.7% and rates of absorption from 1.2 to 4.0% following application of400 pg of radiolabeled sulfur mustard per cm of isolated perfused porcine skin (Riviere et a/., 1995). The average total recovery of the radiolabel was 9.3% (3.8-17.7%) suggesting substantial loss due to volatdization. 

Relative to dermal absorption, little is known about absorption in the respiratory tract. Cameron et al (1946) calculated the absorption of sulfur mustard vapor in the noses of rabbits and rhesus monkeys. The concentration of the agent in the nasal passages was 10-30% of the chamber concentrations (40, 100, and 500mg/m ), implying an absorption of approximately 70-90%. 

Little information is available regarding the toxieokineties of lewisite. Lewisite is readily absorbed by mueous membranes and, beeause of its lipophilicity, dermal absorption is signitieant (HSDB, 2004). Dermal absorption is reportedly more rapid than for sulfur mustard (Hurst and Smith, 2008). Axehod and Hamilton (1947) reported that radiolabeled ( " As) lewisite applied to a 0.4S em area of human skin was primarily fixed on the epidermis and that very little was found in the dermis most was detected in hair and hair follicles. In experiments with guinea pigs, histological examination revealed that lewisite applied to skin entered epidermis within 2 min and penetrated into the dermis within 10 min (Ferguson and Silver, 1947). Only trace amounts were detectable in the dermis at 24 h post-application. 

Sulfur mustard is a blistering or vesicating agent that primarily incurs damage at the organs that come into immediate contact with either its liquid or vaporous form. However, severe dermal and respiratory exposure to the agent may also result in the absorption of sulfur mustard that subsequently causes additional systemic damage (Kehe and Szinicz, 2005). 

It was, however, surprising that the skin-blistering agent sulfur mustard decreased dermal absorption and penetration of permethrin (Riviere et al., 2002). It is safe to assume that this interaction is based on the disposition of sulfur mustard in skin and... 

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