Sulfur mustard toxicokinetics

A. Maisonneuve, I. Callebat, L. Debordes and L. Coppet, Biological fate of sulfur mustard in rat toxicokinetics and disposition, Xenobiotica, 23, 771-180 (1993). 

An enzyme-linked immunosorbent assay (ELISA) was developed by Van der Schans and colleagues for detection of the mustard adduct within DNA, using monoclonal antibodies raised against N7-HETE-guanosine-5 -phosphate coupled to keyhole limpet hemocyanin (n). The ELISA was successfully applied in toxicokinetic studies in which levels of adducted DNA were followed in conjunction with measurement of intact sulfur mustard (12). 

Riviere, J.E., Brooks, J.D., Williams, P.L., Monteiro-Riviere, N.A. (1995). Toxicokinetics of topical sulfur mustard penetration, disposition, and vascrdar toxicity in isolated perfused porcine skin. Toxicol. Appl. Pharmacol. 135 25-34. 

Zhang B, Wu Y. Toxicokinetics of sulfur mustard. Chinese J Pharm Toxicol. 1987 1 188-194. 

Vesicants, including sulfur mustard and lewisite, are the subject of the second main part of this chapter. Coherences of invasion and distribution are presented, and the major processes of biotransformation and elimination caused by binding to proteins [and more prominently, to deoxyribonucleic acid (DNA)] are discussed. Finally, we make some comments about current bioanalytical approaches. This chapter provides readers with a comprehensive overview of tire toxicokinetics of OP nerve agents and vesicants. 

Langenberg, J.P, Van der Schans, G.P., Spruit, H.E., et al, 1998b. Toxicokinetics of sulfur mustard and its DNA-adducts in the hairless guinea pig. Drug Chem. Toxicol. 21,131-147. 

In order to study the toxicokinetics of sulfur mustard, a method to determine the compound in biological matrices (blood and tissues) is needed, preferably with a sensitivity that allows quantitative analysis below the level of toxicological relevance. In several studies, " C-labeled sulfur mustard has been used, which allows for convenient and sensitive analysis, but since only radioactivity is measured, the identity of the measured compound(s) is not confirmed, which may be considered a drawback of this approach. 

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. 

Zhang and Wu (1987) chose the small pig (male and female, black, 4.2-13.0 kg) because of the aforementioned resemblance of its skin to that of humans. They chose this model to study the percutaneous toxicokinetics of occluded liquid sulfur mustard, and studied the iv route in this species as the reference route, as well as the toxicokinetics after subcutaneous (sc) exposure. 

The respiratory route is also highly relevant for sulfur mustard. Due to their complex nasal system, rats and guinea pigs may not be the best models for humans when studying the inhalation toxicokinetics of sulfur mustard vapor. In this respect, the marmoset monkey, a small non-human primate, is a better choice. The group of Langenberg et al. studied the inhalation toxicokinetics of sulfur mustard in this species (male and female, ca. 300-500 g), using the iv route as a reference. ... 

Figure 7.1 Concentration-time profiles for iv bolus administration of sulfur mustard to the rat (solid line, 10 mg kg ), HGP (0.3 U) 2Af> mg kg and 1 LD50/8.2 mg kg ), pig (10 mg kg ) and marmoset (8.2 mg kg" ). The toxicokinetic parameters used to draw these curves are presented in Table 7.1. HGP hairless guinea pig.

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