Biological fate of sulphur mustard (1,1′-thiobis(2-chloroethane)): uptake, distribution and retention of³⁵S in skin and in blood after cutaneous application of³⁵S-sulphur mustard in rat and comparison with human bloodin vitro

Abstract

1. During the 6-h occluded cutaneous application of 35S-sulphur mustard vapour to rat, most of the dose, approximately 75%, passed through the skin and was systemically-distributed. Up to 25% of the 35S was retained in the skin, up to 30% was excreted in the urine and 5-8% was present in the blood, by the end of the application. 2. 35S initially declined rapidly in skin and then more slowly with a half-life of approximately 7.4 days. Some of the early loss was as sulphur mustard vapour from a possible depot of this compound which was larger with increase in dose. There was some apparent continuing uptake from such a depot into the systemic circulation. 3. The decline of 35S in blood was much slower than that from skin. About one-fifth of the original post-exposure level in the blood still present 6 weeks later. 4. The 35S in blood was mainly in the red cell contents as reaction products of haemoglobin with sulphur mustard. Its persistence in the systemic circulation, after an initial rapid decline due to its removal from the plasma, reflected the 65 day life span of these cells. Significant levels of 35S were found in the plasma only for a few days (t1/2 = 2.4 days). 5. Uptake and subsequent distribution of 35S in rat and human blood in vitro during gradual exposure to 35S-sulphur mustard using a novel method were similar. 35S in the red cells was associated mainly with the haemoglobin protein, but slightly greater binding with human, rather than with rat, plasma components was indicated.

Accumulation of intact sulfur mustard in adipose tissue and toxicokinetics by chemical conversion and isotope-dilution liquid chromatography–tandem mass spectrometry

“…Whole blood samples were employed instead of plasma samples in our study since the preliminary experiments showed that intact SM in plasma only accounted for about 14.6 % of that in blood, which was consistent with the previous reports that SM and related compounds were mainly in the red blood cells (Hambrook et al 1993). Moreover, the separation of plasma is time-consuming.…”

“…It was reported that when applying liquid SM to skin, 80 % of SM evaporated and only 20 % penetrated the skin, of which no more than 20 % was remained in skin and the rest entered into the circulation (Renshaw 1946). However, after occluded percutaneous application of SM for 6 h, approximately 75 % of the applied SM was absorbed (Hambrook et al 1993), indicating that different exposure way or operation methods may lead to different results in toxicokinetic studies.…”

Protective effect of povidone iodine ointment against skin lesions induced by chemical and thermal stimuli

“…[2][3][4] Owing to its lypophilic properties, it rapidly penetrates the skin. 5,6 Topical application of HD may cause erythema, which appears within hours of exposure followed by oedema, blistering and ulceration. 7,8 There is an urgent need for an efficient pharmacological antidote against mustard gas toxicity.…”

Mustard gas crosslinking of proteins through preferential alkylation of cysteines

“…However, mustard reactivity with nucleotides alone appears insufficient to explain all of the effects of mustard exposure (Watson and Griffin, 1992;Vaughan et al, 1988). It has long been known that mustard is capable of modifying proteins (Watson and Griffin, 1992;Kirner, 1946;Hambrook et al, …”