The fate of arsenical vesicants in the skin and the effect of BAL (British anti-lewisite)

Abstract

The work described in this paper was carried out on behalf of the Ministry of Supply, and preliminary accounts of it were circulated by the Ministry in 1943 and early in 1944. A quantitative investigation was made of various factors concerned in the disappearance of arsenic from the skin after the application of an arsenical vesicant. These factors determine the severity of the local and systemic effects caused by a given amount of a vesicant. Phenyldichloroarsine and lewisite I (,-chlorovinyldichloroarsine) were studied, using rabbits as experimental animals. The amount of arsenic removed from the skin by absorption into the general circulation or evaporation of the vesicant, and the fraction of the residual arsenic which was fixed by combination with skin constituents, were determined at varying periods after applying the vesicant. The effect of varying the amount of vesicant applied to a given area of skin was examined. Stocken & Thompson (1946) had previously found that BAL (British Anti-Lewisite, 2:3-dimercaptopropanol) diminished the amount of arsenic remaining in the skin of rats 48 hr. after contamination with lewisite. Experiments were done to discover the way in which BAL modifies the fate of arsenical vesicants in the skin.EXPERIMENTAL General method8 The vesicants (obtained from the Ministry of Supply) were purified by distillation in vacuo. They were applied to the skin as freely falling drops, measured from the 'burette' devised by Lane (1946) or from the modification of this instrument developed by Levvy (1946). The amounts of liquid to be measured were so very small that they could be delivered accurately only in the form of discrete drops. In using Lane's instrument, it was found convenient to retard the drop rate by applying a negative hydrostatic pressure to the column of vesicant. In experiments with phenyldichloroarsine, two different drop sizes were employed (5 and 0-5 mg.), and in the case of lewisite I, three (4.5, 0 5 and 0-133 mg.). The exact weight of the drop applied in an individual experiment was calculated from the readings given by the instrument at the time, and this figure was used in working out the results. For drops of any one magnitude, the range from experiment to experiment in the calculated figure for the weight was not more than 5% of the mean.The rabbits used ranged in weight from 2 to 3 kg. and were of both sexes. For treatment with the vesicant, an area of skin on the back was freed from fur by clipping closely with scissors. One or more circles, approximately 3 cm. in diameter, were drawn in Indian ink on the skin, as far apart as possible if there were more than one. One drop of vesicant was allowed to fall on to each of these marked out 'spots'. In some cases the spot was immediately covered with a glass vessel, 2 cm. in diam. and 1 cm. in depth, which was firmly attached to the skin with adhesive plaster. Open glass cylinders of the same dimensions were secured to spots which were to be left uncovered so as to prevent the animal from removing the vesicant. The an...