Biophysical Factors in Drug Action 23 



has increased by 10%, the rate of swelling slows down and stops, 

 but increases again rapidly when the insect is returned to the 

 mixture (figure lb). These effects can be repeated in smaller 

 increments, and are not dependent on vital transfer processes, 

 for they can be reproduced with the isolated cuticle attached 

 to a small osmometer filled with water. 



The penetration of the alcohol through the cuticle is clearly 

 dependent on the presence of kerosene in the cuticle framework. 

 This must be a very labile association, as the kerosene is readily 

 eluted from the cuticle when the insect is transferred from the 

 mixture into the pure alcohol. The penetration of alcohol which 

 is induced by kerosene is accompanied by a simultaneous increase 

 in the exosmosis of water from the cuticle. This can be observed 

 in the cloudy swirling zone near the surface of the cuticle indi- 

 cating that kerosene is thrown out of solution in this region. 

 The insect is not dehydrated when immersed in pure alcohol. 



Similar results can be obtained with methyl or propyl alcohol, 

 and with fat solvents such as ether, benzene, or chloroform 

 instead of kerosene. The synergistic action is also shown in 

 mixtures which contain structurally related components, such 

 as ethyl and octyl alcohol. Here, apart from its own toxicity, 

 the octyl alcohol increases the permeability of the cuticle to ethyl 

 alcohol, resulting in a progressive swelling of the insect which 

 does not occur in octyl alcohol alone. 



The problem which arises is to decide how fat solvents, which 

 are only slightly soluble in water, increase the permeability of 

 the cuticle to water-soluble fat solvents and also to water. Ex- 

 periments with isolated layers of the cuticles attached to os- 

 mometers show that the site of the increase in cuticle perme- 

 ability is in the outer lipophylic epicuticle. The inner thicker 

 endocuticle layer is very permeable to water, and exosmosis 

 of water takes place very rapidly when this layer is in contact 

 with ethyl alcohol or with alcohol-kerosene mixtures. We are 

 led to consider the possibility that the uptake of kerosene by 

 the epicuticle lipids does not involve only a simple swelling or 

 disorientation of this phase in situ, but also a displacement of 

 lipid from the more hydrated protein or lipo-protein components. 



