BIBLIOGRAPHY 485 



bimodal dose-response curve does not prevail in the bisdithiocarbamates 

 (174, 246). Bisdithiocarbamates are unstable (234), and several break- 

 down products have been suggested as the active toxicant. Disodium 

 ethylenebis[dithiocarbamate] itself is completely without fungicidal 

 action (247, 432). Carbon disulfide, one of the breakdown products, is 

 unlikely to be of primary importance (432). It appears that three de- 

 rived compounds, which arise by breakdown of the parent substance, all 

 contribute to toxicity: ethylene diwothiocyanate, ethylene thiuram 

 monosulfkle, and polymers of the thiuram monosulfide (197, 236, 237, 

 414). Reactivity with thiol groups has suggested that the primary toxic 

 action is on a sulfhydryl enzyme (197). 



1 1 . CONCLUDING REMARKS 



In his treatise on the principles of fungicidal action, Horsfall (174) 

 emphasizes the two requirements of a toxicant, that it be able in some 

 way to react with an essential cell constituent, and that it be able to 

 reach the site of this reaction. It seems fair to say that for no fungicidal 

 or fungistatic material can both these requirements be specified in terms 

 of structure. Nor does it seem likely to me that further empirical test- 

 ing of ever-different organic compounds will by itself allow us to draw 

 up accurate specifications as guides to both theory and practice. In- 

 stead, we need to know more about the toxicants we have, especially in 

 terms of the theory of chemical reactions. On the biological side of the 

 problem, a frontal attack on the problems of the cell surface is surely 

 an urgent necessity. It must be realized that, at the present time, all 

 explanations based on an assumed permeability or impermeability are 

 no more than guesses, in the absence of independent evidence; i.e., 

 evidence not based upon the toxic reaction itself. 



Although no line of investigation can, of course, be ruled out, it does 

 seem that the search in the fungi for specific enzymatic loci of toxicity 

 is less promising. Many of the most active materials may be general 

 rather than specific poisons; if this is true, they will inhibit almost any 

 enzyme the investigator happens to test, but none of these will be "the" 

 site of activity. 



BIBLIOGRAPHY 



1. Abelson, P. H. and E. Aldous. 1950. /. Bacteriol. GO: 401-413. 



2. Agerberg, L. S., R. Schick, M. Schmidt, and R. von Sengbusch. 1933. Zuchter 

 5: 272-280. 



3. Akai, S. and S. Itoi. 1954. Botan. Mag- (Tokyo) 67: 1-5. 



