HEAVY METALS 467 



if the ratio of complexing agent to metal is high — five to ten — toxicity 

 disappears (28). This is consistent with the concept that cell and com- 

 plex compete for copper; it is significant that ethylenediaminetetraace- 

 tate (EDTA), which forms very stable metal complexes, abolishes tox- 

 icity at a 1:1 molar ratio to copper (28, 302). Unfortunately, these 

 same observations are consistent also with a second explanation, that 

 the malate and glycine complexes enter the cell whereas the EDTA 

 complex does not. 



Organic mercurials are generally more toxic than inorganic, both to 

 bacteria (39) and to fungi (174, 372). Part of the answer to their 

 practical effectiveness lies in the appreciable volatility of some of them 

 (17, 88, 220). There is some evidence, however, that the effective or- 

 ganic mercurials penetrate the cell as such, i.e., that they are more 

 readily taken up than mercuric ions (35, 324). Against this may be 

 cited limited evidence from pH studies in a complete growth medium 

 (187) that phenylmercuric acetate is more toxic as the ion. In general, 

 both inorganic and organic mercurials affect the same enzymes and are 

 equally antagonized by thiols, although occasional secondary effects 

 complicate the picture, as in the case of pancreatic amylase (319). 



The extreme case of increase in toxicity by provision of a metal in an 

 organic molecule is found in a study of the fungitoxicity of tin com- 

 pounds (199). Stannous and stannic chlorides are essentially non-toxic, 

 but tri-n-butyltin acetate prevents the growth of fungi at 0.1-0.5 ppm. 



McCallan and Wellman (267) find that copper, silver, and mercury 

 are both fungistatic and fungicidal. Fungicidal action is, of course, a 

 function of time of exposure and of the method by which the spores 

 are washed free of toxicant. 



The action of heavy metals on fungi may be conveniently divided 

 into two topics: the uptake of metals by spores and the metabolic or 

 other effects of the metal once it has reached a sensitive site. 



We have already mentioned that metals, in common with other fungi- 

 static materials, are accumulated by fungus spores in very high concen- 

 tration and very rapidly (288, 290, 291). Some further light is cast on 

 this by earlier and technically less satisfactory studies on the effect of 

 copper and mercury on Tilletia tritici (34, 35, 36). Copper uptake was 

 found to follow the Freundlich adsorption isotherm, i.e., to be non- 

 linearly related to external copper concentration. Copper supplied as 

 an ionizable salt is removable by acid, but the copper of cupric ammo- 

 nium sulfate, a coordination complex, is not so removed. Finally, 

 ionic copper disappearing from solution is almost quantitatively ac- 

 counted for by other cations — H+, Fe++, Mg++, etc. — liberated from 

 the spore. 



