128 FUNGUS DISEASES OF MAN AND ANIMALS 



results were due to their using rabbits which had somehow become 

 sensitized to the proteins of this mold. Henrici obtained a toxin 

 from R. nigricans which, when injected into rabbits, killed some, 

 but caused anaphylactic reactions only in surviving rabbits given 

 a second injection. 



A number of investigators have been concerned with the toxins of 

 A. fumigatus because of the high and constant virulence of this 

 fungus for laboratory animals. Renon *^ was unable to find any 

 toxic substance either in the medium or by extracting the mycelium 

 with various solvents. Similar results were obtained by Kotliar,^- 

 Mace,^* and by Martins,^^ although the latter author did observe 

 death with one rabbit inoculated with spores heated to 100° C. 



On the other hand, Ceni and Besta ^^ found in extracts of A. 

 jumigatus a heat-stable toxic substance affecting mainly the nervous 

 system, and this was confirmed by Bodin and Gautier.'^ Bodin and 

 Lenormand ^ studied the matter further and concluded that there 

 were two toxins, one a substance soluble in fat solvents which pro- 

 duced convulsions and a rapid death in rabbits, the other a volatile 

 substance obtained by distillation which produced paralysis and 

 death in guinea pigs. 



Henrici ^^ obtained a toxin from the cell sap of a strain of A. 

 jumigatus isolated from aspergillosis in a chick. The toxin was 

 extracted from a glucose-peptone broth culture by squeezing from 

 the mycelial mat as much of the medium as possible, mincing the 

 mycelium with scissors, passing it repeatedly through a food chopper, 

 and expressing the cell sap in a hydraulic press. The toxin resembled 

 the so-called toxalbumins, the exotoxins of bacteria, and the snake 

 venoms in sensitivity to heat, hemolytic action, production of local 

 necrosis and edema, delayed action, and antigenicity. Unlike the 

 toxalbumins, however, its toxicity was augmented rather than de- 

 stroyed by sodium ricinoleate and it appears to be non-protein in 

 nature. In these characteristics and in the type of lesions it produces 

 in animals it resembles the toxin of the poisonous mushroom Amanita 

 phalloides. 



The cell sap was lethal by subcutaneous, intraabdominal, and 

 intravenous injection (but not by mouth) for rabbits, guinea pigs, 

 mice, and chicks. Injected subcutaneously in rabbits it produced 

 in about 5 hours large boggy lesions in which there was a large 

 amount of gelatinous fluid similar to that in lesions caused by the 

 toxin of Clostridium oedematiens. After a few days the swelling 

 subsided, the center became necrotic and sloughed away leaving an 

 ulcer which required about 10 days to heal. Guinea pigs reacted 



