MALEIC HYDRAZIDE 335 



actions of adenine on root tip cells, and concluded that maleic hydrazide 

 might be a pyrimidine or purine antagonist. Callaghan and Grun (1961) 

 noted that maleic hydrazide-C^^ becomes fixed in the nuclei of root tip cells 

 and remains there for long periods, and postulated that the incorporation 

 may follow the pathway of RNA synthesis, due to the structural similarity 

 to uracil, the end product being a modified RNA. It would be quite easy 

 to determine if this is the case, but as far as I know it has not been done. 



Effects on Animals 



It is noteworthy, as Crafts (1961 a) has pointed out, that maleic hydrazide 

 is selectively toxic to plants and does not inhibit growth in bacteria, fungi, 

 algae, or animals. The conclusion is that maleic hydrazide affects some 

 process unique to plants. It was also a point of some concern during the 

 early use of maleic hydrazide as a herbicide that it might be carcinogenic, 

 since Darlington and McLeish (1951) remarked that the chromosomal 

 effects observed in plants could, if they occurred in animal cells, lead to 

 tumors. A thorough investigation was made by Barnes et al. (1957), who 

 found that remarkably high doses are tolerated by mammals. The LD50 

 for rats is 4 g/kg and they are unaffected by a diet containing 1% maleic 

 hydrazide throughout their lifetime. Rats were injected subcutaneously 

 with 500 mg/kg/week for 14 months; of the 52 animals treated, 3 developed 

 sarcomata, and there was none in the controls. Further work was done 

 and both rats and mice were fed a diet 1% in maleic hydrazide for 100 

 weeks; there was no effect on the growth or health of the animals, and the 

 incidence of tumors was the same in the treated and control groups. Maleic 

 hydrazide applied to mouse skin showed no carcinogenic activity, nor 

 does 1 mM maleic hydrazide affect mitoses in rat ear epidermis, and even 

 10 mM does not depress the growth of explants from guinea pig ears. 

 No carcinostatic effect in rats bearing Walker tumors was observed. The 

 lack of action in animals cannot be ascribed to a rapid metabolism of maleic 

 hydrazide, since it was shown that 43-62% of the substance administered 

 to rabbits is excreted unchanged within 48 hr. The fate of the remainder 

 is unknown. Mannel and Grice (1957 a, b) fed rats a diet containing 2% 

 maleic hydrazide for 6 months and found no effect on the liver with respect 

 to weight, size, number of cells, histology, RNA or DNA content, or phos- 

 pholipid content, and concluded that maleic hydrazide is not carcinogenic 

 for the liver. The relative lack of effect on organisms other than plants 

 thus seems to be well established, but at present the reason for this se- 

 lectivity is not understood. 



