Carcinogenicity of the Herbicide Maleic Hydrazide

Abstract

MALEIC hydrazide, l,2-dihydropyridazine-3,6-dione, was synthesized in 1947 (ref. 1) and has since become an important herbicide with uses including inhibition of sprouting in vegetables and stored root crops, prevention of sucker production in tobacco plants and growth control of grass, and foliage², Maleic hydrazide is claimed to be selectively toxic to plants but not to bacteria, fungi, rodents or dogs³; it is, however, mutagenic to Drosophila melanogaster⁴ and Bacillus megatherium⁵, it reduces the fertility of pea aphids⁶, and produces cytotoxicity, mitotic inhibition and unbalanced growth in cultured mammalian cells⁷. The finding that maleic hydrazide induced breakage of heterochromatin besides mitotio inhibition in Vicia faba⁸ prompted this warning: “Since nearly all chromosome-breaking agents have so far proved to be cancer-producing as well, we must hope that the agricultural use of this new agent will not be encouraged before suitable tests are made.” Later tests claimed to show that maleic hydrazide is non-carcinogenic⁹. This conclusion seems at variance with the data on which it was based; for example, after weekly injections of 5 mg of maleic hydrazide as the diethanolamine salt during 14 months, an “unusually high” incidence of local sarcomas, in three out of fifty-two rats at risk with none in controls, was noted⁹. In other experiments, a total of 260 mg of maleic hydrazide7 in arachis oil was injected subcutaneously during 65 weeks, and three local sarcomas, one with a hepatoma, developed in three of six rats; it was concluded that the herbicide was clearly carcinogenic¹⁰.