Systematic Studies on the Toxicity of Nitrofuran Derivatives (I)

Abstract

The toxic effects of nitrofurazone have been investigated in rat testis histopathologically.Marked atrophy of the testis, severe degeneration and necrosis of the seminiferous epithelium were selectively caused by continued high oral administration of nitrofurazone. The testis weight of treated animals was reduced to half of its of controls by 10 days feeding of 0.1% dietary level. Histologically, it was observed that mature spermatozoa, spermatid, and secondary spermatocyte were primarily affected, and primary spermatocyte and spermatogonia were delayed in the destruction, but no changes were noted in the Sertoli cells, interstitial cells, and basement membrane of the tubules by the one month's treatment. Three months after the first administration, however, moderate hyperplasia of Leydig cells and slight thickening of the basement membrane were recognized.Testicular degenerative changes were arised from 3 days feeding of 0.1% dietary level, and minimal toxic dose to the testicular epithelium was at the 0.06% level of nitrofurazone in the diet.Almost complete anatomical restoration of the seminiferous epithelium recognized in 60 days after return to the basal diet followed 32 days' administration of the drug. It was shown that regenerative activity was considerably well preserved even in the long duration of the treatment.It was proved that maximal dose of the nothing of the testicular changes in the rat was about 35mg/kg of nitrofurazone a day, and this dose was corresponding to 2, 500 pieces of fish sausage (net weight 140g) in a man of the body weight of 50kg. From these results, it may be considered that the use of nitrofurazone as a food preservative is practically non-toxic.