Toxicity and metabolism of malachite green and leucomalachite green duringshort-term feeding to Fischer 344 rats and B6C3F(1) mice

Malachite green, an N-methylated diaminotriphenylmethane dye, has been wide ly used as an antifungal agent in commercial fish hatcheries. Malachite gre en is reduced to and persists as leucomalachite green in the tissues of fis h. Female and male B6C3F(1) mice and Fischer 344 rats were fed up to 1200 p pm malachite green or 1160 ppm leucomalachite green for 28 days to determin e the toxicity and metabolism of the dyes. Apoptosis in the transitional ep ithelium of the urinary bladder occurred in all mice fed the highest dose o f leucomalachite green. This was not observed with malachite green. Hepatoc yte vacuolization was present in rats administered malachite green or leuco malachite green. Rats given leucomalachite green also had apoptotic thyroid follicular epithelial cells. Decreased T4 and increased TSH levels were ob served in male rats given leucomalachite green. A comparison of adverse eff ects suggests that exposure of rats or mice to leucomalachite green causes a greater number of and more severe changes than exposure to malachite gree n. N-demethylated and N-oxidized malachite green and leucomalachite green m etabolites, including primary arylamines, were detected by high performance liquid chromatography/mass spectrometry in the livers of treated rats. P-3 2-PostlabeIing analyses indicated a single adduct or co-eluting adducts in the liver DNA. These data suggest that malachite green and leucomalachite g reen are metabolized to primary and secondary arylamines in the tissues of rodents and that these derivatives, following subsequent activation, may be responsible for the adverse effects associated with exposure to malachite green. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reser ved.