title: Toxicity and metabolism of malachite green and leucomalachite green during short-term feeding to Fischer 344 rats and B6C3F1 mice.
abstract: Malachite green, an N-methylated diaminotriphenylmethane dye, has been widely used as an antifungal agent in commercial fish hatcheries. Malachite green is reduced to and persists as leucomalachite green in the tissues of fish. Female and male B6C3F1 mice and Fischer 344 rats were fed up to 1200 ppm malachite green or 1160 ppm leucomalachite green for 28 days to determine the toxicity and metabolism of the dyes. Apoptosis in the transitional epithelium of the urinary bladder occurred in all mice fed the highest dose of leucomalachite green. This was not observed with malachite green. Hepatocyte vacuolization was present in rats administered malachite green or leucomalachite green. Rats given leucomalachite green also had apoptotic thyroid follicular epithelial cells. Decreased T4 and increased TSH levels were observed in male rats given leucomalachite green. A comparison of adverse effects suggests that exposure of rats or mice to leucomalachite green causes a greater number of and more severe changes than exposure to malachite green. N-Demethylated and N-oxidized malachite green and leucomalachite green metabolites, including primary arylamines, were detected by high performance liquid chromatography/mass spectrometry in the livers of treated rats. 32P-Postlabeling analyses indicated a single adduct or co-eluting adducts in the liver DNA. These data suggest that malachite green and leucomalachite green 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.
authors.affiliation: National Center for Toxicological Research, Jefferson, AR 72079, USA. sculp@nctr.fda.gov
authors.forename: S J
authors.initials: SJ
authors.lastname: Culp
authors.forename: L R
authors.initials: LR
authors.lastname: Blankenship
authors.forename: D F
authors.initials: DF
authors.lastname: Kusewitt
authors.forename: D R
authors.initials: DR
authors.lastname: Doerge
authors.forename: L T
authors.initials: LT
authors.lastname: Mulligan
authors.forename: F A
authors.initials: FA
authors.lastname: Beland
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005659:Fungicides, Industrial / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012394:Rosaniline Dyes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013045:Species Specificity; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013972:Thyrotropin / Q000097:blood; D018675:Toxicity Tests; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
chemical_list: D000814:Aniline Compounds; D018736:DNA Adducts; D005659:Fungicides, Industrial; D012394:Rosaniline Dyes; C005095:malachite green; C015320:leucomalachite green; D013972:Thyrotropin