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MG undergoes a reduction to LG. LG could also undergoes a similar N-demethylation by cytochrome P-450. These primary and secondary amine metabolites are similar to carcinogenic arylamines.

Dermal absorption of MG is negligible.

Key value for chemical safety assessment

Additional information

Malachite Green (MG) undergoes a reduction to Leucomalachite Green (LG).

MG undergoes a reduction to LG or cytochrome P-45O catalyzed N-demethylation to mono-and di-desmethyl MG. LG could also undergoes a similar N-demethylation by cytochrome P-450. These primary and secondary amine metabolites are similar to carcinogenic arylamines. As such, they could be oxidized to metabolites that react with DNA either directly or after esterilication. Misreplication of these lesions may result in mutations that can lead to liver tumors (Culp, 1999). A comparison of adverse effects suggests that exposure to LG causes a greater number and more severe changes than exposure to MG (Culp, 1999).

Furthermore the complete reduction of MG to LG can occur by the action of intestinal bacteria: intestinal microflora from human, rat, mouse and monkey and anaerobic bacteria (representative of those found in the human gastrointestinal tract) metabolize MG to LG. Since LG is structurally similar to the Leuco-forms of other carcinogenic triphenylmethane dyes, it is expected that the enzymatic reduction of MG to LG by intestinal microflora may play a role in metabolic activation of the substance to a potential carcinogen (Henderson, 1997).

Dermal absorption of both MG Oxalate and Chloride is negligible and the formation of LG is also negligible (R&C, 2011).

A comparison of adverse effects suggests that exposure to LG causes a greater number and more severe changes than exposure to MG. LG produces apoptosis of the transitional epithelium of the urinary bladder, in mice. The apoptotic cells are phagocytized by neighboring transitional epithelial cells and appear to undergo dissolution in phagocytic vacuoles. The apoptotic cell death may be accompanied by a compensatory cell proliferation, which can promote the expansion of initiated cells.

The formation of a DNA adduct or co-eluting adducts (that increases with increasing dose) occurred in rats and mice fed with MG and LG; this suggests that a genotoxic mechanism for thyroid tumour formation may be possible (Culp, 1999).

In addition results suggest a scenario in which MG undergoes to the LG reduced form, or cytochrome P-45O catalyzed N-demethylation to mono-and di-desmethyl MG. LG may also undergo a similar N-demethylation by cytochrome P-450. These primary and secondary amine metabolites are similar to carcinogenic arylamines. As such, they could be oxidized to metabolites that react with DNA either directly or after esterilication. Misreplication of these lesions may result in mutations that can lead to liver tumour (Culp, 1999).