|Evaluation year: ||2008|
|Comments: ||MG is metabolically reduced by fish to leucomalachite green (LMG). When fish exposed to MG reach the consumer, the amount of LMG present in the fish is expected to be higher than that of MG. As LMG is the predominant residue found in fish tissues following exposure to MG, it is the residue of primary concern from a safety point of view. Also, following ingestion, MG is reduced to LMG before absorption. LMG induces hepatocellular adenomas and carcinomas in female mice via a mutagenic mode of action. Based on these considerations, the Committee considered it inappropriate to establish an ADI for MG and did not support the use of MG for food-producing animals. The Committee considered hepatocarcinogenicity in female mice treated with LMG to be pivotal in the risk assessment of MG and LMG and evaluated the sum of MG and LMG in food expressed as LMG. The Committee used the BMDL10 value of 20 mg LMG/kg bw/d derived from the carcinogenicity study in female mice as the reference point for the MOE calculation. Assuming a daily consumption of 300 g of fish contaminated with MG, comparison of these dietary exposures of 0.15 μg/kg bw/d to sum of MG & LMG (mean) & 0.69 μg/kg bw/d (97.5th percentile) with the BMDL10 of 20 mg/kg bw per day indicates MOEs of 130 000 and 30 000, respectively. In the case that MG had been used to treat fish in aquaculture and the fish had been subjected to various depletion times, comparison of these exposure levels of 9 μg/kg bw/d (median, no depletion time) & 1 μg/kg bw/d (median, depletion time of 500 h) with the BMDL10 of 20 mg/kg bw per day indicates MOEs of 2000 and 20 000, respectively. The 97.5th percentile intakes were about 23 (no depletion time) and 2 μg/kg bw/d (depletion time of 500 h), respectively, providing MOEs of about 900 and 10 000. The Committee agreed that MOEs of less than 10 000 for genotoxic and carcinogenic contaminants indicate a health concern.
|MRL Comment: ||The Committee did not recommend MRLs for malachite green and leucomalachite green, as it did not support the use of malachite green for food-producing animals.|
|Intake: ||0.15 μg/kg bw/d to sum of MG & LMG (mean) & 0.69 μg/kg bw/d (97.5th percentile) for consumers of 300 g of contaminated fish/day. If MG had been used to treat fish in aquaculture and the fish had been subjected to various depletion times (summed MG & LMG): 9 μg/kg bw/d (median, no depletion time) & 1 μg/kg bw/d (median, depletion time of 500 h); 97.5th percentile intakes: 23 (no depletion time) and 2 μg/kg bw/d (depletion time of 500 h).
|Tolerable Intake: ||NONE ESTABLISHED; genotoxic carcinogen|
|Report: ||TRS 954-JECFA 70|
|Tox Monograph: ||MALACHITE GREEN.pdf|
|Specification: ||FAO JECFA Monographs 6(2009)|
Best estimate: 0.15-0.69 (sum vet. Drug + contaminant) µg/kg bw/day
|Pivotal Study: ||Mouse carcinogencity study (Culp et al, 2006): Female mice (n= 47-48/group) fed diets corresponding to intakes of 0, 15, 31 and 63 mg LMG/kg bw/d for 104 weeks. The only finding: dose-related trend in increased incidence of hepatocellular adenomas or carcinomas, incidence being statistically significant in the highest dose group.|
|Animal specie: ||B6C3FF1/Nctr Br|
|Effect: ||Hepatocellular adenomas and carcinomas|
|NOAEL: ||Not determined|
|Point of departure: ||BMDL10: 20 mg/kg bw/day|