Methanaminium, N-[4-[[4-(dimethylamino)phenyl]phenylmethylene]-2,5-cyclohexadien-1-ylidene]-N-methyl-, ethanedioate

Endpoint summary

Description of key information

MGC rat LOEL (28d): 40 mg/kg bw/day (males and females)

MGC mouse LOEL (28d): 50 mg/kg bw/day (males)

MGC mouse LOEL (28d): 20 mg/kg bw/day (females)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

20 mg/kg bw/day

Study duration:

subacute

Species:

mouse

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The current 28-day studies (Culp et al., 2004) were conducted as part of an overall effort by the NTP to determine the toxicity and carcinogenicity of malachite green chloride. Male and female rats and mice were exposed to malachite green chloride (95 % pure) or leucomalachite green (99 % pure) (male rats and female mice only) in feed for 28 days. Animals were evaluated for clinical pathology and histopathology.

Groups of 8 male and 8 female rats and mice were fed diets containing 0, 25, 100, 300, 600, or 1200 ppm malachite green chloride for 28 days. Additional groups of 8 male and 8 female rats designated for thyroid hormone assays were fed diets containing 0 or 1200 ppm malachite green chloride. Groups of 8 male rats and 8 female mice were fed diets containing 0, 290, 580, or 1160 ppm leucomalachite green for 28 days. Additional groups of eight male rats designated for thyroid hormone assays were fed diets containing 0 or 1160 ppm leucomalachite green.

Exposure concentrations of 25, 100, 300, 600, and 1200 ppm resulted in average daily doses of 3 to 190 mg malachite green chloride/kg body weight to male and female rats and 5 to 250 mg/kg to male and female mice. In the leucomalachite green study, feed consumption by all groups of exposed male rats was similar to that by the controls. Dietary concentrations of 290, 580, and 1160 ppm resulted in average daily doses of approximately 30, 60, and 115 mg leucomalachite green/kg body weight to male rats and approximately 62, 110, and 220 mg/kg to female mice.

All rats and mice survived to the end of the studies. In the malachite green chloride study, the body weight gain of males rats in the 1200 ppm group was significantly less than that of the controls. The final mean body weight of female rats and mice in the 1200 ppm groups and the body weight gains of female rats and mice in the 600 (rats only) and 1200 ppm groups were significantly less than those of the controls. In the leucomalachite green study, the final mean body weight of male rats and female mice in the 1160 ppm groups and the mean body weight gains of male rats and female mice in the 580 and 1160 ppm groups were significantly less than those of the control groups.

In the malachite green chloride study, feed consumption by all exposed groups of male and female rats and mice was generally similar to that by the control groups. In female rats exposed to malachite green chloride, there was a significant increases in γ-glutamyltransferase activities with an activity in 1200 ppm females seven times greater than that in the controls. Likewise, γ-glutamyltransferase activity in male rats exposed to 1160 ppm leucomalachite green was twice that in the controls. On days 4 and 21, the concentration of thyroxine was significantly decreased in male rats exposed to 1160 ppm leucomalachite green and the concentration of thyroid-stimulating hormone was significantly increased.

In the malachite green chloride study, the relative liver weights of 600 and 1200 ppm male rats and the relative and absolute liver weights of 300 ppm or greater female rats were generally significantly greater than those of the controls. In the leucomalachite green study, the relative liver weights of 290 ppm or greater male rats were significantly greater than those of the control group.

No gross lesions were observed in rats or mice and no microscopic lesions were observed in female mice that were attributed to malachite green chloride exposure. Microscopically, the incidences of hepatocyte cytoplasmic vacuolization were significantly increased in 1200 ppm male and female rats exposed to malachite green chloride. No gross lesions were observed in rats or mice that could be attributed to leucomalachite green exposure. Microscopically, the incidences of hepatocyte cytoplasmic vacuolization were significantly increased in 580 and 1160 ppm male rats. The incidence of multifocal apoptosis in the transitory epithelium of the urinary bladder was significantly increased in 1160 ppm female mice exposed to leucomalachite green.

The Lowest Dose Producing a Significant Effect in male and female rats treated with malachite green was indicated to be 300 ppm (40 mg/kg bw/day); the Lowest Dose Producing a Significant Effect in female mice was 100 ppm (20 mg/kg bw/day), while in male mice was 300 ppm (50 mg/kg bw/day).