Abstract for TER82080

Teratologic Evaluation of Gentian Violet in New Zealand White Rabbits

CASRN: 548-62-9
Chemical Formula: C25H30ClN3
Molecular Weight: 407.986
Report Date: March 15, 1983


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Gentian Violet, a commonly used topical antimicrobial agent, was evaluated for teratogenicity following maternal exposure. Artificially inseminated New Zealand white rabbits were dosed by gavage on gestational days 6 through 19 with gentian violet (0, 0, 0.5, 1.0 or 2.0 mg/kg/day) with distilled water as vehicle. These dose groups are referred to as GV-0.0, GV-0.5, GV-1.0 and GV-2.0 respectively. Does were weighed on gestational days 0, 6-19 (prior to daily dosing) and 30 (immediately prior to sacrifice), and were also observed for clinical signs of toxicity. At sacrifice on gestational day 30, does were evaluated for body weight, liver weight, gravid uterine weight and status of uterine implantation sites (i.e., implantation sites, resorptions, dead fetuses, live fetuses). Live fetuses were dissected from the uterus and evaluated for live litter size, body weights, sex ratios and gross morphological abnormalities. All live fetuses were examined for visceral malformations employing the Staples' fresh tissue dissection method. Half of the fetuses were decapitated immediately after dissection and the heads were fixed in Bouin's solution for free hand sectioning and examination (Wilson's Technique). All fetal carcasses were cleared and stained with Alizarin Red S and examined for skeletal malformations.

The maternal mortality in the present study was 22.6% (7/31 does) in the GV-2.0 group, 15.4% (4/26) in the GV-1.0 group, 7.4% (2/27) in the GV-0.5 group and 0.0 (0/27) in the GV-0.0 group. A significant trend was seen toward reduction in maternal body weight on gestational day 19 (end of dosing), and in maternal weight gain (gestational period and treatment period). For maternal weight gain, all GV-exposed groups were significantly lower than for controls for both treatment and gestation period. Clinical signs, seen in a dose-related manner, included wheezing, diarrhea, congestion, wet nose, dyspnea, lacrimation, and anorexia and cyanosis (the latter two in those does which died).

All GV-exposed groups exhibited a significant increase in the number of implantation sites per litter versus controls. Percentage of resorptions per litter and number of litters with resorptions, as well as the percentage of non-live (dead plus resorbed) and affected (nonlive plus malformed) per litter exhibited a dose-related upward trend, but no significant pairwise comparisons. For live litters, the number of fetuses (male and/or female) per litter did not differ among dose groups. Average fetal body weight per litter exhibited a significant downward trend with all dose group values significantly lower than controls. When separated by sex, only female fetal body weight per litter exhibited a significant downward trend and pairwise comparisons. There were no significant dose-related effects on the incidence of gross, visceral or skeletal malformations per litter, nor in the number (or percent) of fetuses, males or females, malformed per litter nor in the number or percent of litters with malformed fetuses. Examination of malformation incidence by category indicated no malformations unique to or with a higher incidence in any of the GV-exposed groups relative to controls.

In conclusion, no evidence of teratogenicity of gentian violet was seen when administered by gavage to pregnant NZW rabbits during organogenesis at doses which produced evidence of maternal and fetal mortality and toxicity.