Abstract for TER82079

Teratologic Evaluation of Gentian Violet in CD Rats

CASRN: 548-62-9
Chemical Formula: C25H30ClN3
Molecular Weight: 407.986
Report Date: May 31, 1982


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 Viole a commonly used topical antimicrobial agent, was evaluated for teratogenicity following maternal exposure. Timed-pregnant CD rats (minimum 20 per dose group) were dosed by gavage on gestational days 6 through 15 with gentian violet (0.0, 2.5, 5.0 or 10.0 mg/kg/day) with distilled water as vehicle. These dose groups are referred to as GV-0.0, GV-2.5, GV-5.0 and GV-10.0 respectively. Dams were weighed on gestational days 0, 6-15 (prior to daily dosing) and 20 (immediately following sacrifice), and were also observed for clinical signs of toxicity. At sacrifice on gestational day 20, dams 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 prior to 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 rate in the present study was 9.4% (3/32 dams) in the GV-10.0 group; all other dams from all dose groups survived to terminal sacrifice on gestational day 20. A significant trend for reduced maternal body weight was found on gd 11 and 15 with the value for the GV-10.0 group significantly different from controls on gd 11. A significant trend toward reductions in maternal weight gain for the gestation period, treatment period and absolute weight gain (weight gain during gestation minus gravid uterine weight) were found with the values for these three parameters in the GV-10.0 group significantly below those of controls. Weight gain during the treatment period was also significantly reduced in the GV-5.0 group versus controls. Clinical signs of toxicity presented a dose-response pattern, and included the following: weight loss of more than 5 grams in 24 hours, wheezing, lethargy, weakness, diarrhea, lacrimation and rough coat.

There were no dose-related differences observed in the following reproductive measures: number of implantation sites per litter; number or percent of resorptions, fetal deaths or non-live (dead plus resorptions) per litter. Among live litters, the number of live fetuses per litter, number or percent males per litter, average fetal body weight, average male or female fetal body weight per litter were also unaffected by treatment. There was a significant trend toward an increased number and percent affected (non-live plus malformed) per litter with dose; the number of litters with affected fetuses was significantly elevated in the GV-10.0 group versus controls. There were no gross malformations observed in any dose group in the study. Major visceral malformations observed included hydronephrosis (left or right) and hydroureter (unilaterally or bilaterally) with some fetuses exhibiting both malformations. Skeletal defects observed consisted mainly of short rib involving the thirteenth rib uni- or bilaterally. When incidence of all malformations were analyzed, there was a significant trend across dose groups toward increased number and percentage of fetuses, males, and females malformed per litter. In pairwise comparisons, the number and percentage of fetuses malformed per litter was significantly elevated in the GV-10.0 group versus controls as was the number of litters with malformed fetuses.

In conclusion, GV caused an increase in hydroureter, hydronephrosis and short ribs, the incidence being significant only in the GV-10.0 dose group. These malformations were accompanied by signs of maternal toxicity: reduction in maternal weight on gd 11, maternal weight gain during gestation and treatment periods, absolute weight gain and clinical signs. There was no significant incidence of malformations in the lower dose groups, in the absence of maternal toxicity (GV-2.5) or in the presence of limited maternal toxicity (GV-5.0). Hence, the fetal response to GV may be due in part to the compromised status of the dam.