Objective: To study the reproductive toxicity of metadoxine.
Methods: Male and female rats were given metadoxine before pregnancy and early gestation, i.e. to feed metadoxine to male rats for 60 days before copulation and continue feeding during copulation, and feed metadoxine to female rats for 14 days before copulation.
Results: No significant toxic effect was observed in the 400 mg/kg group. A few rats showed paralysis of hind leg in the 800 mg/kg group. The dosage of 1 600 mg/kg caused significant paralysis of hind legs, emaciation, and reduced weight gain. In the 1600 mg/kg group, the mating rate of male rats was significantly affected (P < 0.01). In the 800 and 1 600 mg/kg group, fertility of male rats was markedly reduced (P < 0.01). In the 800 mg/kg group, the effect on sperm counts of epididymis of male rats was markedly reduced (P < 0.05). In the 1 600 mg/kg group, testicle weight and body weight ratio and sperm counts of epididymis rate were significantly (P < 0.001) reduced. In the 1 600 mg/kg group, the fertility rate of female rats was remarkably (P < 0.001) reduced. In the 800 mg/kg group, the weight gain of pregnant rats was significantly reduced (P < 0.001). In both the 800 and 1 600 mg/kg groups, the gestation rate was greatly reduced (P < 0.001). In the 800 mg/kg group, mortality rate before nidation (P < 0.001) and average live fetus number were significantly reduced (P < 0.05). In the 400 mg/kg group, the fetal weight was significantly reduced (P < 0.001). In the 800 mg/kg group, body length, tail length, body weight and sternum development of fetal rats were significantly affected (P < 0.001).
Conclusion: Under the presented experimental conditions, metadoxine has no teratogenic effects on SD rats and the no effect dose is 400 mg/kg. And the no effect dose for the developmental toxicity is less than 400 mg/kg.