THE REPRODUCTIVE TOXICOLOGY OF INTRAVENOUSLY ADMINISTERED MNDPDP IN THE RAT AND RABBIT

Purpose: The reproductive toxicology of mangafodipir trisodium (MnDPDP , Teslascan), a new hepatobiliary MR contrast agent, was evaluated in rats and rabbits. Material and Methods: Male and female fertility and post-natal development were examined in rats after repeated i.v. injec tions of MnDPDP. The developmental toxicity in rats was investigated a fter repeated daily i.v. injections during organogenesis with MnDPDP, MnCl2, or DPDP, as well as with MnCl2 administered orally. The develop mental toxicity of i.v. injected MnDPDP was also investigated in rabbi ts. Results: MnDPDP (100 mu mol/kg) had no adverse effects on rat fert ility. However, both MnDPDP (10-40 mu mol/kg) and MnCl2 (30 mu mol/kg) caused skeletal abnormalities in the rat, but not in the rabbit given 20 mu mol MnDPDP/kg. Maternal treatment of rats with MnDPDP (40 mu mo l/kg) reduced survival and body weights of neonates, and adversely aff ected their functional, but not physical development. No skeletal abno rmalities were seen in the rat after i.v. administered DPDP (40 mu mol /kg) or MnCl2 (6 mu mol/kg), or after MnCl2 (400 mu mol/kg) given by o ral gavage. Maternal toxicity was not seen in rats or rabbits given th ese doses. Conclusion: MnDPDP caused skeletal abnormalities in foetal rats, but not rabbits, and had no effects on rat fertility. Manganese appears to be the causative agent for inducing bone abnormalities in t he rat.