The reproductive toxicology of intravenously administered MnDPDP in the rat and rabbit

Abstract

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. injections of MnDPDP. The developmental toxicity in rats was investigated after repeated daily i.v. injections during organogenesis with MnDPDP, MnCl₂, or DPDP, as well as with MnCl₂, administered orally. The developmental toxicity of i.v. injected MnDPDP was also investigated in rabbits.

Results: MnDPDP (100 μmol/kg) had no adverse effects on rat fertility. However, both MnDPDP (10–40 μmol/kg) and MnCl₂ (30 μmol/kg) caused skeletal abnormalities in the rat, but not in the rabbit given 20 μmol MnDPDP/kg. Maternal treatment of rats with MnDPDP (40 μmol/kg) reduced survival and body weights of neonates, and adversely affected their functional, but not physical development. No skeletal abnormalities were seen in the rat after i.v. administered DPDP (40 μmol/kg) or MnCl₂ (6 μmol/kg), or after MnCl₂ (400 μmol/kg) given by oral gavage. Maternal toxicity was not seen in rats or rabbits given these 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 the rat.