The reproductive toxicology of intravenously administered MnDPDP in the rat and rabbit.
OBJECTIVE
The reproductive toxicology of mangafodipir trisodium (MnDPDP, Teslascan), a new hepatobiliary MR contrast agent, was evaluated in rats and rabbits.


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 mumol/kg) had no adverse effects on rat fertility. However, both MnDPDP (10-40 mumol/kg) and MnCl2 (30 mumol/kg) caused skeletal abnormalities in the rat, but not in the rabbit given 20 mumol MnDPDP/kg. Maternal treatment of rats with MnDPDP (40 mumol/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 mumol/kg) or MnCl2 (6 mumol/kg), or after MnCl2 (400 mumol/kg) given by oral gavage. Maternal toxicity was not seen in rats or rabbits given these doses.


CONCLUSIONS
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.
Grant
D
D
Nycomed Imaging AS, Oslo, Norway. dgr@nycomed.com
Blazak
W F
WF
Brown
G L
GL
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008345:Manganese / Q000008:administration & dosage; D020149:Manganese Poisoning; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D003287:Contrast Media; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid