Teratogenic effects in rabbits of simultaneous exposure to ochratoxin A and aflatoxin B1 with special reference to microscopic effects

To elucidate the teratogenic effects, ochratoxin A (OTA) and aflatoxin B-1 (AFB(1)) were dissolved in corn oil and administered in combination to New Zealand White rabbits during 6-18 days of gestation orally with the dose levels of OTA + AFB(1), 0.05 + 0.05 and 0.1 + 0.1 mg/kg body weight. To assess pathomorphological features of the anomalies, the fetal serial sections were histologically examined. There was no mortality in any of the treated groups. Body weights and body weight gains of dams in the combined treatment groups were comparable with those of controls and individual treatments. The mean crown to rump lengths in both the combination dose groups and mean fetal weights in high dose combination group were significantly decreased. In the high dose combination, there was increase in the percent of implants resorbed and significant increase in the incidence of visceral anomalies. The combination treatment resulted in various gross, skeletal and visceral anomalies such as wrist drop, scoliosis, bent metacarpals, rudimentary ribs, cardiac defects and microphthalmia. There was a dose-related increase in the percent of litters showing the histopathological changes in the fetal tissues. The incidence of histopathological changes in the tissue sections prepared from fetal liver, kidneys, brain, heart and eyes was found increased in the high dose combination group. The comparative evaluation of the results of combination versus individual treatments revealed that certain anomalies observed in the individual treatment of OTA such as knuckling of fetlock, rudimentary tail or agenesis of tail, wavy ribs, hydrocephalus and agenesis of kidney and AFB(1) as enlarged eye sockets and enlarged liver were absent in the combination treatment. However, some new manifestations such as cardiac defects and scoliosis were seen. The results of the present study indicated that in combination, OTA and AFB(1) have antagonistic interaction. The presence of subtle lesions histologically due to an interference with normal development suggested that microscopic examination of the fetal tissues could provide additional, useful information to a developmental toxicity study. (c) 2005 Elsevier Ireland Ltd. All rights reserved.