EFFECTS OF ORALLY ADMINISTERED THIAMINE TETRAHYDROFURFURYL DISULFIDE ON FOETAL DEVELOPMENT OF RABBITS AND MONKEYS

Abstract

In vitro studies with thiamine tetrahydrofurfuryl disulfide (TTFD) revealed that treatment of the fertilized sea urchin ova produced arrest of cellular division at the metaphase stage (1). It was postulated that this was probably due to interference with interconversion of thiol disulfide responsible for the mitotic mechanism (1, 2). The depressant effect of TTFD on cellular proliferation has also been demonstrated in primary monolayer culture of chick heart cells, hamster and monkey kidney cells (3) and amnion (4) and kidney cells of the human embryo (5).
It has also been shown that in experimental animals (rats and rabbits) there is a more marked accumulation of TTFD in circulating erythrocytes and tissue cells than thiamine (6) and that, in pregnant mice, TTFD•HCl crosses the placental barrier into the foetus (7).
Despite the possible implications of these findings to embryonic development, daily oral administration of TTFD•HCl at 30 and 300 mg/kg (equivalent to 5 to 10 and 50 to 100 times the maximum human therapeutic dosage) to pregnant CF-1 mice and SD rats during the critical stages of organ differentiation failed to produce any significant developmental abnormality (8).
The present report deals with subsequent teratological studies of TTFD•HCl, performed in the rabbit and in the cynomolgus monkey.