Embryonal disposition of salicylate: in vivo-in vitro comparisons.

The distribution of salicylate to embryonal compartments for in situ and in vitro rat embryos under equivalent exposure conditions, and salicylate disposition in the in vivo mid-gestation embryo and late gestation fetus, were compared. Pregnant Sprague-Dawley CD rats were exposed to steady-state blood levels of salicylate by infusing 14C-salicylic acid iv for a 24 hour period from gestation day 11.5 to 12.5. Cultured Sprague-Dawley rat embryos (in medium consisting of 100% male rat serum) were exposed to the steady-state 14C-salicylate concentration achieved in maternal serum in vivo for the same 24 hour developmental period. At the end of the exposure period radioactivity in visceral yolk sac, extra-embryonic fluid and embryos, and in maternal tissues, was measured. The distribution of salicylate to embryonal tissues was statistically comparable in vivo and in vitro, although the embryos in vitro accumulated slightly (but not significantly) less of the chemical. There was considerable binding of salicylate by maternal serum and culture medium proteins: less than 20% of the chemical was free at the 40 micrograms/ml concentration used in this experiment. Consequently, the salicylate concentration in embryonal compartments appeared to be quite low when compared to the surrounding serum/medium, but was actually equal to or greater than the concentration of unbound salicylate in serum or culture medium. The proportion of free salicylate in serum increased at concentrations higher than 40 micrograms/ml, resulting in somewhat higher concentrations of salicylate in in vitro embryos and extraembryonic fluid (as compared to medium) when cultured in the presence of 200 or 400 micrograms/ml salicylate.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of dietary iron supplementation on the toxicity of piroctone olamine in the growing rat.

Weanling Charles River CD rats of both sexes were fed 300 mg/kg/day of Piroctone Olamine, an anti-bacterial agent, and were supplemented with 0, 50, 100 or 200 ppm dietary iron as FeSO4.7H2O for six weeks. However, analytical data indicated that Piroctone was degraded in the diet so that the rats received only 225 mg/kg/day. The rats given Piroctone Olamine without iron gained significantly less body weight and ate significantly less feed than controls, with the effect being more pronounced in the males. They also developed severe microcytic, hypochromic anemia. The rats supplemented with all three levels of dietary iron grew at a rate similar to controls. The rats supplemented with 50 ppm dietary iron had anemia with all of the hematological iron-associated factors being significantly depressed. The 100 ppm supplement restored all hematologic factors to normal in the females, but slight reductions remained in the males. The 200 ppm supplement of iron restored all parameters to values similar to the controls in both sexes. These results suggest that the mechanism of the toxicity of Piroctone Olamine is the prevention of dietary iron absorption by in situ chelation.