DEVELOPMENTAL TOXICITY OF DIETARY ZINC-DEFICIENCY IN NEW-ZEALAND WHITE-RABBITS

Chemically induced maternal Zn deficiency has been shown previously to cause terata and increase embryonic loss in rodents, To examine the p otential effects of Zn deficiency in the rabbit, a major developmental toxicity test species, rabbit dams were fed an ethylenediamine-tetraa cetic acid-washed alfalfa-based Zn-deficient diet (-Zn) or the same di et replete with 80 ppm Zn (control) from Gestation Day (GD) 0 through 20, A third group of animals was pair fed to match the mean daily feed consumption levels of the <2 ppm Zn group, By GD 7, maternal serum Zn levels of the -Zn dams were decreased 56% and reached a nadir with a 75% decrease of serum Zn by GD 14, Zinc concentrations in the visceral yolk sac and visceral yolk sac-exoceolomic fluid were decreased 30% a nd 50%, respectively, by GD 11, Although GD 11 embryonic Zn levels wer e not affected, the embryos from Zn-deficient dams exhibited decreased head length, somite number, and total protein, On GD 28, a significan t increase in resorptions/litter was noted in the -Zn group, and the i ncidence of totally resorbed litters of the -Zn group was greater than laboratory historical control values, No terata were observed in GD 2 8 fetuses, This study indicates that Zn deficiency occurring during th e standard dosing period of guideline rabbit developmental toxicity st udies may be associated with a modest increase in resorption rate and a transient inhibition of embryonic growth, but in contrast to rodent species, does not appear to be teratogenic. (C) 1997 Elsevier Science Inc.