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 potential effects of Zn deficiency in the rabbit, a major developmental toxicity test species, rabbit dams were fed an ethylenediamine-tetraacetic acid-washed alfalfa-based Zn-deficient diet (-Zn) or the same diet 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% and 50%, respectively, by GD 11. Although GD 11 embryonic Zn levels were not affected, the embryos from Zn-deficient dams exhibited decreased head length, somite number, and total protein. On GD 28, a significant increase in resorptions/litter was noted in the -Zn group, and the incidence of totally resorbed litters of the -Zn group was greater than laboratory historical control values. No terata were observed in GD 28 fetuses. This study indicates that Zn deficiency occurring during the standard dosing period of guideline rabbit developmental toxicity studies 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.
Pitt
J A
JA
Developmental and Reproductive Toxicology, Health and Environmental Research Laboratory, Dow Chemical Company, Midland, Michigan, USA.
Zoellner
M J
MJ
Carney
E W
EW
D000818:Animals; D020964:Embryo Loss / Q000209:etiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D008070:Lipopolysaccharides; D011247:Pregnancy; D011817:Rabbits; D015032:Zinc / Q000097:blood / Q000172:deficiency*
D008070:Lipopolysaccharides; D015032:Zinc