The toxicity of parenteral copper in the chick: dependence on route of administration

Preliminary work in our laboratory suggested that the route of parenteral copper administration influences the acute toxicity of copper (Cu). The present work examined the effects of Cu given either intraperitoneally (i.p.) or intravenously (i.v.) on mortality, feed intake, peritoneal fluid and hepatic accumulation of Cu and zinc (Zn) in chicks. We also studied the potential interaction of prior Zn loading on these parameters. Four-wk-old chicks were pretreated by injection (subcutaneous) with Zn acetate (5 mg Zn/kg) or sodium acetate 24 h prior to Cu treatments. Copper as Cu acetate was given either i.p. or i.v. at a dose of 1.84 mg Cu/kg. Mortality was markedly greater in those chicks given Cu i.p. compared to those given Cu i.v. (46.1% vs. 3.9%). Zinc pretreatment had no effect on any of the parameters associated with copper treatments. The accumulation (24 h) of copper in either total hepatic tissue or cytosol was comparable for both routes of injection. However, marked differences in Cu-induced hepatic Zn accumulation were observed. Massive peritoneal fluid (41% of total plasma volume) was observed 1 to 3 h following the administration of Cu i.p. None was observed in those given Cu i.v. Thus, this effect was associated with the route-dependent mortality observed in the present study. We suggest that our data highlight the gratuitous effects of reactive agents given intraperitoneally.