Pulmonary histopathology of rats following parenteral injections of nickel chloride.
To elucidate the subacute toxic reactions to parenteral administration of Ni2+, male F-344 rats were given daily injections of NiCl2 (62.5 or 125 mumol/kg, sc) for 3 to 6 weeks. Nickel accumulation was greater in lung than in the other major organs, based upon tissue analyses by electrothermal atomic absorption spectrometry. After 5 or 6 weeks of NiCl2 treatment, severe pathological changes developed in the lungs, including a) prominent hydropic and degenerative changes of the endothelium of pulmonary arteries and veins; b) marked proliferation of alveolar lining cells, affecting Type II (granular)pneumocytes; c) thickening of alveolar walls, with proteinaceous alveolar exudate; d) hyperplasia of bronchial epithelium, with cellular atypia and mitoses; and e) focal bronchial pneumonia with intrabronchial exudates. These pulmonary responses to repeated daily injections of NiCl2 were substantially different from the pathological lesions seen 24 to 72 hours after a single sc injection of NiCl2 (500 or 750 mumol/kg), which included perivascular edema, karyorrhexis and pyknosis of mononuclear cells in focal perivascular infiltrates, and mild pulmonary congestion. This study shows that the lung is a primary site of toxicity in rats following parenteral administration of NiCl2; vascular endothelial cells, Type II pneumocytes, bronchial epithelial cells, and mononuclear cells constitute the principal cellular targets for pulmonary toxicity of Ni2+.
Knight
J A
JA
Department of Laboratory Medicine, University of Connecticut School of Medicine, Farmington 06032.
Rezuke
W N
WN
Gillies
C G
CG
Hopfer
S M
SM
Sunderman
F W
FW
D000818:Animals; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
C022838:nickel chloride; D009532:Nickel