Kinetics and toxic effects of repeated intravenous dosage of formic acid in rabbits.
Adult male rabbits were injected i.v. with 100 mg buffered formic acid per kg body weight daily for 5 days with 24 h between the doses. The fifth dose was labelled with 14C-formic acid. Rabbits were killed 1, 2 and 20 h after the last injection. The highest formic acid concentrations were found one hour after the fifth dose. Total formic acid concentrations were always higher than radiometrically measured. The maximum concentrations of formic acid in brain, heart, kidney and liver were roughly similar to the concentration which inhibits half of the cytochrome oxidase activity in vitro. Histological studies clearly demonstrated the histotoxic changes at cellular level. Calcium deposits were detected in all organs of the injected rabbits. They were absent in control animals. It seems that the formic acid metabolism is slow and that it may cause sufficient hypoxic acidosis to allow the calcium influx and cellular damage.
Kuopio Regional Institute of Occupational Health, Finland.
J
J
Liesivuori
V M
VM
Kosma
A
A
Naukkarinen
H
H
Savolainen
D000138:Acidosis / Q000139:chemically induced; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000032:analysis; D005561:Formates / Q000493:pharmacokinetics* / Q000633:toxicity; D006651:Histocytochemistry; D000860:Hypoxia / Q000139:chemically induced; D007275:Injections, Intravenous; D007668:Kidney / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000032:analysis / Q000378:metabolism; D011817:Rabbits
D005561:Formates; C030544:formic acid; D002118:Calcium