The acute toxicity of Bimida, a prospective hepatobiliary scanning agent.
The acute toxic effects of dimethyl benzimidazolyl methyliminodiacetic acid (Bimida), a prospective hepatobiliary scanning agent when labelled with 99mTc, are described. The LD50 in male and female rats was 150 mg/kg, and in mice 100 mg/kg, males, and 75 mg/kg, females, up to 2000 times the diagnostic dose required in patients. Clinical signs associated with administration of lethal and sublethal doses of Bimida suggested the cause of death to be an acute hypocalcaemic episode; this was confirmed in vivo and in vitro. A significant reduction in alkaline phosphatase (ALP) activity and Ca2+ concentration associated with administration of 100 human equivalent doses (HED) Bimida and 99mTc labelled Bimida was measured in serum and microsomal preparations of liver and intestine. An in vitro system indicated that this response was prevented in the presence of adequate Ca2+, suggesting that ALP activity is depressed because chelation of the metal ion by Bimida causes a shortage of the Ca2+ needed to activate the enzyme.
D000818:Animals; D001659:Biliary Tract / Q000000981:diagnostic imaging*; D002118:Calcium / Q000097:blood; D005260:Female; D007098:Imino Acids / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000000981:diagnostic imaging*; D008297:Male; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D013667:Technetium / Q000633:toxicity*
D007098:Imino Acids; D015609:Organotechnetium Compounds; C044973:technetium Tc 99m benzimidazolyl iminodiacetic acid; D013667:Technetium; D002118:Calcium