METABOLIC ACIDOSIS AND HYPOCALCEMIA AS TOXIC MANIFESTATIONS OF POLYMERIC PHOSPHATES

¹ Department of Pharmacology, University of Rochester Atomic Energy Project, Rochester, N. Y.
² Lt., MC, Chemical Corps Med. Lab., Army Chemical Center, Md.
³ Dept. of Biochemistry, University of Wisconsin, Madison, Wisconsin

Two severe biochemical disturbances have been identified in rats after the parenteral administration of a short-chain linear polymer of sodium phosphate (Na-HMP); they are (a) a reduction in the plasma concentration of ionized calcium and (b) a metabolic acidosis. Hypocalcemia was due to the formation in vivo of a chelate-complex between Ca⁺⁺ and the HMP anion. Acidosis resulted from the enzymatic hydrolysis of the polymer into orthophosphoric acid residues. As identified by characteristic changes in the electrocardiogram, hypocalcemia could be detected when the sodium polymer (Na-HMP) was given by the intravenous route only, in which case cardiac arrest promptly occurred. A systemic metabolic acidosis resulted whatever the parenteral route of administration. As judged by reductions in the content of CO₂ in arterial plasma, this acidosis was regarded as a major cause of death after intraperitoneal doses of Na-HMP in the rat. Similar conclusions were reached with sodium tripolyphosphate. Sodium pyrophosphate owed its relatively high toxicity to its ability to evoke hypocalcemia, even by the intraperitoneal route. Least toxic were the stable compounds, ortho-, trimeta-, and tetrametaphosphate, which produced neither acidosis nor hypocalcemia. Using Ca⁴⁵, measurements were made of the relative stability of the calcium complexes formed in vitro.