PHARMACOLOGIC OBSERVATIONS ON TWO QUATERNARY AMMONIUM GERMICIDES

¹ Departments of Pharmacology and Bacteriology, Medical College of Virginia, Richmond, and Pathology Laboratory, Chesapeake and Ohio Hospital, Clifton Forge, Virginia

1. The acute oral, intraperitoneal and intravenous LD₅₀'s for Hyamine 1622 (di-isobutyl-phenoxy-ethoxy-ethyl-dimethylbenzyl ammonium chloride) and Hyamine 2389 (alkyl-(C-9 to C-15)-tolyl-methyltrimethyl ammonium chlorides) have been determined in rats.

2. When incorporated in the diet of rats for a two-year period both Hyamines affected survival at a level of 5000 p.p.m. but not at 2500 p.p.m. Hyamine 2389 inhibited growth at both of these levels whereas Hyamine 1622 reduced growth rate only at the 5000 p.p.m. level. Hematologic findings were within normal limits. No microscopic pathologic changes were seen other than testicular atrophy in a few of the animals fed 2500 and 5000 p.p.m. Hyamine 1622 for 23 months. Gross pathologic changes were limited to the cecum which was distended at levels of 1000 p.p.m. or above of either compound. Moisture content of the cecal material and feces was significantly increased at levels of 2500 p.p.m. and higher after four days of feeding. At the 2500 and 5000 p.p.m. levels a marked reduction in Gram-positive cecal and fecal flora occurred and was accompanied by a relative increase in Gram-negative flora. Blood culture studies on moribund animals were negative.

3. Neither Hyamine appeared to cause ill effects when fed to dogs for one year at levels up to 500 p.p.m. in the diet in that no effects were seen on growth, blood picture, incidence of pathologic changes or survival.

4. Both Hyamines inhibited the motility of isolated rabbit and rat ileum in concentrations as low as 0.002 per cent.

5. Both Hyamines produced nearly complete sympathetic ganglionic blockade, as judged by blood pressure studies in the dog, at an intravenous dose of 2 mgm./kgm.

6. Hyamine 1622 was not irritant to the conjunctiva of the rabbit eye in concentrations up to 0.01 per cent. With Hyamine 2389 the maximal non-irritant concentration was 0.03 per cent.

7. Rabbits to which 0.1 per cent Hyamine 1622 or 0.05 per cent Hyamine 2389 solutions had been applied to the skin daily for four weeks showed no gross or microscopic signs of local or systemic toxicity.

8. As shown by patch tests on man, Hyamine 2389 may be irritating to the skin at concentrations of 10 per cent or above; no sensitization developed.