Effects of nonachloropredioxin and other hydroxychlorodiphenyl ethers on biological membranes

Abstract

Effects of the chlorophenolic compounds‐hydroxynonachlorodiphenyl ethers (HO‐CI₉‐DPEs), contaminants (1–5%) of commercial pentachlorophenol preparations; 2‐hydroxy‐2’,4,4'‐trichlorodiphenyl ether (HO‐Cl₃‐DPE); and pure and technical pentachlorophenol (PCP)‐on biological membranes have been studied with the human erythrocyte membrane as a model. The HO‐CI₉‐DPEs are very potent hemolytic agents. The order of activity, based on the concentration of compound producing 50% hemolysis (shown in parentheses), under standard conditions is: 2‐H0‐CI,‐DPE (3.8 μM) > 3‐HO‐CI₉‐DPE (7.1 μM)>4‐HO‐CI₉‐DPE (8.4 μM) > 2‐HO‐Cl₃‐DPE (68 μM) > technical PCP (360 μM) > pure PCP (950 μM). Among the HO‐Cl_x‐DPEs, the hemolytic potency varies with the degree of chlorination and, to some extent, with the position of the hydroxyl group. At lower concentrations, HO‐Cl_x‐DPEs protect the erythrocyte against hypotonic hemolysis; these compounds are effective at much lower concentrations than is pure PCP. In the range of concentrations required for maximum protection against hypotonic hemolysis, the chlorophenolic compounds induce the formation of erythrocyte morphological forms different from the normal discocyte. The chlorophenolic compounds induce the prelytic efflux of K⁺, from intact erythrocytes in an order of efficacy that parallels their hemolytic effect. These results show that the hydroxychlorodiphenyl ethers are membrane‐active chemicals, capable of directly altering properties of biological membranes.