Dose-response immunotoxicities of commercial polychlorinated biphenyls (PCBs) and their interaction with 2,3,7,8-tetrachlorodibenzo-p-dioxin

Abstract

The relative potencies of the commercial polychlorinated biphenyl (PCB) mixtures Aroclors 1260, 1254, 1248, 1242, 1016 and 1232 to inhibit the murine splenic plaque-forming cell response to sheep red blood cells was determined by dose-response treatment of C57BL/6 mice followed by logit plot analysis of the data. The ED50 values obtained for Aroclors 1260, 1254, 1248, 1242, 1016 and 1232 were 104, 118, 190, 391, 408 and 464 mg/kg or 0.28, 0.35, 0.66, 1.5, 1.5 and 2.0 mmol/kg, respectively. It was apparent that the higher chlorinated PCB preparations (Aroclors 1260, 1254 and 1248) were more potent than the lower chlorinated preparations (Aroclors 1242, 1016 and 1232). Previous studies have shown that the interaction of a subeffective dose of Aroclor 1254 (25 mg/kg) with an immunotoxic dose (3.7 nmol/kg) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in significant antagonism of the toxicity of the latter compound. Co-treatment of mice with a 25 mg/kg dose of all the commercial Aroclors and with a 50 mg/kg dose of a reconstituted PCB mixture (resembling a PCB extract from human milk) with TCDD (3.7 nmol/kg) showed that, with the exception of Aroclor 1232, all of the commercial PCBs and the reconstituted PCB mixture significantly antagonized the TCDD-mediated inhibition of the splenic plaque-forming cell response in C57BL/6 mice. The identities of the PCB congeners responsible for this antagonism and the mechanism of this process are unknown and are currently being investigated.