Immunotoxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in a Complex Environmental Mixture from the Love Canal

Immunotoxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in a ComplexEnvironmental Mixture from the Love Canal. SILKWORTH, J. B.,CUTLER, D. S., AND SACK, G. (1989). Fundam. Appl Toxicol. 12,303-312.The organic phase ofthe leachate (OPL) from the Love Canal chemicaldump site contains more than 100 organic compounds including2,3,7.8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxicpotential of OPL was determined in two mouse strains which differin their sensitivity to aromatic hydrocarbon (Ah) receptor-mediatedtoxicity. OPL was administered in corn oil in a single oralgavage to male BALB/cByJ (Ah^b/Ah_b) mice (0.5, 0.8, or 1.1 g/kg)and DBA/2J (Ah^b/Ah_b) mice (0.6, 0.9, or 1.3 g/kg). TCDD wassimilarly administered at 0.25, 1.0, 4.0, or 16.0 µg/kg.Two days later all mice were immunized with sheep erythrocytes(SRBC). The antibody response (PFC) and organ weights were evaluated4 days later. OPL produced thymic atrophy and hepatomegaly inboth strains at all dose levels. The PFC/spleen in BALB/cByJmice was significantly reduced at the three doses to 34, 13,and 15%, respectively, of the control response. Serum anti-SRBCantibody levels and relative spleen weights were also reduced.The only immune effect in the DBA/2J mice was a decrease ofthe PFC/spleen to 58% of the control at the highest dose. TCDDdecreased the relative thymus and spleen weights only in BALB/cByJmice. However, TCDD produced hepatomegaly, a decrease in serumantibody, and a decrease in PFC/spleen in both BALB/cByJ andDBA/B mice to 3 and 15%. rspectively, at 16 µg/kg. Thus,the TCDD dose required to cause a 50% suppression (ED50) ofPFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and3.89 µg/kg, respectively. The ED50 for OPL was 0.24 g/kgin BALB/cByJ mice. The TCDD concentration in the OPL was estimatedto be 7.6 ppm, which agrees closely with the chemical analysis(3 ppm). The results suggest that the immunosuppression causedby OPL in BALB/cByJ mice was primarily due to TCDD. that thenon-TCDD components of OPL diminished the TCDD immunotoxicityin the DBA/2J strain, and that the thymic atrophy and hepatomegalywere caused primarily by the non-TCDD components of the OPL.