ACUTE HEPATOTOXICITY OF ETHYLENE, VINYL FLUORIDE, VINYL-CHLORIDE, AND VINYL BROMIDE AFTER AROCLOR 1254 PRETREATMENT

Male rats were pretreated by gavage with the polychlorinated biphenyl mixture (PCB) Aroclor 1254 (300 μmole of PCB/kg) for 3 consecutive days. On the fourth day these rats were exposed by inhalation (4 hr) to various concentrations of ethane, ethylene, fluoride monomer (VFM), vinyl chloride monomer (VCM), or vinyl bromide monomer (VBM). Animals were sacrificed 24 hr after exposure and acute hepatic responses were estimated by measurement of serum alanine-α-ketoglutarate transaminase (SAKT) and by light microscopy. All of the compounds tested, except ethane, caused significant elevations of SAKT and produced severe degeneration and necrosis of the liver. Typical SAKT values (milligrams of pyruvate per milliliter of serum per hour) were: absolute controls, 0.17 ± 0.01; PCB pretreated, not exposed, 0.19 ± 0.02; PCB and 50,000 ppm of ethane, 0.11 ± 0.02; PCB and 25,000 ppm of ethylene, 1.98 ± 0.61; PCB and 10,000 ppm of VFM 6.29 ± 0.99; PCB and 10,000 ppm of VCM 1.11 ± 0.32; and PCB and 33,000 ppm of VBM, 3.78 ± 2.28. The relative potencies of these compounds in elevating SAKT were similar and the spectrum of morphologic changes (e.g., midzonal ballooning of hepatocytes and centrolobular hemorrhagic necrosis) was the same. The acute hepatotoxicity of ethylene plus PCB and lack of effect from ethane plus PCB indicate a role for the double bond in these toxic interactions. With the exception of ethane the compounds tested are similar in acute toxicity after PCB pretreatment. This similarity of acute action, in light of the carcinogenicity of VCM, suggests that ethylene, VMF, and VBM should be evaluated for chronic effects. © 1978.