Comparative toxicity study of 2,4,5,2′,4′,5′-hexachlorobiphenyl and a polychlorinated biphenyl mixture in rabbits

Abstract

Three groups of rabbits were treated daily (5 times per week for 28 days) with 120 mg 2,4,5,2′,4′,5′-hexachlorobiphenyl, 120 mg polychlorinated biphenyl (PCB) mixture (Aroclor 1260 ®) and the solvent isopropanol, respectively. The dermal application resulted in early macroscopic skin lesions in the Aroclor group. The lesions in the 2,4,5,2′,4′,5′-hexachlorobiphenyl group appeared later on and were less severe. This difference was confirmed microscopically: hyperplasia and hyperkeratosis of the follicular and epidermal epithelium were more severe in the Aroclor ® group. Fecal coproporphyrin levels were significantly increased in the experimental groups. Enhanced liver weights were found in both test groups. Liver injury, as judged by light microscopic lesions and elevated serum transaminase levels, was somewhat more severe in the hexachlorobiphenyl group when compared with the Aroclor ® group, though the mean liver content was about the same (respectively, 239 and 236 ppm). Light microscopic findings included subcapsular necrosis, zonal necrosis, hydropic degeneration, as well as a peripheral and perinuclear shift of cell organelles, and focal cytoplasmic hyalin degeneration. In electron microscopy the shift was found to be due to a proliferation of smooth surfaced membranes of the endoplasmic reticulum (SER), resulting in a displacement of rough surfaced membranes (RER) and mitochondria. The hyalinized cytoplasm was recognized as tightly packed tubules of proliferated SER, that is considered as hypertrophic, hypoactive SER. The contribution of chlorinated dibenzofurans and pure PCB in the toxicity of crude PCB mixtures is discussed.