Liver morphology in guinea pigs fed pyrolysis products of a polychlorinated biphenyl transformer fluid continuously for 90 days.

After a fire involving a transformer, the State Office Building in Binghamton, New York, was contaminated with soot containing polychlorinated biphenyls, biphenylenes, naphthalenes, dioxins, and dibenzofurans. The toxicity of the soot and its effect on liver morphology after prolonged (subchronic) exposure were determined for both sexes of Hartley guinea pigs, which were fed soot continuously for 90 days. By light microscopy the observed alterations of the liver were predominantly centrilobular; they included hepatocyte hypertrophy, steatosis, increased glycogen and iron, focal necrosis, and bile duct proliferation with fibrosis. Cytoplasmic vacuoles and acidophilic hyalin-like bodies were observed. Electron microscopy of hepatocytes showed proliferated smooth endoplasmic reticulum (SER), cytoplasmic vacuoles, concentric membrane arrays (CMAs), glycogen bodies, and microdroplets of fat, often without limiting membranes. The vacuoles frequently contained membrane fragments and had a halo-like periphery composed of proliferated membranes. Cell debris, membrane fragments, and small CMAs were observed in the sinusoids. Membrane fragments were also observed in the bile canaliculi and bile ducts. Intoxicated bile duct cells contained more cytoplasmic myelin whorls and altered mitochondria. In contrast to the previously reported study of a single dose, these liver alterations showed a strong dose dependence, emphasizing the importance of time and method of administration. The cytoplasmic vacuoles, which were not pronounced in the previous study, are here a prominent alteration, probably originating from outpouchings of canaliculi and sinusoidal membranes. A hypothesis for the mechanism of hepatocyte detoxification based on the proliferated SER and ejection of membrane fragments is proposed.