Granulomas in the livers of humans and Fischer rats associated with the ingestion of mineral hydrocarbons: a comparison.
Ninety-day feeding studies were conducted in Fischer 344 rats using a series of highly refined mineral hydrocarbons which included mineral oils and waxes representative of those used in consumer products and food applications. The series included materials which had been refined by oleum or hydrogenation. The materials tested were representative of the range of carbon chain lengths, molecular weights, and viscosities which are currently in use. Findings revealed the presence of granulomatous lesions in the liver and histiocytosis in the lymph nodes. Some mineral hydrocarbons did not induce any lesions; others induced relatively minor effects; and a low melting point wax induced the largest lesions in both liver and mesenteric lymph nodes, with inflammation and areas of focal necrosis in the livers. The majority of lesions reported were associated with the highest dose levels used. These studies are in contrast to studies in Sprague-Dawley rats in which comparable doses did not induce similar lesions, indicating marked strain variability. Lipogranulomas associated with the ingestion of mineral oil have been reported in humans. The comparative morphology of the lesions seen in the Fischer rat study and those observed in the human are discussed and differences are highlighted. The lesions in the human are not believed to progress to lesions of clinical significance. The pathogenesis of the lesions induced in Fischer rats and in humans is discussed and it is concluded that the majority, if not all of the lesions, in the rats are of no significance for humans. The possibility that a small proportion of cases of granulomatous hepatitis in humans may represent an atypical response to mineral hydrocarbons may need further investigation.
Fleming
K A
KA
Green College, Radcliffe Observatory, Oxford, United Kingdom.
Zimmerman
H
H
Shubik
P
P
D000821:Animal Feed / Q000009:adverse effects; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004032:Diet / Q000009:adverse effects; D006099:Granuloma / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006349:Heart Valve Diseases / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D006801:Humans; D006838:Hydrocarbons / Q000009:adverse effects*; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008206:Lymphatic Diseases / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D008899:Mineral Oil / Q000009:adverse effects / Q000032:analysis; D008943:Mitral Valve / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
D006838:Hydrocarbons; D008899:Mineral Oil