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Ninety-Day Feeding Study in Fischer-344 Rats of Highly Refined Petroleum-Derived Food-Grade White Oils and Waxes

Exxon Biomedical Sciences, Inc., East Millstone, New Jersey 00875-2350, USA

Anthony K. Mallett

BP International Limited, Surrey GU2 5YQ, United Kingdom

Robert A.J. Priston

Shell Internationale Petroleum Maatschappij B. V., 2501 AN The Hague, The Netherlands

Paul G. Brantom

BIBRA Toxicology International, Woodmansterne Road, Carshalton, Surrey SM5 4DS

Nan R. Worrell

BIBRA Toxicology International, Woodmansterne Road, Carshalton, Surrey SM5 4DS

Christine Sexsmith

American Petroleum Institute, Washington, D.C. 20005, USA

Barry J. Simpson

CONCAWE (The Oil Companies' European Organisation for Environmental and Health Protection), B-1030 Brussels, Belgium

Subchronic 90-day feeding studies were conducted in male and female Fischer-344 (F-344) rats on highly refined white mineral oils and waxes representative of those used for food applications. The goal was to help clarify the mixed results found in other toxicity studies with laboratory animals. Seven white oils and 5 waxes were fed at dietary doses of 20,000, 2,000, 200, and 20 ppm and compared with control groups on untreated diet; toxicity was assessed at 90 days and also after a reversal period of 28 days and/or 85 days. Higher molecular-sized hydrocarbons (microcrystalline waxes and the higher viscosity oils) were without biological effects. Paraffin waxes and low- to midviscosity oils produced biological effects that were inversely related to molecular weight, viscosity, and melting point; oil type and processing did not appear to be determinants. Biological effects were more pronounced in females than in males. Effects occurred mainly in the liver and mesenteric lymph nodes and included increased organ weights, microscopic inflammatory changes, and evidence for the presence of saturated mineral hydrocarbons in affected tissues. Inflammation of the cardiac mitral valve was also observed at high doses in rats treated with paraffin waxes. Further studies are required to elucidate the mechanism for the responses observed and the relevance of these inflammatory responses in the F-344 rat to other species, including humans.

Key Words: Cardiac mitral valve • food-grade mineral hydrocarbons • granuloma • inflammatory response • liver • macrophage accumulation • mesenteric lymph nodes

Toxicologic Pathology, Vol. 24, No. 2, 214-230 (1996)
DOI: 10.1177/019262339602400210


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