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

Abstract

Subchronic 90-day feeding studies were conducted in male and female (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.

Scientific Opinion on Mineral Oil Hydrocarbons in Food

“…of P15(H) white oil. The hydrocarbon concentration in blood and liver was analysed by GC/GC-MS and quantified based on the C 19 -C 24 range of alkanes present in P15(H) white oil (Cnubben and van Stee, 2010 Smith et al, 1996) and 1 500 mg/kg b.w. resulted in similar calculated maximum blood concentrations of approximately 14 and 15 g/ml, respectively.…”

“…As compared with the liver, the hydrocarbon concentration in mesenteric lymph nodes was approximately 2-3 and 5 fold lower for Sprague Dawley and Fischer 344 strains, respectively. Smith et al (1996) performed a 90-day feeding study in male and female Fischer 344 rats with seven different white oils (Figure 23). In the liver, saturated hydrocarbon contents ranged from 0.6 to 4.3 mg/g tissue in female rats fed a diet containing 20 g /kg mineral oils, and were 4-5 times greater than in males (exact data in males not reported by the authors).…”

“…Levels in the spleen and kidney were much lower and did not exceed 0.1 mg/g tissue. Smith et al (1996).…”

“…However, for the most part this effect was found to be unique to Fischer 344 rats (Baldwin et al, 1992;Firriolo et al, 1995;Smith et al, 1996;Griffis et al, 2010). The liver microgranulomas induced in Fischer 344 rats are associated with T and B lymphocyte influx and sometimes with central necrosis and fibrosis.…”

Effect Of Ginger Extract On Gasoline Associated Immunitoxicities In Wistar Rats

“…Also, reduction of met hemoglobin to hemoglobin requires NADPH, which is generated through pentose phosphate pathway, and nitrate inhibits the enzyme, glucose-6-phosphate dehydrogenase in the erythrocytes, resulting in increased methemoglobin (Ovuru and Ekweozor, 2004). The toxicity of benzene could involve inhibition of the hematopoietic component in the bone marrow, causing depression of the bone marrow, spleen, and lymph nodes, leading to leukemia, and bone marrow hypoplasia (Marieb,1995;Rabble and Wong,1996;Smith et al ,1996;d'Azevedo et al,1996;Ross,1996;Rothman et al,1996). The resultant bone marrow depression is characterized by inadequate production of red blood cells and white cells (Rabble and Wong, 1996).…”