Results of Chronic Dietary Toxicity Studies of High Viscosity (P70H and P100H) White Mineral Oils in Fischer 344 Rats

Abstract

Two-year dietary studies were conducted to determine the chronic toxicity and its reversibility, and the carcinogenicity of P70(H) and P100(H) white mineral oils in Fischer-344 rats (F-344). The studies were identical in design and followed the Organization for Economic Cooperation and Development, Guidelines for Testing Chemicals, Guideline 453, 1981. Additional endpoints evaluated were: (1) extent of mineral hydrocarbon deposition in liver, kidneys, mesenteric lymph nodes, and spleen of female rats at 3, 6, 12, 18 and 24 months, and (2) reversibility of effects following cessation of exposure. Dietary concentration were 60, 120, 240, and 1,200 mg/kg/day, adjusted periodically to account for bodyweight changes. Study results were consistent with preceding subchronic studies. No treatment-related mortality, neoplastic lesions, or changes in clinical health, hematology, serum chemistry, or urine chemistry were evident in any group administered either white oil. Statistically significant higher food consumption was noted in the 1,200 mg/kg group males and females exposed to either white oil and statistically significant higher body weights were noted in the 1,200-mg/kg males during the latter portion of the P100(H) study. Higher mesenteric lymph node weights were accompanied by increased severity of infiltrating histiocytes. This occurred to a greater extent with the P70(H) than the P100(H) oil. No other histopathology of significance was observed. Mineral hydrocarbons were detected in the liver following exposure to either oil. Maximal concentrations of mineral hydrocarbons in the liver were similar with both oils but occurred more rapidly with the P70(H) oil. Liver mineral hydrocarbon content returned to near-background levels during the reversibility phase. In conclusion, lifetime exposer of F344 rats to P70(H) and P100(H) white oils resulted in only minimal findings and with no consequence to clinical health. Thus, under the conditions of these studies, the No Observable Adverse Effect Level (NOAEL) for these studies was considered to be 1,200 mg/kg/day.

Scientific Opinion on Mineral Oil Hydrocarbons in Food

“…The most common tumour types were mononuclear leukemia and pituitary/pars distalis adenoma (tumour incidences reported in Table 18). Table 18: Tumour incidences in rats exposed to P70(H) and P100(H) (Trimmer et al, 2004 The incidences of mononuclear leukemia in female rats at 240 mg/kg P70(H) and of pituitary/pars distalis adenoma in high dose females (1200 mg/kg) receiving P100(H) were within the respective historical control ranges for the strain of rat used and are considered incidental, and not treatment related.…”

“…In the liver, however, the microgranulomas were surrounded by inflammatory cells. Evidence from a two year carcinogenicity study on two high viscosity mixtures (P70(H) and P100(H)) suggest that the microgranulomas in liver and MLN do not cause a prolonged inflammatory response or other severe pathological changes following chronic exposure in Fischer rats (Trimmer et al, 2004). However, the CONTAM Panel concluded that it would be prudent to assume that liver microgranulomas, observed in the Fischer 344 rats, could be potentially relevant to humans and therefore the critical effect for the risk assessment of MOSH.…”

“…Preferential accumulation occurred in the alkane range approximately C 20 -C 35 . Trimmer et al (2004) investigated the MOSH deposition in liver, kidneys, mesenteric lymph nodes and spleen of female Fischer 344 rats dietary exposed to P70(H) and P100(H) white oils incorporated into the diet at concentrations to produce dose levels of 60, 120, 240 and 1 200 mg/kg b.w. per day, for up to two years.…”

“…Groups of 50 Fischer 344 (CDF® (Fischer 344)/CrlBR rats per sex group were administered white mineral oil in their diet for two years (Trimmer et al, 2004). The test mineral oils used met the United States Pharmacopoeia (USP) and Food and Drug Administration (FDA) criteria for food and food contact uses.…”

Scientific Opinion on the re‐evaluation of microcrystalline wax (E 905) as a food additive

“…Trimmer et al (2004) assessed long-term toxicity and carcinogenicity of two mineral oils: a medium viscosity mineral oil (kinematic medium 8.97 mm²/s at 100 °C) and a high viscosity mineral oil (kinematic viscosity 11 mm²/s at 100 °C) in a 2-year study, conducted in male and female F344 rats.…”