Bioaccumulation and toxicity of mineral oil hydrocarbons in rats ‐ specificity of different subclasses of a broad mixture relevant for human dietary exposures

Abstract

The purpose of this study was to investigate the fate and effects of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats. Animals were fed control diet or diet containing various MOSH mixtures at concentrations ranging from 40 to 4000 mg/kg feed for up to 120 days. MOSH were analysed in liver, spleen, adipose tissue and remaining carcass at different sampling times. In addition to clinical effects, liver microgranulomas, hepatic inflammation, and disruption of the immune function were the main toxicological endpoints investigated. Arthritis symptoms were specifically studied in dark agouti rats. The results indicate that accumulation of MOSH depends on the mixture tested but always occurred predominantly in the liver and to a lesser extent in adipose tissue and spleen. Strong differences exist between liver and adipose tissue in terms of accumulated hydrocarbons: whereas in adipose tissue the accumulated fraction corresponds to the most volatile part of the administered mixture, in the liver, the most volatile as well as the highest boiling part of the mixture are almost absent. Also the types of hydrocarbons differ. When exposure ceases, a significant decrease of MOSH concentration was observed in the liver, but not in adipose tissue. MOSH exposure results in a significant increase in absolute and relative liver weights, the effect being dose-related, but also dependent on the mixture tested. There were large differences in the ability of the different mixtures to induce liver granulomas. The highest incidence was observed with the mixture containing the highest proportion of n-alkanes, suggesting that this fraction could play a significant role in the development of hepatic granulomas. No effects were found on the immune function, irrespective of the mixture or the dose tested.

Mineral oil in food, cosmetic products, and in products regulated by other legislations

“…In female F-344 rats, the strong retention in liver following exposure to paraffin waxes (e.g. LMPW) indicates the inability to efficiently metabolize absorbed n-alkanes consisting of a certain carbon number range (Smith et al 1996;Griffis et al 2010; Barp et al 2017b;Cravedi et al 2017). Even very low concentrations (0.02-0.12 ppm) of natural n-alkanes in the range of C 29 -C 33 , that were present in control feed, were found to be enriched in liver of untreated control animals (Cravedi et al 2017).…”

“…Paraffinum liquidum), L-C25W: a 1:1 (w/w) mixture of L-C25 and a paraffin wax (W) (see Table 1). would be an additional factor contributing to the slow biotransformation (Barp et al 2017b;Cravedi et al 2017).…”

“…Depicted granuloma densities represent the medians of the treatment groups; individual density values ranged up to $800 granulomas per cm 2 . Data were compiled from Baldwin et al (1992), Firriolo et al (1995), Smith et al (1995Smith et al ( , 1996, Scotter et al (2003), Griffis et al (2010), McKee et al (2012), and Cravedi et al (2017). For the nomenclature of mineral oils and waxes, see legend of Figure 6.…”

“…methylated) derivatives. Adapted from Miller et al (1996), EFSA (2012), McKee et al (2012), Barp et al (2017b) and Cravedi et al (2017). Mineral-oil type abbreviation: N: naphthenic (crude oil source); P: paraffinic; H: hydro-treated (catalytic hydrogenation); A: acid-treated; number (15, 70, 100): approximate viscosity (mm 2 /s) at 40 C.…”

Re‐evaluation of name of hydrogenated poly‐1‐decene (E 907) as food additive

“…mass spectrometry). However, FID is not selective, a drawback in view of the broad patterns of unresolved peaks of unidentified components formed by mineral oils (Biedermann et al, 2009;Cravedi et al, 2017) reported Grob (2018), on-line coupled high-performance liquid chromatography (HPLC) and GC-FID) (HPLC-GC-FID)) appears to be the method of choice and its successful application was reported already in 1984 (Grob et al, 1984). The aforesaid methodology makes use of solvent effects and retention gap technology: raw food extracts or solutions of edible oils could be directly injected, which not only provided a high-performance pre-separation, but also avoided contamination during sample preparation with virtually ubiquitous mineral oil hydrocarbons.…”