Mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats; accumulation of wax components; implications for risk assessment

• Published in: The Science of the total environment 2017-04, Vol.583, p.319-333
• Main Authors: Barp, Laura, Biedermann, Maurus, Grob, Koni, Blas-Y-Estrada, Florence, Nygaard, Unni C, Alexander, Jan, Cravedi, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Animals; Class I mineral oils; Crystallization of waxes; Female; Granulomas; Hydrocarbons - toxicity; Life Sciences; Liver - metabolism; Mineral Oil - toxicity; Mineral waxes; n-Alkanes; Naphthenes; Rats; Rats, Inbred F344; Risk Assessment; Spleen - metabolism; Toxicity Tests
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2017.01.071

Female Fischer 344 rats were exposed to three MOSH mixtures: oils largely below and above C25 (S-C25 and L-C25) and a 1:1 mixture of L-C25 with a wax; doses of 400, 1000 and 4000mg/kg feed were administered during 120days. MOSH were determined by on-line HPLC-GC-FID in liver, spleen, adipose tissue and the carcass. The composition of the hydrocarbons accumulated in the tissues was further analyzed by comprehensive two-dimensional GC (GC×GC). MOSH in the mass range of C26–30 were more strongly accumulated than those between C20–25, which does not support the present classification of MOSH differentiating at n-C25 for risk assessment. Compared to the total of the MOSH, n-alkanes and n-alkyl monocyclic naphthenes were generally enriched in adipose tissue. In liver and spleen, n-alkanes up to C25 were eliminated, but strongly accumulated at around C30. Based on this profile, poor solubility and the melting points, it is hypothesized that crystallization protects these wax components against metabolism and elimination. In the liver, relative retention of n-alkanes decreased again beyond C30, accentuated at high exposure, suggesting reduced absorption. Compared to the animal data, accumulation of n-alkanes from food sources, such as apples, into human tissues seems low, perhaps because of low absorption due to their presence in crystalline form. A series of dominant isoalkanes, accumulated in all tissues analyzed, was characterized, though without proposing a structure. Implications on present regulation of white mineral oil products are discussed. Section of a GC×GC-FID plot showing that in rat liver the basically easily metabolized n-alkanes are indeed largely absent below n-C25, but strongly enriched compared to the other hydrocarbons above about n-C25 (spots above the dashed lines, some labeled by C-number). [Display omitted] •In liver and spleen, accumulation of the C26–30 MOSH is higher than that of C20–25.•n-Alkanes melting above about 55°C are accumulated in liver and spleen.•Wax crystallization: a reason for accumulation and initiating granuloma formation?•A series of dominant branched open chain alkanes resisted elimination.•Regulatory classification and reference values need revision.