Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats: Comparison with human data and consequences for risk assessment

• Published in: The Science of the total environment 2017-01, Vol.575, p.1263-1278
• 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: Alkyl monocyclic hydrocarbons; Animals; Bioaccumulation; Class I mineral oil; Comprehensive two-dimensional gas chromatography (GCxGC); Female; Humans; Hydrocarbons - pharmacokinetics; Life Sciences; Liver - chemistry; Mineral Oil - pharmacokinetics; Molecular mass distribution; Plant Oils; Rats; Rats, Inbred F344; Risk Assessment; Spleen - chemistry; Tissue Distribution
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2016.09.203

Female Fischer 344 rats were orally exposed to a mixture of mineral oil saturated hydrocarbons (MOSH) of broad molecular mass range at doses of 40, 400 and 4000mg/kg feed. Amounts and compositions of the MOSH were analyzed in liver, spleen, adipose tissue and the carcass after exposure during 30, 60, 90 and 120d as well as after 90d exposure followed by 30d depuration. At 40mg/kg in the feed, after 30d of exposure, 10.9% of the ingested MOSH were recovered from the animal body; after 90d plus 30d depuration it was 3.9%. In liver and spleen, the maximum retention in terms of molecular mass (simulated distillation) was at n-C29; in adipose tissue and carcass it was at n-C15/16. The differentiation between MOSH below and above n-C25 (Class I versus Class II and III oils), used for present regulation, is not supported by the present data on accumulation; structural characteristics seem more pertinent than molecular mass. Concentrations in the tissues increased far less than proportionally with the dose, rendering linear extrapolation to low doses questionable. No steady state was reached after 120d. In fact, comparing with the concentrations in human tissues at the estimated exposure, extrapolation from animal experiments seems to grossly underestimate human internal exposure. Comprehensive two-dimensional gas chromatography (GCxGC) was used to characterize the MOSH residues in the tissues with the aim of identifying the most strongly accumulated types. In the liver and spleen, the highly branched hydrocarbons dominated, whereas in the adipose tissue it was the n-alkanes and species with main n-alkyl moieties. Strong MOSH accumulation is not of concern per se, but the safety at the high concentrations in human tissues needs to be re-evaluated, possibly taking into account also end points other than granuloma formation. •MOSH concentrations in human tissues higher than extrapolated from animal experiments•Low accumulation at high exposure renders extrapolation to low doses questionable.•The maximum MOSH accumulation in liver and spleen is at C29.•Maximum accumulation of MOSH in the region of oils with high ADI•Branched alkylated naphthenes as dominant accumulated MOSH in liver and spleen The maximum accumulation of MOSH in the liver and spleen of rats is at alkanes C29, which is in the range of the Class I oils to which presently a high ADI is allocated. [Display omitted]