title: Accumulation of mineral oil saturated hydrocarbons (MOSH) in female Fischer 344 rats: Comparison with human data and consequences for risk assessment.
abstract: 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.
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Zurich, Fehrenstrasse 15, P.O. Box, CH-8032 Zurich, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Barp
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Zurich, Fehrenstrasse 15, P.O. Box, CH-8032 Zurich, Switzerland.
authors.forename: Maurus
authors.initials: M
authors.lastname: Biedermann
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Zurich, Fehrenstrasse 15, P.O. Box, CH-8032 Zurich, Switzerland. Electronic address: koni@grob.org.
authors.forename: Koni
authors.initials: K
authors.lastname: Grob
authors.affiliation: Toxalim, INRA, ENVT, INP-EIPurpan, Université de Toulouse, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Blas-Y-Estrada
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Unni C
authors.initials: UC
authors.lastname: Nygaard
authors.affiliation: Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, N-0403 Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Alexander
authors.affiliation: Toxalim, INRA, ENVT, INP-EIPurpan, Université de Toulouse, Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cravedi
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D006838:Hydrocarbons / Q000493:pharmacokinetics*; D008099:Liver / Q000737:chemistry*; D008899:Mineral Oil / Q000493:pharmacokinetics*; D010938:Plant Oils; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D013154:Spleen / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D006838:Hydrocarbons; D010938:Plant Oils; D008899:Mineral Oil
keywords: Alkyl monocyclic hydrocarbons; Bioaccumulation; Class I mineral oil; Comprehensive two-dimensional gas chromatography (GCxGC); Molecular mass distribution