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Endpoint summary

Additional information

Hydrocarbons are absorbed through the lung and the gastro-intestinal tract. They are widely distributed and excreted in urine or in exhaled air, depending on volatility. They are metabolised by ω- or ω-1 oxidation to the alcohol, and thence to the fatty acid. Fatty acids derived from hydrocarbons are likely to enter intermediary metabolism (including β–oxidation) and to be excreted in bile, in urine or in exhaled air (as carbon dioxide) [Illing, 2006]. Based on the octanol-water partition coefficient values for the constituents, 100% dermal absorption is assumed. The toxicokinetics of Fischer-Tropsch derived hydrocarbons is expected to be very similar to the toxicokinetics of petroleum-derived material of similar chain lengths and structures. Studies of hydrocarbon species in foodstuffs, plants and insects reveal that hydrocarbons with higher carbon numbers (generally up till about C40 but occasionally up to C60) are present. However, detailed reviews of mammalian tissues indicate that the hydrocarbon species present have generally carbon numbers less than C30, suggesting that hydrocarbons with higher carbon number ranges are not or are significantly less efficiently absorbed (Lester, 1979). Experimentally, the absorption of a wide range of hydrocarbons, including individual linear, branched and cyclic paraffins, was investigated in the male C-D rat following oral administration of simple mixtures of equal amounts of 3 or 4 different hydrocarbons at various doses, ranging from 50 to 530 mg/kg bw (Albro and Fishbein, 1970). The absorption of hydrocarbons was found to be inversely proportional to the carbon number according to the following equation (correlation coefficient 0.995; p<0.001): Percentage retained = 115.9 – (3.94 x number of carbon atoms). There was no statistically significant difference in the percentage absorbed for different isomers (branched or cyclic) compared to their n-aliphatic isomers (p >0.9). An almost constant percentage was absorbed between 60 and 320 mg/kg bw but at higher doses (up to 530 mg/kg bw) a gradual decrease to 70% of the maximum was observed (Albro and Fishbein, 1970). This experimentally determined equation predicts that hydrocarbons with carbon numbers greater than 30 are not absorbed to a significant extent. Furthermore, the validity of the equation has been confirmed for a number of hydrocarbons in different studies. For instance, squalane (2,6,10,15,19,23-hexamethyltetracosane, C30H62) is experimentally used as a marker for balance studies since it is not absorbed to a significant extent (Morgan and Hoffman, 1970; Low et al., 1992) while the radiolabelled marker 1-[14C]-1-eicosanyl-cyclohexane was absorbed for 11% in a study on the pharmacokinetics of white oils, which is essentially equal to the predicted value of 13% (Halliday et al., 2002). A large number of (sub)chronic studies has been performed on a wide range of food-grade white oils and waxes. These substances consist of linear, branched and cyclic hydrocarbons with carbon numbers ranging from C14 to C80. In one of these studies, F344 rats, a rat strain known to be most sensitive to accumulation of hydrocarbons, were fed 5 white oils and waxes at a level of 2% in the feed for 28 and 90 days. Chemical characterisation of the absorbed material revealed that hydrocarbons are selectively absorbed between C20 to C35 (Scotterer et al., 2003; Freeman et al., 1993). A summary of the available data on 12 white oils and waxes clearly shows that uptake was inversely related to molecular weight and viscosity but not oil type or processing. It was also clearly shown that substances with hydrocarbon chain lengths C20 to C30 were absorbed to a significant extent whereas substances with hydrocarbon chain lengths C35 to C70 had no significant absorption (Freeman et al., 1993). In conclusion, toxicokinetic studies with various complex mixtures of linear, branched and cyclic petroleum-derived hydrocarbons show that absorption is inversely correlated with carbon chain length and independent of isomeric form, preparation process or type of product. Constituents with carbon chain lengths up to C30-C35 are absorbed via the gastro-intestinal tract at 2-20% of the amount dosed. However, when present in a mineral oil, hydrocarbons of higher molecular weight, corresponding to chain lengths greater than C32-C35 are not absorbed to any significant extent (Boogaard, 2007).

References

Illing 2006, [unpublished report] Naphtha (Fischer-Tropsch), light, C4-C10 – branched and linear: Summary of toxicological information relevant to Annex VIIa notification endpoints, 2006.

Lester, 1979. Normal paraffins in living matter – occurrence, metabolism and pathology, Prog Food Nutr Sci 3(1-2): 1-66, 1979.

Albro and Fishbein, 1970. Absorption of aliphatic hydrocarbons by rats. Biochim Biophys Acta 219(2):437-46, 1970.

Morgan, RG, and Hoffman, AF, Use of 3H-labeled triether, a nonabsorbable oil-phase marker, to estimate fat absorption in rats with cholestyramine-induced steatorrhea, J Lipid Res 11(3): 231-6, 1970.

Low, KL, Shymanski, PM, Kommineni, C, Naro, PA, Mackerer, CR, 1992. Oral absorption and pharmacokinetic studies of radiolabelled normal paraffinic, isoparaffinic and cycloparaffinic surrogates in white oil in Fischer 344 rats, Toxicology Forum, Special meeting on mineral hydrocarbons, Green College, Oxford UK, Sep 21-23, 1992.

Halliday, JS, Mackerer, CR, Twerdok, LE and Sipes IG, 2002. Comparative pharmacokinetic and disposition studies of [1-[14C} =1-eicosanylcyclohexane, a surrogate mineral hydrocarbon, in female Fischer-344 and Sprague-Dawley rats, Drug Metab Dispos 30(12): 1470-7, 2002.

Scotterer, MJ, Castle, L, Massey, RC, Brantom, PF and Cunninghame, ME, 2003. A study of the toxicity of five mineral hydrocarbon waxes and oils in the F344 rat, with histological examination and tissue-specific chemical characterisation of accumulated hydrocarbon material, Food Chem Toxicol, 41(4): 489-521, 2003.

Freeman, J, Simpson, BJ, Tietze, P, (1993). White oil and waxes – summary of 90-day studies, CONCAWE Report 93/56, CONCAWE, Brussels, 1993

Boogaard, P, 2007. Toxicokinetic assessment of gastrointestinal absorption of hydrocarbons with carbon number greater than 35 with specific relevance to Residues (Fischer-Tropsch), C40-70, branched and linear, Unpublished report, Shell Health, 22 November 2007.