Hydrocarbons, C16-C22, n-alkanes, isoalkanes, <2% aromatics

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).

Dermal absorption of C10-C12 is low with permeability coefficients inversely proportional to carbon number (Kim, 2006). This conclusion is supported by a study showing that 95-98% of topically applied n-hexadecane did not penetrate fresh intact porcine skin regardless of vehicle utililised (Brown, 1994).

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 substances containing 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. Adsorption via the skin of >C16 is negligible. Single 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). Thus, hydrocarbons in a complex mix are less bioavailable than as single constituents.