Metabolism

White spirit is a complex mixture of aliphatic and aromatic hydrocarbons and information on its metabolism is limited. Metabolic pathways have been elucidated for only a small portion of the numerous chemicals in white spirit (Rothman and Emmet, 1988). It is impossible to extrapolate from these findings when attempting to predict the metabolic reactions of a mixture. The simultaneous metabolism of the different chemicals in the white spirit mixture introduces additional factors which will influence kinetics, e.g., inhibition or induction of the metabolising enzyme systems.

The aliphatic hydrocarbons primarily undergo oxidative conversion to alcohols catalysed by cytochrome P450 dependent monooxygenases in the liver. For n-alkanes with a carbon chain of 7 or less, oxidation to alcohol predominantly occurs at the penultimate carbon (ra-1 oxidation) giving secondary mono- or dialcohols. In higher alkanes, only oxidation at the terminal carbon has been observed (ra-oxidation), and branched alkanes are oxidised at either the ra or ra-1 position, resulting in secondary or tertiary alcohols. Monocyclic and polycyclic alkanes are oxidised at the CH2-group in the ring structure. After these primary conversions, phase II conversion occurs with conjugation of the hydroxy groups to form excretable glucuronide or sulphatide conjugates (Bondy, 1995; IPCS, 1996).

Alkyl benzenes are mainly oxidised to alcohols via the cytochrome P450 enzyme system. Alternatively, direct hydroxylation of the aromatic structure can occur and the resultant hydroxy groups are either conjugated to glucuronic acid or sulphate, or further oxidised to ketone/aldehyde or carboxylic acid, and then conjugated to glucuronic acid, sulphate or glycine (IPCS, 1996).

The polyaromatic hydrocarbons (e.g., benzene, naphthalene) are oxidised by cytochrome P450 to form arene oxides. With further oxidation and hydration, the ring structure may break and in the case of benzene this results in the formation of very reactive benzoquinones (IPCS, 1996).

The aromatic component of white spirit contains a small percentage of trimethylbenzene isomers (1%), which are oxidised to dimethylbenzoic acid isomers (Pfäffli et al., 1985), and these have been used as markers for exposure to white spirit (Verkkala et al., 1984; Pfäffli et al., 1985; Järnberg et al., 1998).

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