Toxicometabolomics: Identification of markers of chronic exposure to low doses of aliphatic hydrocarbons

The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalation exposure to low doses of aliphatic hydrocarbons (HC) with the number of carbon atoms from 6 to 10. The metabolic profile was determined by a combination of gas chromatography/mass spectrometry and high-performance liquid chromatography/high-resolution mass spectrometry with the subsequent use of chemometrical methods for data treatment and presentation. It was shown that continuous 90-day exposure to a mixture of C-6-C-10 saturated hydrocarbons at a concentration of 160 +/- 20.5 mg/m(3) leads to various metabolic impairments in the liver and kidneys. Exposure to hydrocarbon mixtures at doses of 31.4 +/- 5.6 and 5.2 +/- 1.8 mg/m(3) evoked significantly smaller changes. Novel metabolic markers of the toxic effect of low concentrations of C6-C10 aliphatic hydrocarbons were revealed. The concentration ratio of pyrophosphoric and oxalic acids in rat blood plasma was found to be the most sensitive marker called a pyrophosphate index. A hypothesis was proposed about the disturbance of the redox balance as a leading pathogenetic mechanism of neuropathies and concomitant pathologies associated with chronic HC intoxication.