Accumulation and Distribution of Aliphatic (n‐Nonane), Aromatic (1,2,4‐Trimethylbenzene) and Naphthenic (1,2,4‐Trimethylcyclohexane) Hydrocarbons in the Rat after Repeated Inhalation

Abstract

The concentrations of the C9 hydrocarbons n-nonane, 1,2,4-trimethylbenzene and 1,2,4-trimethylcyclohexane were measured in rat blood, brain and perirenal fat after exposures to 1000 p.p.m. of the individual compounds. Measurements were made by head space gas chromatography at the end of 12 hr exposures on days 1, 3, 7, 10 and 14 of the exposure periods. The relative concentrations of hydrocarbons in each organ were, brain: n-nonane "trimethylcyclohexane approximately trimethylbenzene, blood: trimethylbenzene "n-C9 greater than trimethylcyclohexane and perirenal fat: trimethylbenzene greater than n-nonane greater than trimethylcyclohexane, showing the widely different distribution properties of the different hydrocarbons. Brain/blood ratios of 11.4, 2.0 and 11.4, and fat/blood ratios of 113, 63 and 135 were found for n-nonane, trimethylbenzene and trimethylcyclohexane, respectively. A marked decrease in biological concentrations of trimethylbenzene and trimethylcyclohexane during the initial phase of exposure indicate that these hydrocarbons are capable of inducing their own metabolic conversion resulting in lower steady state levels. A special attention was made to n-nonane showing the highest concentration in brain concomitantly with a low blood concentration. This observation demonstrate that biological monitoring of occupational exposure by blood measurements not should be performed without knowledge of the distribution properties of the compounds investigated.

Toxicokinetics of Inhaled Trimethylbenzenes in Man

“…Rat tissue/blood partition coefficients in vivo can be calculated from measured concentrations in different organs after exposure to TMB. The rat fat/blood partition coefficient of 1,2,4-TMB in vivo has been determined to be 63 (92). This value is about half that indicated in the present study.…”

Characterization of the toxicological hazards of hydrocarbon solvents

“…Levels of aromatics in blood and fat were higher than those of the corresponding aliphatics at both low and high exposure levels, but levels of aromatics in the CNS were similar to those of n-paraffins and lower than those of cycloparaffins (Eide and Zahlsen 1996). In other studies, however, systemic absorption of n-alkanes appeared to be lower than levels of cycloparaffins over the C6-C9 carbon number range, but higher for C10 alkanes than for the corresponding cycloparaffins (Zahlsen et al 1992(Zahlsen et al , 1993.Compared to aromatics, similar brain/blood, fat/blood and fat/brain ratios for n-nonane and 1,2,4-trimethylcyclohexane indicated strong similarities in biological affinities to proteins and/or lipids, solubility, and tissue distribution at high exposure concentrations (500-1000 ppm) (Zahlsen et al 1990). In a study to evaluate tissue distribution of C6-C10 n-paraffins, aromatics and cycloparaffins, rats were exposed 12 hours/day for 3 consecutive days to each of these constituents at 100 ppm.…”

“…Compared to aromatics, similar brain/blood, fat/blood and fat/brain ratios for n-nonane and 1,2,4-trimethylcyclohexane indicated strong similarities in biological affinities to proteins and/or lipids, solubility, and tissue distribution at high exposure concentrations (500-1000 ppm) (Zahlsen et al 1990). In a study to evaluate tissue distribution of C6-C10 n-paraffins, aromatics and cycloparaffins, rats were exposed 12 hours/day for 3 consecutive days to each of these constituents at 100 ppm.…”

“…It should be noted that the aromatic hydrocarbons can induce their own metabolism (Zahlsen et al 1990(Zahlsen et al , 1992, therefore in experimental studies, the rates of elimination of aromatic constituents increase with increasing dose and time of treatment Hydrocarbon solvent toxicology 289 DOI 10.3109/10408444.2015.1016216 (McKee et al 2010. The aliphatic constituents do not appear to induce their own metabolism, but if metabolism is induced by co-exposure to aromatics, the rates of elimination of the aliphatic constituents are also increased (Jarnberg et al 1997).…”

“…That this is true is demonstrated empirically by evidence that the results of studies of complex solvents, summarized in the appendices, are similar to those of mono-constituents or solvents with narrowly restricted carbon number ranges or are comprised of specific hydrocarbon types. The characteristics that have the greatest influence on the differing properties of hydrocarbon solvents are those related to physical/chemical properties.It should be noted that the aromatic hydrocarbons can induce their own metabolism (Zahlsen et al 1990(Zahlsen et al , 1992, therefore in experimental studies, the rates of elimination of aromatic constituents increase with increasing dose and time of treatment Hydrocarbon solvent toxicology 289 DOI 10.3109/10408444.2015.1016216 (McKee et al 2010. The aliphatic constituents do not appear to induce their own metabolism, but if metabolism is induced by co-exposure to aromatics, the rates of elimination of the aliphatic constituents are also increased (Jarnberg et al 1997).…”