Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics

Endpoint summary

Additional information

There are no toxicokinetic data available on hydrocarbons, C7-C9, n-alkanes, iso-alkanes, cyclics. However, there are reliable data available for other category members. Thus, read-across was conducted based on a category-approach.

The inhaled uptake of normal-heptane vapors was explored by Dahl et al. (1988) in male rats exposed for 5 consecutive days, 80 min/day with escalation of vapor concentration daily (from 1 ppm up to 5000 ppm). During the exposures, respiratory and gas chromatographic data were collected at 1 min intervals. For normal-heptane, only data from one exposure at 100 ppm were available. Uptake of inhaled normal-heptane vapor was 4.5 ± 0.3 nmol/kg/min/ppm (n = 10). The value is given for uptake during minutes 60 to 70 from the start of exposure of the experiment. Taking into account all data of the report, a number of trends relating uptake to chemicals properties were observed. Among these, highly volatile hydrocarbons are less well-absorbed than less volatile hydrocarbons; unsaturated compounds are better absorbed than saturated ones; and branched hydrocarbons are less well-absorbed than unbranched ones. These trends can be used to predict relative uptake rates within classes of hydrocarbons.

In a subsequent study, differences in biological fate of inhaled nephrotoxic iso-octane and non-nephrotoxic n-octane were explored by Dahl (1989) in rats exposed to 14C-labeled vapor by nose-only inhalation at concentrations of 0, 1.0, and 350 ppm for a single 2 hour exposure. Radioactivity of exhalant, urine, and feces was measured for 70 hours post-exposure after which residual radioactivity in the carcasses was determined. Inhaled uptake of n-octane was greater than iso-octane uptake at both concentrations. The uptake rate at the low concentration for n-octane was twice that of the high concentration (6.1 and 3.4 nmol/kg/min/ppm, respectively).

The major route of elimination of 14C was carbon dioxide. For n-octane absorbed at low concentration, the amount of inhaled 14C in the carcass at 70 hours post-exposure was nearly 5% of total inhaled, a significantly higher level than that remaining after high concentration exposure (approx. 2%). The fraction of inhaled n-octane exhaled unchanged was 4.5 and 6.5% of high and low exposure levels, respectively. Half of n-octane 14C retained at the end of the 2 hour exposure was eliminated within 5-10 hours post-exposure and stopped after 30 hours when 75-85% of activity was eliminated. The rate of excretion of n-octane was markedly affected by the concentration of inhaled vapor. The ratio of 14CO2 to 14C in urine was 5:1 after inhalation at the low concentration but 1:1 after inhalation at the high concentration.

The excretion pattern of n-octane, fairly evenly distributed between 14CO2 and kidney by 15 hours, and the rapid elimination differed from that of iso-octane for which excretion was primarily through the kidney at a slower rate.

Toxicokinetic properties of normal-heptane were investigated in rats during inhalation of 100 ppm of the hydrocarbon for 3 days, 12 hours/day (Zahlsen et al., 1992). The concentration of normal-heptane was measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat. Normal-heptane was found in moderate concentrations in the kidneys and only in marginal concentrations in blood, brain and liver. In perirenal fat, concentrations were the highest, however, decreasing with lasting exposure. This is in contrast to other n-alkanes, which showed increasing concentrations.

Partition coefficients of normal-heptane were determined in human blood and tissues by Perbellini et al. (1985). The solubility of n-heptane was tested in blood, saline, olive oil and in the most important human tissues (lung, kidney, liver, brain, muscle, heart, and fat). The solubility of normal-heptane in saline was low and very high in olive oil, displaying a partition coefficient of 452 (20.0 SD). The partition coefficients were therefore high in fat and fatty tissues compared to the other examined tissues.

Based on read-across from structurally related substances within a category approach, C7-C9 alkanes are readily absorbed and distributed through the body. n-Alkanes are readily metabolized and excreted in urine and expired as CO2. iso-alkanes are less readily metabolized to a range of metabolites that are excreted in the urine. Tissue/blood ratios are greater than unity, especially for iso-alkanes, but on prolonged administration, metabolizing enzymes appear to be induced and ratios decrease. For n-alkanes, there appears to be a very low rate of metabolism to potentially neurotoxic gamma diketones, and no such metabolism for the iso-alkanes.