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Description of key information

Short description of key information on bioaccumulation potential result: 
See toxicokinetics, metabolism and distribution.
Short description of key information on absorption rate:
Under dermal in vitro test conditions, normal-heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to normal-heptane simultaneously reduced skin barrier function. Similar properties are expected for octane.
Due to the experimental setup, e. g. undepletable reservoir of test substance and therefore absence of any evaporation, the dermal penetration factors reported by Fasano and McDougal (2008) are very conservative. In contrast, when using a diffusion cell, which is a more realistic setup for volatile subsances like hydrocarbon solvents, dermal penetration rates of 0.1 µg/cm2/h and 0.0005 µg/cm2/h were obtained for heptane and octane, respectively (Tsuruta et al., 1982).

Key value for chemical safety assessment

Additional information

The inhaled uptake of octane 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. Uptake of inhaled octane vapors (of 2 independent experiments, each n = 10) was 7.1 ± 1.0 nmol/kg/min/ppm and 6.1 ± 0.6 nmol/kg/min/ppm. The values are given for uptake during minutes 60 to 70 from the start of exposure of the experiment.

In a subsequent study, differences in biological fate of inhaled nephrotoxic iso-octane and non-nephrotoxic octane were explored by Dahl (1989) in rats exposed to14C-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 octane was greater than iso-octane uptake at both concentrations. The uptake rate at the low concentration for 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 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 octane exhaled unchanged was 4.5 and 6.5% of high and low exposure levels, respectively. Half of 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 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 octane, fairly evenly distributed between14CO2 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 octane 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 octane was measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat. Octane was found in higher concentrations in kidneys and in lower concentrations in blood and liver. The lowest tissue levels were determined on day 3. In perirenal fat, concentrations were the highest with concentrations increasing from day 1 to day 3.

 

In general, octane is readily absorbed and distributed through the body. Furthermore it is readily metabolized and excreted in urine and expired as CO2. Based on read-across from the structurally related compound normal-heptane within a category approach, there appears to be a very low rate of metabolism to potentially neurotoxic gamma diketones in rats.

Discussion on bioaccumulation potential result:

See toxicokinetics, metabolism and distribution.

Discussion on absorption rate:

There are no dermal absorption data available on octane. However, there are reliable data available for another category member. Thus, read-across was conducted based on a category-approach.

Fasano and McDougal (2008) described the procedures for determination of a permeability coefficient (Kp) and two short-term dermal absorption rates at 10 and 60 min. The flux values for normal-heptane and the 10 and 60 min short-term absorption values (the quantity of chemical remaining in the skin plus that portion that had penetrated the skin was detected in the receptor fluid) were 63.2 µg/cm2/h, 113 µg/cm2/h (for the 10 min flux) and 22.1 µg/cm2/h (for the 60 min flux). Therefore, the 10 min flux value for normal-heptane (based on both the amount in the skin and the receptor solution) was greater than the flux measured in a similar manner over 60 min.

Skin integrity measurements were taken before and after each experiment. A ratio of post- to pre-test impedance of "1" indicates that the skin barrier did not change over the course of the experiment. In the Kp experiments, skin exposed to normal-heptane had a damage ratio of 0.57, confirming that approx. 43% of the skin barrier function was lost due to exposure to normal-heptane. The barrier properties for the skin in the short-term experiments were given as the ratios of 0.90 for 10 min and 0.88 for 60 min. At the end of the Kp experiment, the portion of normal-heptane in the skin (0.01%) was less than the portion in the receptor solution (0.12%). The portion of normal-heptane in the donor solution (wash) was 95.4%. In contrast to the Kp experiment, the skin (0.14%) retained a larger percentage of normal-heptane following a 10 min exposure. The portion of normal-heptane in the donor solution (wash) was 6.84% at 10 min. The greater portion of the applied dose remaining in the skin at 10 min suggests that partitioning into the skin from the donor solution is the driver of penetration with this brief exposure. After the 60 min experiments, there was also a larger percentage of normal-heptane in the receptor solution (0.12%) than in the skin (0.06%). The increased proportion of normal-heptane detected in the receptor solution illustrates and confirms the movement of the chemical from the skin into the receptor solution. Under the test conditions, normal-heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to normal-heptane simultaneously reduced skin barrier function.