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Description of key information

Short description of key information on bioaccumulation potential result: 
See toxicokinetik, metabolism and distribution.
Short description of key information on absorption rate:
Under dermal in vitro test conditions, n-heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to n-heptane simultaneously reduced skin barrier function. Similar properties are expected for iso-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, 1982).

Key value for chemical safety assessment

Additional information

Differences in biological fate of inhaled nephrotoxic iso-octane and non-nephrotoxic n-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 n-octane was greater than iso-octane uptake at both concentrations. The uptake rates were 3.4 and 2.2 nmol/kg/min/ppm for low and high iso-octane levels, respectively. The fraction of inhaled hydrocarbon that was metabolised [sum of excreta, exhaled CO2 and carbon-14 equivalents in the carcass] was higher at low inhaled concentrations than at high inhaled concentrations.The major route of elimination was urine, for low exposure concentration14C in urine exceeded 11% of total inhaled iso-octane.The amount of inhaled 14C in the carcass at 70 hours post-exposure was less than 2% of total inhaled for both low and high concentrations. The fraction of inhaled parent compound exhaled unchanged was approx. 2%. Half of iso-octane 14C retained at the end of the 2 hour exposure was eliminated within 15 hours post-exposure but elimination continued primarily by the urinary route throughout 70 hours of observation.The almost exclusive elimination of metabolites of inhaled iso-octane via the kidney with little production of 14CO2 suggests that kidneys may be exposed to a higher concentration of potentially toxic high molecular weight metabolites of iso-octane.

In general, C7-C9alkanes 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.

Discussion on bioaccumulation potential result:

See toxicokinetik, metabolism and distribution.

Discussion on absorption rate:

There are no dermal absorption data available on iso-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 n-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 n-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 n-heptane had a damage ratio of 0.57, confirming that approx. 43% of the skin barrier function was lost due to exposure to n-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 n-heptane in the skin (0.01%) was less than the portion in the receptor solution (0.12%). The portion of n-heptane in the donor solution (wash) was 95.4%. In contrast to the Kp experiment, the skin (0.14%) retained a larger percentage of n-heptane following a 10 min exposure. The portion of n-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 n-heptane in the receptor solution (0.12%) than in the skin (0.06%). The increased proportion of n-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, n-heptane was able to penetrate the skin. During prolonged exposure, the penetration of the skin was aggravated, since the exposure to n-heptane simultaneously reduced skin barrier function.