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Description of key information

Absorption: Expected to occur via oral and inhalation routes. Dermal absorption is low. However, read-across data after repeated dermal exposure is used for hazard assessment, since the dermal route is considered the most relevant route of human exposure in repeated toxicity study and in carcinogenicity study (Agency for Toxic Substances and Disease Registry, 1995 and Biles, R.W., et al., 1988).
Distribution: Expected to distribute mainly to fat tissue.
Metabolism: Based on the available data aliphatic hydrocarbons and aromatic hydrocarbons are oxidised to various alcohol and carboxylic acid derivatives.
Excretion: Based on the available data aliphatic and aromatic hydrocarbons and their metabolites are rapidly excreted, either exhaled from the lungs or excreted in the urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

There are no experimental studies of the toxicokinetic of renewable hydrocarbons of wood origin (diesel type fraction), but there are several studies available of the substance constituents. The first part of the discussion on toxicokinetics is based on physical and chemical properties of the substance. The second part concentrates on toxicokinetics of major constituents of the substance.

Absorption

Based on physicochemical considerations uptake of substances across the gastrointestinal tract may occur when the log Pow is greater than 4 and water solubility is equal to or less than 1 mg/l. In addition, direct uptake of substances across the respiratory epithelium by passive diffusion is favoured when the log Pow is greater than 4 and water solubility is equal to or less than 1 mg/l. On the other hand, dermal uptake of substances with a log Pow of 6 or above and water solubility less than 1mg/ml will be low.

The experimentally determined log Pow for renewable hydrocarbons of wood origin (diesel type fraction) is 6 and its experimentally determined water solubility is 1.0 mg/l. However, since this substance is a complex mixture of hydrocarbons, the testing of the above properties is not technically feasible as the methods are intended to single substances. The physicochemical and toxicological properties are also dependent on the properties of the hydrocarbon blocks in the substance. Therefore, the estimated log Pow and water solubility of the representative hydrocarbon blocks were taken into account for assessment of toxicokinetics of the substance.

Log Kow values were also estimated with the PETRORISK tool that was used for the environmental risk assessment. The estimation is based on log Kow values of individual compound structures, which are included in the CONCAWE Library. The overall range for the estimated log Kow values was from 2.55 to 13.23. The log Kow values of the representative individual structures that form the major part of the substance based on mass fraction (sum 0.64) were in the range 5.25 - 9.82.

In addition to PETRORISK, the octanol-water partition coefficients were estimated with the EPISUITE model. The calculated log Kow values for the ten most abundant individual structures (based on mass-%) of the substance ranged from 7.71 to 10.16.

The water solubility was also estimated with the PETRORISK tool that was used for the environmental risk assessment. The estimation is based on water solubility values of individual compound structures, which are included in the CONCAWE Library. The overall range for the estimated water solubility values was from 0.000000001 mg/L to 510 mg/L. The water solubility values of the representative individual structures that form the major part of the substance based on mass fraction (sum 0.64) were in the range 0.0000037 mg/L - 0.37 mg/L.

As conclusion based on the experimental and estimated water solubility values and the octanol-water partition coefficients the uptake of renewable hydrocarbons of wood origin (diesel type fraction) from the gastrointestinal tract and by lung may occur. Instead, the uptake by the skin is expected to be low.

Distribution

Based on physicochemical considerations, the molecule is highly lipophilic, if log P > 4 and it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues.

Renewable hydrocarbons of wood origin (diesel type fraction) is a lipophilic substance (log Pow = 6) with limited water solubility (1 mg/L). Based on this data the substance is likely to distribute into cells, especially in adipose tissue.

Metabolism

There is no experimental data available on the fuel oils to estimate the route of metabolism and possible metabolites. It is very difficult to predict the metabolic changes a substance may undergo only on the basis of physico-chemical information, because this substance is a complex mixture of hydrocarbons with different physico-chemical properties.

Excretion

There is no quantitative information on the excretion of surrogate substances, such as fossil diesel fuels, following inhalation, oral, or dermal exposure in humans or animals.

This renewable diesel fuel is composed mainly of C9-C24 non-aromatic hydrocarbons (ca. 82 % w/w) and of C9-C23 aromatic hydrocarbons (ca. 5.5 % w/w). Absorption, distribution, metabolism and excretion of these compounds are discussed below. This summary is based on the OECD existing Chemicals database (OECD, 2013)

Absorption

It is estimated that approx. 50 % of a C14-C20 hydrocarbon solvent and approx. 70 % of a C9-C14 hydrocarbon solvent would be absorbed when ingested. When inhaled, especially short chain hydrocarbons are readily absorbed. Based on the data from a human volunteer study, percutaneous absorption of C9-C14 aliphatic constituents would be in the range of 0.01 %/hr to 0.1 %/hr and that of aromatic constituents would be approximately 0.2 %/hr. There is also available an in vitro dermal study of C16 hydrocarbon, hexadecane (CAS 544-76-3). Dermal absorption of hexadecane was determined to be only 0.18 % of the applied dose. Based on these data other constituents of the substance are expected to have similarly low dermal absorption rates.

Distribution

C9 -C14 aliphatic hydrocarbons are widely distributed throughout the body of both humans and animals and preferentially accumulate in the adipose tissues due to the lipophilic nature of the solvents. A toxicokinetic study on the distributions of C9 to C10 alkanes, aromatics and cycloalkanes in blood, brain, liver, kidney and perirenal fat demonstrated that aromatics generally showed higher blood concentrations than alkanes and cycloalkanes. C9 cycloalkanes showed higher brain concentrations than the corresponding aromatics and alkanes, while brain concentrations of C10 alkanes were slightly greater than C10 cycloalkane concentrations, which in turn were greater than C10 aromatic concentrations. Fat contained the highest concentrations of each of the hydrocarbons examined; concentrations of aromatics and cycloalkanes in fat were higher than concentrations of alkanes.

Metabolism

Aliphatic hydrocarbons are typically metabolized by side chain oxidation to alcohol and carboxylic acid derivatives by cytochrome P-450 dependent monooxygenases. These metabolites can be glucuronidated and excreted in the urine or further metabolized before being excreted. C10 -C13 aromatic hydrocarbons are typically metabolized by side chain oxidation to alcohol and carboxylic acid derivatives. In guinea pigs dosed orally, the methylnaphthalenes are preferentially metabolized by side chain oxidation to form naphthoic acids, although ring oxidation can also occur. These metabolites can be glucuronidated or further metabolized before being excreted.

Excretion

Generally speaking, it is expected that components or metabolites of C9-C14 hydrocarbons that have low solubility in the blood, would be rapidly exhaled from the lungs. The metabolites of longer chain aliphatics (C14-C20) and C10-C13 aromatics are expected to be excreted in the urine and to a lower extent, in the feces. Excretion is expected to be rapid with the majority of the elimination occurring within the first 24 hours of exposure.