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Administrative data

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Description of key information

Short description of key information on bioaccumulation potential result: 
The percent retention of aliphatic hydrocarbons structurally similar to the registered substance following oral absorption was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% for C28 compound. Based on the empirical relationship, absorption of the registered substance is estimated to be ~33%. Metabolism data on aliphatic hydrocarbons supports that the registered substance undergoes metabolism via side chain oxidation followed by further oxidization to the corresponding fatty acids or conversion to glucuronide conjugates that would be excreted in the urine. Fatty acid metabolites can be degraded further via the beta-oxidation cycle or undergo conjugation to water-soluble products that are excreted in the urine. Unabsorbed parent alkane material from an orally administered dose would be expected to pass through the GI tract and eliminated, mainly unchanged, in the feces. The parent material is not sufficiently volatile for elimination to occur via the respiratory tract in expired air. As a result of the lack of systemic toxicity and the ability of the parent material to undergo metabolism and rapid excretion, bioaccumulation of the test substance in the tissues is not likely to occur.
Short description of key information on absorption rate:
The registered substance is minimally absorbed by the dermal route.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information

Assessment of the toxicokinetic behavior of the registered substance is based on data for structurally analogous substances. In a toxicokinetic study evaluating oral absorption of C14-C28 n-paraffins, retention was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% for C28 compound. Based on the empirical relationship, absorption of the registered substance is estimated to be ~33%. Metabolism data on aliphatic hydrocarbons supports that the registered substance undergoes metabolism via side chain oxidation followed by further oxidization to the corresponding fatty acids or conversion to glucuronide conjugates that would be excreted in the urine. Fatty acid metabolites can be degraded furtherviathe beta-oxidation cycle or undergo conjugation to water-soluble products that are excreted in the urine. Unabsorbed material from an orally administered dose would be expected to pass through the GI tract and eliminated, mainly unchanged, in the feces. The registered substance is not sufficiently volatile for elimination to occur via the respiratory tract in expired air. As a result of the lack of systemic toxicity and the ability of the parent material to undergo metabolism and rapid excretion, bioaccumulation of the test substance in the tissues is not likely to occur.

Discussion on bioaccumulation potential result:

Assessment of the toxicokinetic behavior of the registered substance is based on data for structurally analogous substances. The data support that the registered substance is not extensively absorbed from the gastrointestinal tract following oral administration and the predominant route of excretion is via the faeces. Following absorption, saturated alkanes such as the registered substance undergo metabolism to the corresponding hydroxylated and fatty acid metabolites, which in turn can be conjugated and excreted in the urine (major route of elimination). Any unabsorbed material would simply be excreted in the feces. 

The registered substance constitutes a relatively lipid-soluble, fully saturated hydrocarbon fluid, i. e., minimally branched paraffin material which falls in the chemical class of “saturated branched alkanes”. Its partition coefficient indicates that the material may pass across membranes.  However, there was no evidence of systemic toxicity in acute or repeated dose oral and dermal studies in rats exposed to structurally analogous materials. The lack of any signs of systemic toxicity in the acute or repeated oral and dermal dose studies provides suggestive evidence that absorptionviathe gastrointestinal tract or skin is low or very limited although an alternative explanation is that the substance is of low toxicity. Based on the inherent molecular weight, carbon number range, and lipophilicity it is expected that the registered substance will be minimally absorbed. This is supported by data from repeated dose studies for structurally analogous substances in which there were no treatment-related effects on organ weights or evidence of tissue histopathology that would provide any evidence of systemic absorption, distribution or metabolism of the test material. Chemicals that are absorbed from the gastrointestinal tract must pass through the liver (viathe portal vein) before they reach systemic circulation. Extensive absorption or repeated exposures can sometimes lead to adaptive changes in the liver resulting in increases in liver weight, detoxification-metabolism and hepatic enzyme induction. There were no such changes in the repeated oral dose study, suggesting that absorption is low or limited, even after repeated administration.  

A toxicokinetics study performed by Albro et al. (1970) evaluated absorption of hydrocarbon mixtures (n-paraffins C14-C28). Simple mixtures of aliphatic hydrocarbons were administered to rats by gastric intubation at dose levels of up to 500 mg/kg b. w. The percentage retention of the aliphatic hydrocarbons was inversely proportional to the number of carbon atoms ranged from 60% for C14 to 5% for C28 compound. The major site of absorption was found to be the small intestine.Using these data, the investigators developed an empirical relationship by which to predict gastrointestinal absorption in which percentage absorbed=115.9- (3.94)(number of carbon atoms). Using this relationship, the predicted absorption of the constituents of the registered substance ranges from 45% for the C18 constituent to 21% for the C24 constituent (approximately 33% overall).

In metabolism studies of C16 to C18 hydrocarbons (constituents of white oils, Albro, 1970), it was shown that the C16 and C18 hydrocarbons are metabolized to the fatty acids of the same carbon chain length as the partner hydrocarbons, suggesting a process of omega oxidation (Baldwin et al, 1992, Klimisch score=2).  

A toxicokinetic study performed by Ebert et al (1966) evaluated distribution of white or medicinal mineral oil (IP346<3%) administered orally via i. p. injections. Male and female rats were dosed with 0.66 mL of radiolabelled mineral oil for thirty-one consecutive days. Radioactivity was measured in extracted tissues after sacrifice. Results indicate that radioactivity is primarily found in liver, fat, kidney, brain and spleen. Both oral and i. p. routes of administration exhibited the same characteristics of absorption. Urine and feces were collected and stored daily for radioactivity analysis. 80% of the tritiated mineral oil administered orally was not absorbed but rather excreted in the feces two days after treatment. Only 11% of the total dose administered by i. p. injection was excreted in the feces during the first 8 days of the study.

A toxicokinetic study on structurally analogous substance of higher molecular weight conducted with 1-decene, homopolymer, hydrogenated, included four experimental procedures designed to assess the toxicokinetic profile of orally or intravenously administered3H-Nexbase 2006 FG in male rats (Runacres, 1999). Three rats/ dose were used for each time point and endpoint measured.

In experiment #1, male Fischer rats were administered a single oral dose of3H-Nexbase 2006 FG at doses of 30, 210, or 1500 mg/rat. Maximum plasma radioactivity was measured at 8, 4, and 72 hours, respectively, with mean concentrations of 0.893, 2.243 and 6.720 µg equivalents/ml. Terminal rate constants of 81 and 93 hours could only be estimated for the 210 and 1500 mg/rat doses. The majority of the dose remained in the gastrointestinal (GI) tract and was excreted in the faeces by 168 hours with ≥ 92% of the dose recovered. Excretion was rapid with nearly all radioactivity collected by 48 hours for animals dosed with 30 or 210 mg3H-Nexbase 2006 FG.  Excretion of the 1500 mg/rat dose took longer with radioactivity still collected at 168 hours. Urinary excretion were low (<1%). Although the majority of the dose was found in the gastrointestinal tract, radioactivity was also found in the liver, lymph nodes, fat, kidneys, and spleen.  Rats administered 210 or 1500 mg/rat3H-Nexbase 2006 FG had oily fur shortly after dosing (this was also noted by increasing amounts of radioactivity in the fur). While the oil was gone by morning in the 210 mg/rat group, it took 48-72 hours to decline after exposure to 1500 mg/rat. Very little of the administered oral dose of3H-Nexbase 2006 FG was considered absorbed in this experiment. 

In experiment #2, male Fisher rats were administered a single intravenous dose of3H-Nexbase 2006 FG (30 mg/rat). No pharmacokinetic analysis of plasma radioactivity was possible because the measured plasma radioactivity in 2 of the 3 rats was below the limits of quantification 4 hours post-dosing. 

In experiment #3, male Fischer rats were orally administered Nexbase 2006 FG (210 mg/rat/day) for 14 days followed by a single dose of3H-Nexbase 2006 FG. Mean overall recovery of radioactivity following repeated exposure to Nexbase 2006 FG was 94.88% (almost exclusively in the faeces) at 168 hours following the final dose of3H-Nexbase 2006 FG. The pattern of excretion of radioactivity at the 210 mg/rat level was almost identical to the single dose excretion study (Experiment 1).

In experiment #4, rats had bile duct-canulation surgery prior to oral administration of3H-Nexbase 2600 FG (210 mg/rat). The majority of the administered dose was recovered in the faeces (70.03%) and GI tract (24.76%) at sacrifice (48 hours post-dosing). Very little of the dose (mean 0.01%) was recovered in the bile. 

Collective analysis of the results from the toxicokinetic experiments with Nexbase 2006 FG indicates that it is not extensively absorbed from the gastrointestinal tract of rats following oral administration and the predominant route of excretion is via the faeces. Any material that is absorbed is likely to be cleared rapidly from the blood. These experimental findings correlate well with the predicted low degree of oral absorption of saturated hydrocarbon fluids, i. e., branched paraffins (also known as alkanes), such as 1-decene, homopolymer hydrogenated, with large molecular weights, low water solubility(< 0.1 mg/L), and large partition coefficient (log Kow > 6.5) (Walker and Mullee, 2006, ECHA Guidance Chapter R.7C). 

Discussion on absorption rate:

One toxicokinetic study was identified for a structurally analogous substance (ExxonMobil, 1993). This study conducted with 1-decene homopolymer, hydrogenated involved a single topical dose of 40mg test material (8mg/cm2skin surface) fortified with3H-labeled test material to determine the percutaneous absorption in rats. The topical dose was administered to the clipped dorsal surface of the animals and covered with a non-occlusive protective cell. After 24 h of exposure, the cell was removed and the dosed area wiped with olive oil. Urine and feces were collected at 24, 48, 72, and 96 hours post-dose. At the 96 hour time point, the animals were sacrificed and the amount of absorbed test material and its metabolites in the body was determined.  Nearly 18% of the applied dose was absorbed in the rats with 2.9, 4.9% and 9.8% of the applied activity present in the treated skin, tissues and excreta, respectively. The latter consists of 7.8% in the feces and 2.0% in the urine. Low levels of activity were found in the liver (0.5%), untreated skin (0.8%) and remaining tissues (0.8%).

Detailed substance identity details supporting the use of 1-decene homopolymer, hydrogenated (CAS No. 68037-01-4) as read-across can be found in ‘Section 13-Assessment Reports’ of the IUCLID dossier and in a read-across justification appended to the CSR.