Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

There were no in vitro genetic toxicity studies available for the registered substance; therefore read across to structural analogues was used for all genetic toxicity in vitro endpoints. Overall, the data support that the registered substance is not mutagenic in vitro or in vivo

Genetic toxicity in vitro- bacteria

For gene mutation in bacteria, three key studies were identified for analogous substances; 1-decene dimer, hydrogenated; 1-decene dimer with dodecene, hydrogenated; and 1-dodecene dimer, hydrogenated. In all three studies, there were no significant increased in revertant colonies in any of the strains tested with or without metabolic activation (ExxonMobil, 1989a; Chevron 1995h; Chevron, 1989f). 

Based on these data, the registered substance is not expected to be mutagenic

Genetic toxicity in vitro- mammalian cytogenicity

In accordance with column 2 of REACH Annex VIII, the in vitro cytogenicity study (required in section 8.4.2) does not need to be conducted because adequate data from an in vivo cytogenicity test are available.

Based on the in vivo cytogenicity data, the registered substance is not expected to be genotoxic.

Genetic toxicity in vitro- mammalian gene mutation

Data on the gene mutation potential in mammalian cells for the registered substance were not located. However, based on qualitative weight of evidence, the substance is not expected to be mutagenic. All of the evidence presented below to support the Annex VIII section 8.4.3 information requirement should be considered in totality as part of an adaptation of the required standard information set out in Annex VII-X according to the general rules contained in Annex XI section 1.2. The information should not be considered on an individual basis when determining its adequacy. When considered in totality, the combined evidence is appropriate and adequate to draw a conclusion about the properties or the potential effects of the registered substance for this endpoint.

Although an in vitro mammalian gene mutation study on the registered substance has not been conducted, there are data from related studies of several types to support a reasonable conclusion about the properties or the potential effects of the registered substance for this endpoint.

1. An in vitro mammalian gene mutation study (CONCAWE, 1985)on an analogous substance observed no mutagenic activity in the presence and absence of metabolic activation. These data suggested the registered substance is not mutagenic in mammalian cells.

2. There are three in vitro gene mutation studies in bacteria on analogous substances (ExxonMobil, 1989a; Chevron 1995h; Chevron, 1989f). In all cases, the test material did not induce mutagenic effects with and without metabolic activation providing supportive evidence that the registered substance (including potential metabolites) is not mutagenic in vitro.

3. There are two in vivo mouse bone marrow micronucleus assays on structurally analogous substances (ExxonMobil, 1989b, 1995c). In both cases, mutagenic effects were negligible supporting the conclusion that the registered substance is not expected to be genotoxic in mammalian cells.

4. Published studies of lower molecular weight isoparaffins (C10-C16) report negative results in an in vitro mammalian gene mutation assay (OECD 2003a, 2003b).

5. The registered substance is a fully saturated hydrocarbon fluid with no reactive functional groups to indicate mutagenic potential.

The available information summarized above, which individually, may not be adequate in themselves to meet the information requirement provides reliable, relevant and adequate information for assessing this endpoint when considered together. Based on these data, it is not expected that the registered substance is mutagenic. The data are described in more detail below and the reliability, relevance and adequacy evaluated.

An in vitro mammalian gene mutation study was identified for the analogous substance, white mineral oil (CONCAWE, 1985). In this study, mouse lymphoma L5178Y cells cultured in vitro were exposed to white mineral oil at concentrations ranging from 10-1000 ug/ml with and without metabolic activation. The mineral oil was found to be negative under these conditions. This study is directly relevant for fulfillment of the information requirement as it was performed by test guideline OECD 476, however the methods and results were reported with limited detail limiting the reliability score (Klimisch score=4).  The use of the read-across from white mineral oil to the registered substance is relevant based on structural similarity as described below in the read-across justification and in further detail in the justification appended to the CSR. Therefore this study contributes to the weight of evidence supporting that the registered substance is not expected to be mutagenic in mammalian cells.

In bacterial gene mutation assays, three structural analogues (1-decene dimer, hydrogenated; 1-dodecene dimer hydrogenated; and 1-decene dimer with 1-dodecene, hydrogenated) were not mutagenic in Salmonella strains tested in the presence or absence of metabolic activation (ExxonMobil, 1989a, Chevron 1995h, 1989f) .  Similarly, 1 -decene dimer with 1-dodecene, hydrogenated was not mutagenic in E. coli.  These data are reliable without restriction (Klimisch score=1) as they were performed following test guidelines similar or equivalent to OECD 471, are GLP studies, and are well-documented study reports. The use of the read-across from the above mentioned hydrocarbons to the registered substance is appropriate based on a number of unifying considerations as described below in the read-across justification and in further detail in the justification appended to the CSR. Furthermore, these data in bacterial cells are relevant to the endpoint of concern as they provide supportive evidence that the registered substance (including potential metabolites) is not mutagenic in vitro. Therefore these data add to the weight of evidence supporting that the registered substance is not expected to be mutagenic in mammalian cells.

In two in vivo mouse bone marrow micronucleus assays, the structural analogues 1-decene dimer, hydrogenated; and 1-dodecene dimer, hydrogenated tested negative for micronucleus induction (ExxonMboil, 1989b, 1995c).  All studies were conducted in a manner similar or equivalent to currently established OECD guidelines, are GLP studies and are well documented study reports (Klimisch score=1). The use of the read-across from the above mentioned hydrocarbons to the registered substance is appropriate based on a number of unifying considerations as described below in the read-across justification and in further detail in the justification appended to the CSR. Furthermore, these in vivo data provide supportive evidence that the registered substance (including potential metabolites) is not genotoxic in vivo. Therefore these data add to the weight of evidence supporting that the registered substance is not expected to be mutagenic in mammalian cells.

To further support the hazard conclusions, published studies of lower molecular weight isoparaffins (C10-C16) were also considered (OECD 2003a, 2003b). These data were reported in the SIDS Initial Assessment Report for the Higher Olefins Category. This Category consists of nine members: C6, C7, C8, C9, C10, C12 and C10-13 internal olefins and C16 and C18 linear alpha olefins. These substances are described as predominantly linear olefins, but may contain a small amount of branched material as impurities. Two OECD 476 equivalent studies were reported for the C10-C16 isoparaffins. In the first study, a blend of linear 1-dodecene (CASRN 112-41-4); 1-tetradecene CASRN 1120-36-1) and 1-hexadecene (CASRN 629-73-2) did not induce mutation in the HGPRT gene in CHO-K1 cells with and without metabolic activation. Likewise, in a second study a blend of linear 1-dodecene (CASRN 112-41-4), 1-tetradecene (CASRN 1120-36-1) and 1-hexadecene (CASRN 629-73-2) was not mutagenic with and without metabolic activation. These data are directly relevant for fulfillment of this information requirement as the tests were performed by methods similar to test guideline OECD 476, demonstrating these substances are not mutagenic in mammalian cells in vitro. However, the methods and results were reported with limited detail limiting the reliability score (Klimisch score=4). The use of the read-across from the Higher Olefins Category to the registered substance could somewhat be considered to represent a “worse case” based on their chemistry (see read-across discussion below for more detail). While the registered substance does not fall into the Higher Olefin Category definition, these data provide additional support and strengthen the weight of evidence that the registered substance (including potential metabolites) is not mutagenic.

As stated in the ECHA Practical guide 2: How to Report Weight of Evidence (ECHA, 2010), in the evaluation process of all available information according to Annex VI step 1 of the REACH regulation, data from sources other than tests specifically addressing an endpoint and described in Annex VII-X can be applied in weight of evidence. This includes the use of information from sources other than tests specifically addressing an endpoint to help support a conclusion. The below information from endpoints not specifically addressing mutagenicity adds to the weight of evidence supporting the low mutagenic potential of the registered substance.

Consideration of the chemistry of the registered substance suggests that it is inherently un-reactive. The registered substance is a fully saturated hydrocarbon fluid with no reactive functional groups and therefore is anticipated to have low mutagenic potential. Furthermore, as described in Section 7.1 – Toxicokinetics of the IUCLID dossier, saturated hydrocarbons, like those that constitute the registered substance, have limited absorption, but, if absorbed, would be efficiently metabolized to likely saturated fatty acids which, in turn, are rapidly conjugated and excreted. Therefore, the generation of reactive metabolites from saturated alkane hydrocarbons is highly unlikely and the above in vitro and in vivo genotoxicity data on structural analogues support this conclusion. 

The available information described above, which individually, may not be adequate in themselves to meet the information requirement provides reliable, relevant and adequate information for assessing this endpoint when considered together. The basic chemistry of the registered substances identifies this substance as inherently unreactive and therefore suggests the substance has low mutagenic potential. The above genotoxicity data consistently supports this conclusion by demonstrating that structurally analogous substances (and their potential metabolites) across a wide carbon number range (within which the registered substance falls) are not mutagenic in vitro or in vivo.  This cumulative weight of information is directly relevant to this endpoint. Therefore a rational judgment can be made regarding the hazard identification, classification and labeling and risk assessment for this endpoint. Based on these data, the registered substance is not expected to be mutagenic in vitro and no new information will be gained through additional testing.

Genetic toxicity in vivo

No in vivo genetic toxicity data were found for the registered substance. However, two key studies were identified for analogous substances; 1-decene dimer with dodecene, hydrogenated; and 1-dodecene dimer, hydrogenated. The results of these studies indicated negligible mutation potential of the registered substance.

In the first study (Chevron 1989g), 1-decene dimer with dodecene, hydrogenated was examined for its potential to induce chromosomal damage in mouse bone marrow erythrocytes in mice dosed interperitoneally at doses of 250, 2500 and 5000 mg/kg. Vehicle and positive control animals received peanut oil and triethylenemelamine, respectively. Bone marrow was collected from 10 animals (5/sex) from each treatment and vehicle control group at 24, 48, and 72 hours after administration. Positive controls were sampled at 24 hours.  No clinical signs of toxicity were observed during the study. Cytotoxicity was detected in males in the positive control and at the 1250 mg/kg dose level sampled at 24 hours and in females at the 2500 and 5000 mg/kg dose levels sampled at 48 hours. No significant increase in the number of micronucleated polychromatic erythrocytes was observed in any treated group when compared to control animals. The positive control induced micronuclei as expected.  The test material was considered to be non-genotoxic and non-clastogenic under the conditions of this test.

In the second study (Chevron, 1995i), 1 -Dodecene dimer, hydrogenated was examined for its potential to induce chromosomal damage in bone marrow erythrocytes in mice dosed interperitoneally with at doses of 1250, 2500 and 5000 mg/kg. Vehicle and positive control animals received arachis oil and cyclophosphamide, respectively. A small statistically significant increase in the number of micronucleated polychromatic erythrocytes (PCE) was observed at 48 hrs at 2500 mg/kg compared to concurrent controls. However, this increase was not part of a dose-related effect and was within the current historical control range and therefore, considered to be spurious and of no toxicological significance. Overall, there was no statistically significant change in the PCE/NCE ratio in any of the test material dose groups when compared to their concurrent vehicle control groups. The positive control material (cyclophosphamide) produced a marked increase in the frequency of micronucleated PCE when compared to the concurrent vehicle control group. The test material was considered to be non-genotoxic and non-clastogenic under the conditions of the test.

Based on the above in vivo cytogenicity data, the registered substance is not expected to be genotoxic.

Read across justification

Several criteria justify the use of the read-across approach to fill data gaps for the registered substance using 1-decene dimer, hydrogenated; 1-decene dimer with dodecene, hydrogenated; and 1-dodecene dimer, hydrogenated as analogues substances. These substances are all fully saturated hydrocarbon fluids, i. e., minimally branched paraffins (also known as alkanes) produced by oligomerization of 1-octene, 1-decene, and/or 1-dodecene. As described in the read-across justification appended to the CSR, these substances are similar in molecular structure, physicochemical properties, use, and manufacturing processes. Furthermore, data provided in CSR section 5.1 (IUCLID chapter 7.1) support similar toxicokinetic behavior of these minimally branched paraffins within this small carbon number range. Based on these unifying considerations, the slight difference in carbon number among these analogues is not expected to significantly impact mammalian toxicity. Therefore, it is scientifically reasonable to predict the toxicological properties for the registered substance from the properties determined for the analogues.

The nature of the read-across approach utilized here is aligned with the analogue approach as described in section R.6.2.3 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’ (ECHA, 2008e). The similarity among molecular structure and molecular weight which provides the basis for the read-across justification is scientifically founded and therefore adequately clarifies why the properties of the registered substance may be predicted from the properties of the read-across substance(s) and more specifically, why the data submitted for 1-decene, hydrogenated (C20); 1-decene dimer with dodecene, hydrogenated (C20-C24); and 1-dodecene dimer, hydrogenated (C24) are appropriate for the purposes of classification and labeling and/or risk assessment of the registered substance which contains similar molecules with carbon numbers in the ranges of 18 – 24 carbon atoms (at least 85% C20 and C22). 

The read-across justification for white mineral oil is based on structural similarity. Additional information regarding substance identity on white mineral oil can be found in the read-across justification appended to the CSR as well as in the dossier for white mineral oil previously submitted as part of the Highly Refined Base Oil Category. Both white oils and the registered substance are base oils produced from refining crude oil (in which the highly refined white mineral oil is yielded) or through chemical synthesis (the registered substance). From a regulatory perspective white mineral oil (CASRN 8042-47-5) is recognized as a UVCB substance consisting predominantly of saturated hydrocarbons (normal, branched, and cyclic) with carbon numbers predominantly in the range of C15-C50. White mineral oils may also contain low levels of aromatic constituents, but the aromatic constituents are reduced to very low levels to meet technical specifications for oils of this type. The registered substance, like white mineral oil, is comprised of saturated hydrocarbons with similar carbon numbers. It differs from white mineral oils in that, because of the way the registered substance is manufactured, the hydrocarbons are all minimally branched paraffins, with defined carbon numbers (e. g. C20, C22) rather than covering a range, and it does not contain aromatics or other impurities which may be found at trace levels in white mineral oils. Accordingly, white mineral oils could be considered to represent a “worse case” by comparison to the registered substance and are appropriate and relevant data to consider to support the hazard assessment of the registered substance. The Registrant is of the scientific opinion that the similarity in molecular structures composing white mineral oil and the registered substance is scientifically founded and therefore adequately clarifies why the properties of the registered substance may be predicted from the properties of the read-across substance.

The read-across justification for lower molecular weight isoparaffins (C10-C16) is based on structural similarity. These substance belong to the Higher Olefins Category and more information on the chemistry including physical chemical properties can be found in the SIDS Initial Assessment Report for the Higher Olefins Category (OECD, 2003). The Higher Olefins Category consists of nine members: C6, C7, C8, C9, C10, C12 and C10-13 internal olefins and C16 and C18 linear alpha olefins. These substances are described as predominantly linear olefins, but may contain a small amount of branched material as impurities. The data presented in the Higher Olefins Category document support the conclusion that within the C6 to C24 boundaries identified, that changing carbon number, location of the double bond or addition of branching does not alter the mammalian health and endpoints. Like the registered substance, these substances are hydrocarbons with no reactive functional groups. Unlike the registered substance, the Higher Olefins Category of substances are of lower molecular weight, contain a carbon-carbon double bond and are metabolized to a transient epoxide intermediate. Therefore, these substances could be considered to represent a “worse case” by comparison to the registered substance and are appropriate to consider in the cumulative weight of evidence. Note that the ability to provide a high level of detailed compositional information here is limited due to the publicly available nature of the data. Further data on physical/chemical properties and trends in toxicity data can be found in the SIDS document (OECD, 2003).   


Short description of key information:
In vitro gene mutation in bacteria, 3 key studies – negative in bacterial reverse mutation assay (OECD TG 471), read-across from 1-decene dimer, hydrogenated; 1-decene dimer with 1-dodecene, hydrogenated; 1-dodecene dimer hydrogenated
In vitro, gene mutation mammalian- No data available. No testing required based on qualitative weight of evidence reasoning.
Genetic Toxicity in vivo – negative in micronucleus assay in mouse (OECD TG 474), read-across from 1-decene dimer with 1-dodecene, hydrogenated

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The negative results in in vitro and in vivo genotoxicity assays do not warrant the classification of the registered substance as genotoxic under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.