1-Dodecene, mixed with 1-decene and 1-octene, dimers, hydrogenated

Endpoint summary

Description of key information

Repeated Dose Oral 28d, 2 key studies-NOAEL >= 1000 mg/kg for rats (OECD TG 407, limit test), read-across 1-decene dimer with 1-dodecene, hydrogenated; 1-dodecene dimer, hydrogenated
Repeated Dose Oral 90d, 2 key studies- NOAEL >= 20000ppm (~1250 mg/kg, highest dose tested) for rats (OECD TG 408), read-across 1-decene homopolymer, hydrogenated
Repeated Dose Dermal 90d, 1 key study- NOAEL >= 2000 mg/kg for rats (highest dose tested, OECD TG 411), read-across 1-decene homopolymer, hydrogenated

Additional information

There were no identified key studies for repeated oral, dermal or inhalation exposure to the registered substance. Read-across data on structurally related substances were used to assess repeated dose toxicity through oral and dermal exposure.  There were, however, no studies identified for repeated dose toxicity from inhalation exposure. 

Repeat Dose Oral

Two 28-day studies and two 90-day repeated dose studies for oral exposure identified for a structurally analogous substance are reported in this registration dossier. For the 28-day repeated dose endpoint, studies were identified from 1-decene dimer with dodecene, hydrogenated; and 1-decene dimer with dodecene, hydrogenated. For 90-day exposures, studies were identified from 1-decene, homopolymer, hydrogenated. All studies were considered robust and performed in a manner similar or equivalent to currently established OECD guidelines.  Summaries of these studies are presented below.

 

Overall, the 28-day exposure studies produced no mortalities or significant clinical or systemic toxicity when the respective hydrogenated poly alpha olefins were administered orally. In the first 28-day repeated dose studies (Chevron, 1995g), 1-dodecene dimer, hydrogenated was administered to Sprague-Dawley rats (5 sex/dose) by oral gavage for four weeks at nominal concentrations of 0, and 1000mg/kg (limit test). Two additional satellite groups were similarly dosed with 0 and 1000mg/kg/day and allowed to recover for two weeks after 28 days of dosing before being sacrificed.  No mortality or treatment-related clinical signs were observed in the test or control animals throughout the study. There were no changes in body weight gain, food consumption, hematology, or clinical chemistry.  Organ weights were not affected by treatment.  No treatment-related histopathological changes were observed in the examined tissues of the treated animals at time of necropsy. The NOAEL is therefore considered to be greater than 1000 mg/kg bw /day in orally exposed rats for 28 days (limit dose).  In the second 28-day repeated dose study (Chevron 1989e), 1-decene dimer with dodecene, hydrogenated was administered to six Sprague-Dawley rats/sex/dose at dose levels 0, 200, 500, or 1000 mg/kg bw/day for 29 days. A recovery group (6 rats), dosed with 0 or 1000 mg/kg/day of the test substance, was observed for two weeks post-dosing. No mortality, compound-related systemic toxicity or pathological changes were observed in the study or recovery groups at the limit dose of 1000 mg/kg. Statistically significant changes were observed in food consumption, haematology, serum chemistry, and organ weights for a given dose or sex. However, none of the changes were considered to be of toxicological significance for one or more of the following reasons: the change did not occur in both sexes, it was not dose dependent, it did not correlate with any change in histopathology, and/or it was within clinically normal limits. No LOAEL could be determined due to lack of any affects. The NOAEL was reported as 1000 mg/kg/day. 

 

In a 90 day study (ExxonMobil, 1994b), 1-decene homopolymer, hydrogenated was administered in the diet to groups of 10 male and 10 female Fischer 344 rats at dose levels of 0, 200 and 20000ppm for a minimum of 90 days.  No animals died or were sacrificed prior to the scheduled necropsy.  The test material did not affect body weight gain.  In general, the amount of food consumed by animals exposed to test material was comparable to that of control animals.  No clinical signs indicative of systemic toxicity or adverse effects on hematology parameters were observed.  After thirteen weeks of treatment, statistically significant differences were observed between the serum chemistry data from the control group and treated groups for glucose in males and for sodium, phosphorous, and calcium in females.  However, these changes were not considered toxicologically significant by the study director for one or more of the following reasons; it was not consistently observed in both sexes, it was not dose dependent, it did not correlate with any histopathological changes. No remarkable findings were observed at necropsy.  Based on these data, the NOAEL for the test material administered in the diet to rats was greater than or equal to 20000ppm (1250 mg/kg/bw/d).

 

In a second 90d study (ExxonMobil, 1991a), 1-decene homopolymer, hydrogenated was administered in the diet to groups of 20 male and 20 female Sprague-Dawley rats at dose levels of 0, 500, 5000 and 20000 ppm for thirteen weeks.  No animals died or were sacrificed prior to the scheduled necropsy.   The test material did not adversely affect the amount of food consumed by exposed animals or body weight gain.  The urinalysis and ophthalmologic exam data showed no treatment-related effects.  No clinical signs indicative of systemic toxicity or adverse effects on hematology parameters were observed.    After thirteen weeks of treatment, statistically significant differences were observed between the serum chemistry data from the control group and treated groups for albumin/globulin ratio and globulin in males and for inorganic phosphorous in females. When historical serum reference values were considered, only the dose-response curve for inorganic phosphorous at 20000 ppm fell outside the normal range. This finding, without concomitant decrease in serum calcium levels or supportive pathology, was judged not to be biologically significant by the study director. In general, there were no statistically significant differences in the absolute or relative organ weight data which could be attributed to exposure to the test material.  Based on these data, the NOAEL for the test material administered in the diet to rats was determined to be greater than or equal to 20000 ppm (or approximately 1250 mg/kg bw/d).

 

To further support the hazard conclusions and read-across approach, data for the aliphatic hydrocarbon solvents with carbon numbers in the range of 9-20 were also considered (i.e. C9-C14 Aliphatics, <2% Aromatics Category and C14-C20 Aliphatics, <2% Aromatics Category, together defined in this document as ‘C9-C20 Hydrocarbon Solvents‘). Whereas, 1-decene homopolymer; 1-decene dimer, hydrogenated; and 1-decene dimer with dodecene, hydrogenated represent aliphatic hydrocarbons of higher carbon number and molecular weight compared to the registered substance, the C₉-C₂₀Hydrocarbon Solvents are of immediate lower carbon number and molecular weight to the registered substance (refer to the read-across justification appended to the CSR for more details).  As was observed following oral exposure to 1-decene homopolymer, hydrogenated; sub-chronic (90 days) toxicity studies that examine toxicity by the oral route for the C₉-C₂₀Hydrocarbon Solvents, support a NOAEL >1000 mg/kg bw/day, indicating a low order of toxicity via the oral route of exposure for these substances (OECD TG 408). The data for the C₉-C₂₀Hydrocarbons Solvent substances has been previously submitted to ECHA as part of a number of individual substance registrations, including:

-         Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 08: C9-C14 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119463258-33-0000.

-         Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 09: C14-C20 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119457735-29-0000). 

As described in section R.6.2 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’ (ECHA, 2008e) relevant information in support of the target chemical contained within an existing assessment (i.e. the substance is already registered) need only be referenced. Therefore these data are not provided as individual study reports within this assessment, but are summarized and referenced in the read-across justification appended to the CSR for this substance.

 

The provided read-across data for the aliphatic hydrocarbon substances described above (i.e. C9-C20 Hydrocarbon Solvents; 1-decene dimer, hydrogenated; 1-decene dimer with dodecene, hydrogenated; and 1-decene dimer, homopolymer) span across a broad range of carbon numbers within which the registered substance falls (refer to the read-across justification appended to the CSR for further details). All of these substances are hydrocarbons consisting primarily of aliphatic constituents (i.e. the only functional groups are alkyl side chains). The provided read-across data clearly demonstrate that aliphatic hydrocarbons within this carbon number range have a low potential for toxicity for this endpoint. Therefore, it is scientifically reasonable to conclude that the registered substance also has a low potential for toxicity for this endpoint. The Registrant is of the scientific opinion that the read-across data are adequate and useful for the purpose of hazard and risk assessment for the registered substance and support the conclusion that classification of the registered substance for this endpoint under EU GHS guidelines and classification under EU requirements for dangerous substances and preparations guidelines are not warranted.

 

Repeat Dose Dermal

One 90-day repeated dose study for dermal exposure was identified for a structurally analogous substance 1-decene, homopolymer, hydrogenated. This study was considered robust and performed in a manner similar or equivalent to currently established OECD guidelines.  A summary of this study is presented below.

 

In the 90 day study (ExxonMobil, 1985a), 1-decene homopolymer, hydrogenated was administered dermally to rats (15 males and 15 females per group) at concentrations of 0, 800, and 2000 mg/kg, five days per week for 13 weeks. Only a very slight effect on the skin at the site of application was seen during the study.  No effects on hematology, serum chemistry, urinalysis, organ weights or histopathology were observed.  A statistically significant decrease in body weight compared to controls was seen in males treated with 2000mg/kg/day from Day 37 until the end of the study (with one exception).  However the mean weights were within 10% of those of controls, and no effect was observed in females at this dose.  Based on these findings, the NOAEL was determined to be greater than or equal to 2000mg/kg/day.

 

To further support the hazard conclusions and read-across approach, data for the aliphatic hydrocarbon solvents with carbon numbers in the range of 9-20 were also considered (i.e. C9-C14 Aliphatics, <2% Aromatics Category and C14-C20 Aliphatics, <2% Aromatics Category, together defined in this document as ‘C9-C20 Hydrocarbon Solvents‘).. Whereas, 1-decene homopolymer represents a hydrocarbon of higher carbon number and molecular weight compared to the registered substance, the C₉-C₂₀Hydrocarbon Solvents are of immediate lower carbon number and molecular weight to the registered substance (refer to the read-across justification appended to the CSR for more details).  In a 90 day repeat dose study, a NOAEL of > 495 mg/kg bw/day was observed, which was the highest dose tested (REACH 2010a, 2010b). The data for the C₉-C₂₀Hydrocarbons Solvents category of substances has been previously submitted to ECHA as part of a number of individual substances, including:

-     Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 08: C9-C14 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119463258-33-0000.

-     Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 09: C14-C20 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119457735-29-0000). 

 

As described in section R.6.2 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’ (ECHA, 2008e) relevant information in support of the target chemical contained within an existing assessment (i.e. the substance is already registered) need only be referenced. Therefore these data are not provided as individual study reports within this assessment, but are summarized and referenced in the read-across justification appended to the CSR for this substance.

 

The provided read-across data for the aliphatic hydrocarbon substances described above (i.e. C9-C20 Hydrocarbon Solvents and 1-decene dimer, homopolymer) span across a broad range of carbon numbers within which the registered substance falls (refer to the read-across justification appended to the CSR for further details). All of these substances are hydrocarbons consisting primarily of aliphatic constituents (i.e. the only functional groups are alkyl side chains). The provided read-across data clearly demonstrate that aliphatic hydrocarbons within this carbon number range have a low potential for toxicity for this endpoint. Therefore, it is scientifically reasonable to conclude that the registered substance also has a low potential for toxicity for this endpoint. The Registrant is of the scientific opinion that the read-across data are adequate and useful for the purpose of hazard and risk assessment for the registered substance and support the conclusion that classification of the registered substance for this endpoint under EU GHS guidelines and classification under EU requirements for dangerous substances and preparations guidelines are not warranted.

 

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 with dodecene, hydrogenated; and 1-dodecene dimer, hydrogenated as analogues substances. These substances are all hydrogenated poly alpha olefins, i.e., 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 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 (as much as 95% C20 and C22). 

 

Several criteria justify the use of the read-across approach to fill data gaps for the registered substance using the analogous substances 1-decene homopolymer, hydrogenated. Both 1-decene homopolymer, hydrogenated and the registered substance are fully saturated hydrocarbon fluids, i.e., 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. One important distinction between these two substances is the molecular weight (i.e. carbon number). The registered substance consists of minimally branched paraffins of carbon numbers ranging from C18-C24 (at least 85% C20-C22), whereas 1-decene homopolymer, hydrogenated consists of branched paraffins ranging in carbon number C30-C60 (primarily C30-C40). In this instance, reading across from a higher molecular weight substance to an analogous substance of lower molecular weight is scientifically supportable, particularly upon consideration of data on aliphatic hydrocarbons with carbon numbers ranging from C9-C20 (‘C9-C20 Hydrocarbon Solvents’). This reasoning is briefly described below and clarified in further detail in the read-across justification appended to the CSR.

 

 

The registered substance (a minimally branched paraffin with carbon numbers in the range of C18- C24, at least 85% C20, C22) and 1-decene dimer homopolymer, hydrogenated (a branched paraffin with carbon numbers in the range of C30-C60, at least 85% C30, C40) can be considered as essentially composed of synthetically manufactured hydrocarbons that are compositionally more precisely defined than the distilled hydrocarbons within the Hydrocarbon Solvents Category. Fundamentally, high molecular weight aliphatic hydrocarbon solvents could be viewed at the low end of a continuum with 1-decene homopolymer, hydrogenated (C30-60) in regards to physical/chemical properties and toxicokinetic properties. Therefore, providing information for substances on the low end of the continuum as well as the high end of the continuum will bracket the registration substance with data and provide insight into the scientific logic supporting the reasonable expectation of similar effects between the registered substance and 1-decene homopolymer, hydrogenated. The Registrant is of the scientific opinion that the similarity in molecular structure, and trend in toxicokinetics which provide 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 homopolymer, hydrogenated are appropriate for the purposes of hazard

 

The data for the Hydrocarbons Solvents Category of substances has been previously submitted to ECHA as part of a number of individual substance registrations, including:

-         Hydrocarbons, C9-C11, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 08: C9-C14 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119463258-33-0000.

-         Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics.Part of Category 09: C14-C20 Aliphatics, <2% Aromatics Category. Registration Reference Number: 01-2119457735-29-0000). 

 

As described in section R.6.2 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’ (ECHA, 2008e) relevant information in support of the target chemical contained within an existing assessment (i.e. the substance is already registered) need only be referenced. Therefore these data are not provided as individual study reports within this assessment, but are summarized and referenced in the read-across justification appended to the CSR for this substance. 

 

 

A legislative goal of the REACH Regulation is to avoid unnecessary animal testing through promotion of replacement, reduction, or refinement of testing on vertebrate animals. Article 13 of the REACH regulation (EC) 1907/2006 states ”Information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods”. The use of read-across data is one mechanism identified in Annex XI as an appropriate alternative method for fulfilling information requirements. It is the Registrants scientific opinion that the available read-across information demonstrating that saturated aliphatic hydrocarbons ranging in carbon numbers from C9 to C60 have a low potential for toxicity for this endpoint is ample evidence to support a rational judgment regarding hazard identification, classification and labeling and risk assessment for the registered substance (with a carbon number range of C18-C24). It is the Registrants scientific opinion that no new information will be gained through additional testing in vertebrate animals.

Justification for classification or non-classification

The provided read-across data demonstrate that aliphatic hydrocarbons ranging in carbon numbers from C9 to C60 have a low potential for toxicity for this endpoint. These data provide ample evidence to support a rational judgment regarding hazard identification, classification and labeling, and risk assessment for the registered substance (having a carbon number range of C18-C24). Therefore, it is scientifically reasonable to conclude thatthe registered substance does not meet the criteria for classification as a repeated dose toxicant under the EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.