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Additional information

There were no in vitro genetic toxicity studies available for 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of sam M Wt); therefore read across within category or to a structural analogue was used for all genetic toxicityin vitroendpoints. For gene mutation in bacteria, two read-across studies were identified, one from a structural analogue (Alkane 5) and another from 1-decene, homopolymer, hydrogenated. In the study using Alkane 5, there were no significant increases in revertant colonies in strains TA1537, TA1535, TA100, and TA98 of S. typhimurium and Escherichia coli WP2uvrA either with or without metabolic activation when treated with various concentrations of Alkane-5 using an agar plate and incubated for 48 hours (Thompson, 1995). For 1-decene, homopolymer, hydrogenated, negative results were found for strains TA1535, TA1537, TA98, and TA100 of S. typhimurium and Escherichia coli strain WP2uvrA when exposed to a homogeneous emulsion of Silkflo 366 NF polydecene in surfactants, Sorbitan stearate and Polysorbate 60 at concentrations of 156.25, 312.5, 625, 1250, 2500, or 5000 μg/plate in the presence and absence of mammalian metabolic activation using the pre-incubation method (Cattanach, 1997).

 

Read across from Alkane 4 was used to assess the potential of cytogenicity in mammalian cells (Wright, 1995). Human lymphocyte cultures from a healthy volunteer were exposed to Alkane 4 in ethanol at concentrations of 0, 39, 78.1, 156.25, 31 2.5, 625, 1250, 2500 and 5000μg/mL with or without metabolic activation in the first experiment (Experiment 1) and at concentrations of 625, 1250, 2500 and 5000μg/mL (Experiment 2) for 20 hours or 1250, 2500, and 5000 μg/mL (Experiment 2) for a 44 hour harvest time.

 

Alkane 4 did not induce chromosomal aberrations or polyploidy cells with or without metabolic activation. Positive controls, ethyl methanesulfphonate in the absence of S9, and cyclophosphamide in the presence of S9, gave an appropriate response. Based on these results Alkane 4 is considered non-clastogenic to human lymphocytesin vitrowhen tested at concentrations ≤ 5000 µg/mL.

 

Read across from Alkane 4 also was used to assess the potential of gene mutation. In a study by Pant (2000), Chinese hamster ovary (CHO) cells culturedin vitrowere exposed to Alkane 4 in ethanol at concentrations of 0, 313, 625, 1250, 2500, or 5000 μg/mL in the presence and absence of mammalian metabolic activation (S9) for 4 hours.

 

At 625 μg/mL with metabolic activation, a significant response was observed; however, the increase was not significant when it was compared to the historical, cumulative solvent control data. The same was true for the test article concentration of 2500 µg/mL, with activation, in the confirmatory mutation assay. The increase in the number of mutants was not significant when compared to historical, cumulative solvent control data. The response seen in the definitive mutation assay at 625 μg/mL was not reproduced in the confirmatory assay. Thus, the test article Alkane 4 was not considered to have caused a significant increase in the mutant frequency at the HGPRT locus among the test article-treated cultures in the presence and absence of exogenous metabolic activation. There was no dose-dependent response in the test article treated cultures. The mutant frequencies of the test article solvent and the solvent for the positive controls were within the historical negative control values.

 

There were no in vivo genetic toxicity studies available for 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of sam M Wt); therefore read across within category or to a structural analogue was used to assess mutagenic potential. Two micronucleus read-across studies performed in mice were identified, one from 1-dodecene dimer with 1-decene, hydrogenated and another from a structural analogue (Alkane 5). For 1-dodecene dimer with 1-decene, hydrogenated, 18/sex/dose were treated with a single intraperitoneal injection of Oronite XS 101 at doses of 0, 1250, 2500, or 5000 mg/kg bw (Machado, 1989). Bone marrow cells were harvested at 24, 48, and 72 hours post-treatment from 5 mice/sex/group/time point. There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

 

For the study conducted using Alkane 5, groups of male and female CD-1 albino mice received a single intraperitoneal injection of 1250, 2500, or 5000 mg/kg Alkane 5 in arachis oil. Five animals of each sex were sacrificed at 24, 48, or 72 hours post-exposure. Similarly groups of ten mice (male & female) either received the arachis oil vehicle control or cyclophosphamide as positive control. Bone marrow smears were prepared and evaluated for micronucleated polychromatic erythrocytes (PCEs) and normochromatic erythrocytes (NCEs). There were no premature deaths or clinical observations in any of the treated animals. There was no statistically significant increase in micronucleated PCEs in the treated animals compared to the vehicle control nor was there a significant change in the PCE/NCE ratio. The positive control provided an appropriate response. Based on these results, Alkane 5 was considered to be non-genotoxic under the study conditions. 

 

Justification for Read Across

 

Several criteria justify the use of the read across approach to fill data gaps for poly alpha olefins using Alkane 4 and Alkane 5 as an analogue. Alkane 4 and Alkane 5, like other compounds in this category, are poly alpha olefins, i. e., highly branched isoparaffinic chemicals produced by oligomerization of oct-1-ene, dec-1-ene, and/or dodec-1-ene. Therefore their physiochemical and toxicological properties are expected to be similar to those of other poly alpha olefins.


Short description of key information:
There were no genetic toxicity studies identified for 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of sam M Wt). Read-across studies for in vitro gene mutation in bacteria (OECD 471), cytogenicity in mammalian cells (OECD 473), and gene mutation in mammalian cells (OECD 476) were identified within category or from structural analogues. Two read-across studies for in vivo gene mutation (OECD 474) were identified, one within category and another from a structural analogue.

All genetic toxicity tests, both in vitro and in vivo, were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All read-across in vitro genetic toxicity studies (i. e., gene mutation studies in bacteria; cytogenicity studies in mammalian cells; and gene mutation studies in mammalian cells) from substances within category or from structural analogues showed negative results. Identified in vivo mouse micronucleus studies also produced no evidence of mutagenic effects. Based on the results of the read-across studies, 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of sam M Wt) is unlikely to be mutagenic and does not meet the criteria for classification and labelling as described in EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.