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Additional information

There were no in vitro genetic toxicity studies available for 1 -decene trimer, hydrogenated and tetramers; therefore read across within category or to a structural analogue was used for all genetic toxicity in vitro endpoints. For gene mutation in bacteria, two read-across studies were identified, one from a structural analogue (Alkane 4) and another from 1 -decene, homopolymer, hydrogenated. For Alkane 4, mutagenicity was not observed in bacteria strains TA98, TA100, TA1535, and TA1537 of S. typhimurium and strain WP2uvrA of E. coli when exposed to Alkane 4 in Pluronic in ethanol (25% w/w) at concentrations of 0, 15, 50, 150, 500, 1500, or 5000 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method (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 lymphocytes in vitro when 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 cultured in vitro were 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 -decene trimer, hydrogenated and tetramers; 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 (Klimisch score=1) and another from a structural analogue (Alkane 4). 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 4, 5 mice/sex/dose were treated via intraperitoneal injection with Alkane 4 at doses of 0, 1250, 2500, or 5000 mg/kg bw (Durward, 1995). Bone marrow cells were harvested at 24, 48, and 72 hours post-treatment. The vehicle was Arachis Oil. Although there was a statistically significant increase in micronucleated cells at 24 hours at 5000 mg/kg; an increase was not observed at 48 or 72 hours; the results were within the historical control response and there was no dose response. The positive control induced the appropriate response. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time.

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 as an analogue. Alkane 4, like other compounds in this category, is a poly alpha olefin, i. e., highly branched isoparaffinic chemicals produced by oligomerization of oct-1 -ene, dec-1 -ene, and/or dodec-1-ene. Therefore its 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-decene, trimer, hydrogenated and tetramers. 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 weight of evidence approach, 1-decene trimer, hydrogenated and tetramers 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.