Dodecene

Endpoint summary

Additional information

There were no in vitro genetic toxicity studies available for single carbon number isomerised olefins; therefore read across was made to linear alpha olefins (hex-1-ene) and multiple carbon number isomerised olefins (alkenes, C10/C11/C12/C13). Two studies were available for multiple carbon number isomerised olefins, C10/C11/C12/C13. The first study evaluated gene mutation in bacteria. According to the study report (Brooks and Wiggens, 1983), alkenes, C10/C11/C12/C13 were not mutagenic in Salmonella typhimurium strains, TA1537, TA1535, TA100 and TA98 and Escherichia coli WP2 uvrA, both in the presence and absence of rat liver fraction S9, at 31.25, 62.5, 125, 250, 500, I000, 2000 or 4000 µg per plate. The test material was also tested in Saccharomyces cerevisiae and did not cause an increase in the reverse mutation rates in yeast in the presence or absence of metabolic activation. In the other study on alkenes, C10/C12/C13/C14 did not induce chromosomal damage when tested up to 25µg/mL in a rat liver assay (Brooks and Wiggins, 1983).

 

One study evaluating the gene mutation potential of a hex-1-ene (linear alpha olefins) in mammalian cells was identified (Adams, 1990, Klimisch score=1). Hex-1-ene, diluted in DMSO, was examined in a mouse lymphoma thymidine kinase assay using L5178Y (TK+/-) cells (Adams et al, 1990). Prior to the main mutation study, a preliminary study was conducted with the test substance to determine its potential to cause cytotoxicity and also to determine an appropriate range for the main mutation study. Study protocols for both the preliminary and main study were similar with minor modification made in the main study. Based on experimental results, hex-1-ene was considered cytotoxic at doses = 300 µg/ml and was not mutagenic at concentrations =300 µg/mL either in the presence or absence of metabolic activation.

 

There were no in vivo mutagenic studies available for single carbon number isomerised olefins; therefore read across was made to linear alpha olefins and multiple carbon number isomerised olefins. In the read-across study from hex-1-ene (Harnois, 1983), 5 mice/sex/dose were treated (whole body inhalation exposure) with Gulftene 6 at doses of 0; 1000; 10,000; or 25,000 parts per million for a period of 2 hours on two consecutive days. Lethargy and rapid respiration were observed in animals treated at 10,000 and 25,000 ppm but these clinical effects were reversible post-exposure. Female mice (50%) exhibited statistically lower mean body weights on days 1 and 3. However, mean body weights of the remaining female mice were observed to be normal when compared to corresponding control animals. No significant increase in the frequency of micronucleated polychromatic erythrocytes in the bone marrow was noted after treatment at any dose level. Male and female animals induced with cyclophosphamide exhibited a statistically higher frequency of micronucleated polychromatic erythrocytes in the bone marrow when compared with negative controls.

 

In a read across study from multiple carbon number isomerised olefins, mice dosed intraperitoneally with 500, 1000, or 2000 mg/kg bw of alkenes, C20-24 showed no evidence of increased incidence of micronucleated polychromatic erythrocytes (Durward, 1998).

 

Based on the lack of observed mutagenic effects in in vitro and in vivo studies with linear alpha olefins and multiple carbon number isomerised olefins, it is unlikely that single carbon number isomerised olefins, including decene, are mutagenic. Based on these findings, decene does not meet the EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for mutagenicity.

 

Justification for Read Across:

Several criteria justify the use of the read across approach to fill data gaps for single carbon number isomerised olefin substances using linear alpha olefin substances. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter effects on mammalian health endpoints. There is a consistent toxicity potency pattern for individual alpha olefins supported by a low toxicity concern for acute oral, dermal and inhalation exposure. These materials are slightly irritating to skin and mildly irritating to non-irritating to eyes of rabbits. In repeat dose toxicity studies, hex-1-ene and tetradec-1-ene have shown comparable levels of low toxicity, with female rats exhibiting alterations in body and organ weights and changes in certain haematological values at the higher doses tested; male rats exhibiting nephropathy presumed to be associated with the alpha2u-globulin protein. Screening studies indicate that they are not neurotoxic (for hex-1-ene and tetradec-1-ene), do not produce adverse effects on reproduction or foetal development (hex-1-ene and tetradec-1-ene), and are not genotoxic (hex-1-ene, oct-1-ene, dec-1-ene, dodec-1-ene, and tetradec-1-ene). Study results for the aforementioned endpoints indicate a low hazard potential for human health. Since the addition of branching does not measurably alter the results of studies on mammalian health endpoints, there should not be any significant toxicological differences between substances in single carbon number isomerised olefins and linear alpha olefins.  Therefore, read across between these two categories can be justified.

 

Several criteria justify the use of the read across approach to fill data gaps for single carbon number isomerised olefin substances using multiple carbon number isomerised olefin substance analogues. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter the effects on mammalian health endpoints. There is a consistent toxicity potency pattern for isomerised olefins with a range of carbon numbers and they are considered to have minimal acute toxicity potential. Genotoxicity studies indicate that these materials are not mutagenic. No adverse systemic toxicity was observed in a 90-day repeated oral dose study in which rats were exposed to alkenes, C20-24. The toxicological profile of multiple carbon number isomerised olefins described above indicates a low hazard potential for human health. Since multiple carbon number isomerised olefins, alkenes is comprised of a mixture of single carbon number isomerised olefins, no significant toxicological differences are expected between the two categories of substance and read across between these two categories can be justified.

Short description of key information:
There were no genetic toxicity studies identified for isomerised olefins; alpha, internal, linear and branched - single carbon number. Read-across studies for in vitro gene mutation in bacteria (OECD 471) and cytogenicity in mammalian cells (OECD 473) from isomerised olefins; alpha, internal, linear and branched – multiple carbon numbers were identified. A read-across study (OECD 476) within Category for in vitro gene mutation in mammalian cells was used from linear alpha olefins. Two read-across studies (OECD 474) for in vivo gene mutation were identified, one from linear alpha olefins and one from multiple carbon number isomerised olefins.

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 linear alpha olefins and multiple carbon number isomerised olefins showed negative results. In vivo mouse micronucleus studies with linear alpha olefins and multiple carbon number isomerised olefins also produced no evidence of mutagenic effects. Based on the evidence presented above, dodecene 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.