Dodecene

Neurotoxicity

Description of key information

Seven studies were identified that examined neurotoxicity endpoints.  These studies were comprised of three 28-day oral toxicity studies (hex-1-ene; alkenes, C16-18; and alkenes, C20-24), a 90-day oral toxicity study (alkenes, C20-24), a 90-day inhalation toxicity study (hex-1-ene), two reproductive/developmental screening studies (tetradec-1-ene and alkenes, C6).  The overall weight of evidence from these seven studies indicates that higher olefins are not associated with neurotoxic effects following repeated dosing; therefore classification and labelling is not required for this endpoint.

Additional information

Potential neurotoxic effects of higher olefins were evaluated in seven repeated dose studies, each of which contained a neurotoxicity screening component. Potential neurotoxicity of repeated exposure to linear alpha olefins was assessed in three studies: a four week oral repeated dose study with hex-1-ene (Dotti, 1994); a 42-51 day combined repeated dose/reproductive/developmental study with tetradec-1-ene (Daniel, 1994), and a 90-day inhalation repeated dose study with hex-1-ene (Bennick, 1984). No treatment-related effects related to neurotoxicity were reported in any of these studies. No adverse effects on measured neurotoxic parameters were reported in a combined repeated dose/ reproductive/developmental study for isomerised olefins; alpha, internal, linear and branched – multiple carbon numbers, alkenes, C6, (Thorsud, 2003). Additionally, no treatment-related neurotoxic effects were observed in a four week oral repeated dose study with multiple carbon number isomerised olefin, alkenes, C16 -18 (Amodrill 1000, Clubb, 2000) using functional observation battery tests (FOBs) or a 90-day oral repeated dose study with 4 week recovery with multiple carbon number isomerised olefin, alkenes, C20 -24 (Brooker, 1999). Similar results were observed in a 28 -day oral repeated dose study conducted with C20 -24, in which there were no treatment-related changes to behaviour functional performance or sensory reactivity in rats (Dunster, 2008). The overall weight of evidence from these seven studies indicates that higher olefins are not associated with neurotoxic effects following repeated dosing; therefore classification and labelling is not required for this endpoint.

Justification for Read Across:

Several criteria justify the use of the read across approach to fill data gaps forisomerised olefins; alpha, internal, linear and branched – single carbon numbersubstances 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 linear alpha olefins supported by a low toxicity concern for acute oral, dermal and inhalation exposure. These materials are slightly irritating to skin and slightly 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 signficant 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 forisomerised olefins; alpha, internal, linear and branched – single carbon numbersubstances 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 linear alpha olefins supported by a low toxicity concern for acute oral, dermal and inhalation exposure. These materials are slightly irritating to skin and slightly 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.

Justification for classification or non-classification

All studies identified that evaluated neurotoxicity endpoints from linear alpha olefins and multiple carbon number isomerised olefins showed negative results for neurotoxicity. Based on the information provided, it is unlikely that dodecene is neurotoxic. Therefore, dodecene does not meet the criteria for classification and labelling as described in Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.