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Toxicological information

Neurotoxicity

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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.

Key value for chemical safety assessment

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 for linear alpha olefin substances using multiple carbon number isomerised olefin analogues.  Studies indicate that changing the carbon number, the location of the double bond, or adding branching to olefins does not measurably alter their respective toxicological effects on mammalian health endpoints. Multiple carbon number isomerised olefins are considered to have minimal acute toxicity potential. Genotoxicity studies indicate that these substances 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, a multiple carbon number isomerised olefin. The toxicological profile for multiple carbon number isomerised olefins, outlined above, indicates a low hazard potential for human health. There do not appear to be any significant toxicological differences between multiple carbon number isomerised olefins and linear alpha olefins. Therefore, read across between these two categories is 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 alkenes, C11/C13/C14 are neurotoxic. Therefore, alkenes, C11/C13/C14 do not meet the criteria for classification and labelling as described in Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.