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Description of key information

Key value for chemical safety assessment

Additional information

There was one key toxicokinetic study identified which evaluated the absorption and distribution of linear alpha olefins, oct-1-ene, non-1-ene, and dec-1-ene, and the corresponding C8, C9, and C10 isoalkanes in rats (Zahlsen, 1993). Male Sprague-Dawley rats (16/dose) were exposed via whole body inhalation to 100 ppm vapour of the individual test substances for 12 hours/day for 3 consecutive days. Concentrations of the hydrocarbons were measured in blood, brain, liver, kidney and perirenal fat immediately following each 12 hour exposure and 12 hours following the last exposure. Higher concentrations of linear alpha olefins were measured in each of the respective organs compared with measured concentrations of the corresponding isoalkanes, with the highest concentrations measured in fat. All measured concentrations of linear alpha olefins and isoalkenes were significantly decreased following the 12 hour recovery period; however the largest residual accumulations were measured in the fat. With the exception of the kidney, accumulation of the respective test substances in all organs was shown to increase with increasing carbon number. 

 

There were two supporting studies available which identified metabolic pathways of linear alpha olefins. In an in vitro toxicokinetic study designed to determine if carbon-carbon double bonds are metabolized to glycols via direct dihydroxylation of the olefinic bond or via epoxide intermediates, complete metabolic conversion of oct-1-ene to glycolic products was accomplished using an NADPH generating system and rat liver microsomes (Maynert et al., 1969). When competitive inhibitors of epoxide hydrolase were used in the experiment, both epoxides and glycols were formed. In the absence of the inhibitor, only glycols were formed confirming that the metabolism of olefins proceeds via epoxide intermediates.

 

In the second study, two metabolic pathways for oct-1-ene are described (White et al., 1986). Oct-1-ene was converted to octane-1,2-oxide which was rapidly hydrolyzed to octane-1,2-diol using an in vitro NADPH generating system (pathway 1). An alternative metabolic route was described in which oct-1-ene was converted to a reactive intermediate, octen-3-one, which formed S-3-oxo-octyl-acetylcysteine in in vitro systems using NADPH, cytochrome P450, NAD(P), and N-acetylcysteine (pathway 2). Metabolism of oct-1-ene via pathway 1 was significantly more rapid (40 times) that metabolism via pathway 2.

 

There were no studies identified which assessed or described the excretion profile for linear alpha olefins or single or multiple carbon number isomerised olefins.

Justification for Read Across:

Several criteria justify the use of the read across approach to fill data gaps for multiple 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 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 inmultiple carbon number isomerised olefins and linear alpha olefins.  Therefore, read across between these two categories can be justified.