Dodec-1-ene

Neurotoxicity

Description of key information

Neurotoxicity evaluations have been conducted for six members of this category covering C6 to C20-24. The majority of these investigations involved sub-acute oral (gavage) administration to rats, supported by two sub-chronic studies conducted using the oral or inhalation route. After oral exposure, the NOAEL for neurotoxicity was 1,000 mg/kg/day (the highest dose tested). After inhalation, a NOAEC of 3,000 ppm (10,326 mg/m3; the highest concentration tested) was obtained. 

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Effect on neurotoxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Effect on neurotoxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Information is available on the Neurotoxicity potential of the following members of this category:

Test substance identity	Neurotoxicity
Hex-1-ene	v
Alkenes, C6	v
Tetradec-1-ene	v
Alkenes, C16-18	v
Alkenes, C20-24	v
Alkenes, C20-24, branched and linear	v

Details of these studies are summarised below.

Information is available from two studies that investigated the neurotoxicity potential of 1-hexene after oral and inhalation exposure.

In a sub-acute investigation (Dotti et al., 1994), 1-hexene was administered by oral gavage to 5 Wistar rats/sex/dose at dose levels 0, 10, 101, 1010, or 3365 mg/kg bw/day for 28 consecutive days. Neurobehavioural examinations (rotorod test) conducted on study days 1, 2, 4, 14, 21 and 28 revealed no effects on muscle coordination The NOAEL for neurotoxicity was therefore 3365 mg/kg bw/d.

 In a sub-chronic investigation (Bennick et al., 1994), 1-hexene (Neodene 6 alpha olefin) was administered to Fischer 344 rats/sex/concentration by dynamic whole body exposure at concentrations of 0, 300, 1000, or 3000 parts per million (corresponding to 0; 1033; 3442; or 10,326 mg/m3) for 6 hours a day, 5 days a week, for 13 weeks. Neuromuscular testing and neurohistopathological investigations revealed no treatment-related changes, and the NOAEC for neurotoxicity was 3000 parts per million (10,326 mg/m3).

Information is available from one study that investigated the neurotoxicity potential of Alkenes, C6.

In a short-term repeat dose toxicity study (Thorsud, 2003), C6 Alkenes dissolved in corn oil were administered via oral gavage to male and female Sprague-Dawley rats (12/sex/dose) at dose levels of 100, 500 and 1000 mg/kg/day for 34 (males) or 38 (females) days.  The animals were assessed for a number of neurological endpoints, including an abbreviated functional observational battery test (conducted weekly) and a full functional observational battery test on day 28. Motor activity was also measured. The NOAEL for neurotoxicity in this study was 1000 mg/kg/day.

Information is available from one study that investigated the neurotoxicity potential of 1-tetradecene.

In this study, (Daniel, 1995), eight Sprague-Dawley rats/sex/dose were administered 1-tetradecene at doses of 0, 100, 500, or 1000 mg/kg/day for 43 to 47 days. Neurotoxicity assessment included a functional observational battery (FOB) and motor activity tests. No treatment-related changes were apparent, with a NOAEL of 1000 mg/kg/day.

Information is available from one study that has investigated the neurotoxicity potential of Alkenes, C16-18.

In this study (Clubb, 2000), rats were administered Alkenes, C16-18 (AmoDrill 1000) via gavage at doses of 0, 25, 150, or 1000 mg/kg/day in corn oil for 28 days.  The test conditions complied with OECD 424 guidelines and the statistical methods used were appropriate, with the animals assessed for endpoints including mortality, clinical signs and functional observation battery tests (the latter including sensory activity, grip strength, motor activity and landing foot splay). Sporadic significant were noted in the FOB data however these were not considered treatment related. Due to a lack of any definitive adverse effects, the NOAEL for neurotoxicity in this study is 1000 mg/kg/day.

Information is available from one study that investigated the neurotoxicity potential of Alkenes, C20-24.

In this study (Dunster et al., 2008), Alkenes, C20-24 were administered by oral gavage to 40 male and female Sprague-Dawley rats at dose levels of 0, 30, 300, and 1000 mg/kg/day for 28 days. Neurobehavioural observations (functional performance, sensory reactivity, behavior) were recorded on days 4, 11, 18, and 25. There were no toxicologically significant differences between treated and control animals, and the NOAEL for neurotoxicity was 1000 mg/kg/day.

Information is available from one study that investigated the neurotoxicity potential of Alkenes, C20-24, branched and linear.

In this investigation (Booker, 1999), C20-C24 Alkenes, branched and linear, was administered via oral gavage to male and female Crl:CD BR rats (10 per sex per dose) at doses of 0, 100, 500, or 1000 mg/kg/day for a period of 13 weeks. An additional 10 rats per sex per group for control and high-dose groups were observed through a subsequent 4-week recovery period.  A neurobehavioral screen was (including motor activity, manipulation, sensory activity, grip strength) was included in the study design with testing conducted on the main and recovery group animals. No obvious treatment related differences were apparent relative to the controls. Based on these findings, a NOAEL of 1000 mg/kg/day was established for neurotoxicity in this 90-day oral toxicity study.

Justification for selection of effect on neurotoxicity via oral route endpoint:
Neurotoxicity evaluations via the oral route have been conducted for six members of this category covering C6 to C20-24. The majority of these investigations involved sub-acute oral (gavage) administration to rats, supported by a sub-chronic oral study. The NOAEL for neurotoxicity was 1000 mg/kg/day (the highest dose tested).

Justification for selection of effect on neurotoxicity via inhalation route endpoint:
Neurotoxicity evaluations after inhalation have been conduced on Alkenes, C20-24, branched and linear. A NOAEC of 3,000 ppm (10,326 mg/m3), the highest concentration tested, was obtained.

Justification for classification or non-classification

Neurological assessments have been conducted on 6 members of this category covering C6 to C20 -24. The majority of these investigations have used oral (gavage) exposure with one study involving treatment via inhalation.There was no evidence of neurotxicity in any of these studies, and no classification is necessary according to the CLP regulation.