Octacos-1-ene

Endpoint summary

Description of key information

Read-across acute oral toxicity studies from hexadec-1-ene (OECD 401; USEPA, TSCA) and C20-24 (OECD 423) were identified.  Read-across acute dermal toxicity studies from hex-1-ene (OECD 402), tetradecene, (OECD 402; a structural analogue), and alkenes, C20-24 (OECD  402; isomerised olefin; alpha, internal, linear and branched – multiple carbon numbers) were identified. Read-across acute inhalation studies from hexadec-1-ene (OECD 403), hex-1-ene (OECD 403) and alkenes, C10/C11/C12/C13 (OECD 403; multiple carbon number isomerised olefin) were identified.
• The oral LD50 for hexadec-1-ene was 10,000 mg/kg bw in male rats.
• The oral LD50 for C20-24 was > 5000 mg/kg bw in male and female rats.
• The dermal LD50 for hex-1-ene was >2000 mg/kg bw in male and female rabbits.
• The dermal LD50 for tetradecene was >2020 mg/kg bw in male and female rabbits.
• The dermal LD50 for alkenes, C20-24 was > 2000 mg/kg bw in male and female rabbits.
• The LC50 for hex-1-ene was 110,148 mg/m3 (110.1 mg/L) for male rats.
• The LC50 for hexadec-1-ene was ≥ 8500 mg/m3 (8.5 mg/L) for male rats.
• The LC50 for alkenes, C10/C11/C12/C13 was > 2100 mg/m3 (2.1 mg/L) in rats.

Additional information

Acute Oral Toxicity

No acute oral toxicity data exist for octacos-1-ene; therefore read-across studies were identified for this endpoint. In a read-across acute oral toxicity study from hexadec-1-ene (Myers et al., 1992), young, fasted Sprague-Dawley albino rats (10/sex/dose), were given a single oral dose of 5000 or 10,000 mg/kg Gulftene 16 (i.e., hexadec-1-ene) and observed for 14 days. There were no mortalities observed at the 5000 mg/kg bw dose; however 2/5 males and 2/5 females dosed with 10,000 mg/kg died. Necropsy revealed discoloration in lungs, intestines (with distention), liver (1 animal) and kidneys in rats that died or were sacrificed during the study period. Surviving animals had no remarkable gross lesions. No lesions were found in tissues taken to evaluate neurotoxicity (brains, spinal cords, sciatic nerves and pituitaries). The oral LD50 was reported as > 10,000 mg/kg bw in both male and female rats.

In another read-across acute oral toxicity study with C20-24 alpha olefins (Rausina, 1982), young, fasted Fischer 344 rats (5/sex) were given a single oral dose of Gulftene 24 (i.e., C20-24 linear alpha olefin) in corn oil at a dose of 5000 mg/kg bw and observed for 14 days. No treatment-related adverse effects were noted in body weight or necropsy observations and the only clinical signs noted (yellow staining of the inguinal region, oil around mouth, and brown staining on lower jaw) all disappeared by day 5 of the study period. The oral LD50 for Gulftene 20-24 was determined to be > 5000 mg/kg in male and female rats.

The results from these read-across studies indicate that structural analogues of octacos-1-ene (C16 and C20 -24 linear alpha olefins) are not acutely toxic by the oral route of exposure as all the reported LD50 values exceed the highest regulatory threshold for classification (2000 mg/kg bw). Therefore, octacos-1 -ene is not considered to be acutely toxic by the oral exposure route. It does not meet EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008) for this endpoint; hence an acute oral DNEL is not required.

 

Acute Dermal Toxicity

No acute dermal toxicity data exist for octacos-1-ene; therefore three read across studies with higher olefin substances were identified to assess this endpoint. In a study with linear alpha olefin, hex-1-ene, groups of New Zealand White rabbits (4/sex) were dermally exposed to undiluted Neodene 6 at a dose of 2000 mg/kg bw (Albert et al., 1983). All animals survived until end of study. There were no clinical signs of toxicity or effects on body weight. The skin was the only area affected with minimal irritation noted after the 24 -hour exposure period. By day 14, there was no evidence of irritation; however, at necropsy white crusty material on skin and fur, alopecia, and abrasions and focal reddened areas were noted in treated animals. Abrasions applied prior to treatment did not affect the results. The acute dermal LD50 for undiluted Neodene 6 alpha olefin was reported as >2000 mg/kg in rabbits.

 

In the second study, New Zealand White rabbits (5/sex) were dermally treated with tetradecene, a structural analogue, at a dose of 2020 mg/kg (2.47 mL/kg), undiluted for 24 hours (Kuhn, 1993). Other than one treated female that failed to gain weight between 0 to 7 days, there were no effects on body weight gain. There were no signs of dermal irritation during the 14 day observation period. The only notable observation was slight polyuria in one male between 10-14 days. Gross necropsy at study termination revealed no observable abnormalities. None of the treated animals died during the course of the study. Based on these results, the LD₅₀for tetradecene in albino rabbits was reported as > 2020 mg/kg.

The third study, involving a isomerised olefin; alpha, internal, linear and branched – multiple carbon numbers, was selected to show the span of the full carbon range and to provide sufficiently robust data for classification.In this study, groups of young adult Sprague-Dawley rats (5/sex) were dermally exposed to alkenes, C20-24, undiluted for 24 hours to 35 cm²body surface at a limit dose of 2000 mg/kg bw (Driscoll, 1998). Animals were then observed for 14 days. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 for alkenes, C20-24 was reported as > 2000 mg/kg in male and female rabbits.  

Based on the lack of apparent significant toxicity among animals dermally exposed to a C6 linear alpha olefin, a C13 single carbon number isomerised olefin, or a C20-24 multiple carbon number isomerised olefin and the read-across strategy used to evaluate this endpoint, octacos-1 -ene is not considered an acute dermal hazard. Since the available data do not meet the criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for this endpoint, an acute dermal DNEL is not required.

Acute Inhalation Toxicity

The overall dataset on the potential acute inhalation toxicity of linear alpha olefins is limited. Three potential acute inhalation toxicity of linear alpha olefin and multiple carbon number isomerised olefin substances were evaluated to build a weight of evidence for the assessment of this endpoint. Individually, these studies were considered of limited usefulness due to inadequate reporting of the study methodologies and results; however the overall findings are useful when assessed collectively (i. e. for building a weight-of-evidence). 

 

In a series of screening studies conducted by Rinehart (1967), rats were exposed to either hex-1-ene vapour (for 4 hours) or hexadec-1-ene saturated mist (for 1 hour). The study on hex-1-ene was well conducted and reported, although high exposure concentrations were used (above the 20 mg/L limit for vapours required for classification and labelling; EU CLP). No mortality was reported in the lowest dose group (95 mg/L) although mild signs of anaesthesia were noted among treated animals. 

In the study on hexadec-1-ene, groups of male Wistar rats (number of animals not specified) were exposed for 1 hour to hexadec-1-ene at an estimated aerosol mist concentration of 8500 mg/m³(particle size less than< 8.0 microns). Rats appeared drowsy on removal from the chamber and the fur of all animals tested was oily due to deposition of the substance. No mortality, significant changes in body weight or gross pathological changes post autopsy were observed at the end of the 14-day observation period. Since this study was conducted for screening purposes, full details of the methods and results were not presented and the findings are thus considered of limited usefulness.  

In a read-across study to an isomerised olefin; alpha, internal, linear and branched – multiple carbon numbers, rats (numbers not reported) treated with 2.1 mg/L alkenes, C10/C11/C12/C13 vapour (equivalent to 2100 mg/m³) for 4 hours, lachrymated and salivated during exposure (Blair and Sedgwick, 1980). No other toxic signs were reported during exposure or during the 14 day observation period. No gross pathology or histopathology was conducted and although body weights were taken, the results were not presented. 

Considering the limited amount of good quality information available on the acute inhalation toxicity of linear alpha olefins, the aforementioned acute inhalation studies were collectively assessed using a weight-of-evidence approach to reach a robust conclusion on the acute inhalation potential for this group of substances. The lack of apparent significant toxicity among animals exposed to olefin vapours and mists (C6 to C16 in chain length) and the low vapour pressure for these substances indicate that linear alpha olefins, including octacos-1-ene, are unlikely to represent an acute inhalation hazard. Since the available data do not meet the criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for this endpoint, an acute inhalation DNEL is not required.

Aspiration Toxicity

Regulatory classification and labeling for aspiration toxicity relies on the measured or calculated kinematic viscosity of a substance at 40°C rather than results from toxicological studies with animals. All linear alpha olefins which exist as liquids at 40°C are classified as aspiration hazards because their respective kinematic viscosities are below the discriminating thresholds established for classification and labelling set forth in EU DSD/DPD 67/548/EEC (< 7 mm²/sec) or CLP EU Regulation 1272/2008 (GHS aligned)(< 20.5 mm²/sec). There are no kinematic viscosity data available for octacos-1-ene. Octacos-1-ene exists as a solid substance at room temperature and is expected to have a melting point > 38 °C based on read across to docos-1-ene (Lide, 2008). The physicochemical properties of this substance preclude it from being considered as a potential aspiration toxicant. A DNEL is neither feasible nor appropriate for this endpoint.

Justification for Read Across from Tetradecene

Several criteria justify the use of the read across approach to fill data gaps for linear alpha olefin substances using tetradecene. Tetradecene is a single carbon number isomerised olefin.  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. Like other single carbon number isomerised olefins, tetradecene is not acutely toxic via oral or dermal routes of exposure in animal studies and is therefore considered to have minimal acute toxicity potential. Other studies on single carbon number isomerised olefins (i.e., a 42-53 day reproduction/developmental toxicity screening study with octadecene) showed no adverse effects on the F0 or F1 generation at the highest dose tested in rats. The toxicological profile for single 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 tetradecene and linear alpha olefins. Therefore, read across between tetradecene and linear alpha olefins is justified.

Justification for Read Acrossfrom Multiple Number Isomerised Olefins

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

Based on evaluation of all the acute toxicity data discussed above, octacos-1-ene does not meet the criteria for classification as an acute oral, inhalation or dermal toxicant under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 because the LD50/LC50 values reported for structural analogues of this substance are greater than the discriminating threshold limits for classification defined in the regulations.

Octacos-1-ene is not classified as an aspiration toxicant because it exists as a solid substance at 40 ° C.