Dodecene

Endpoint summary

Description of key information

Read-across acute oral (OECD 420) and dermal (OECD 402) toxicity studies (OECD 420) were identified from octadecene (within category) and tetradecene (a structural analogue). Read-across data from alkenes, C10/C11/C12/C13 (OECD 403; an isomerised olefin; alpha, internal, linear and branched – multiple carbon numbers), hex-1-ene (OECD 403; linear alpha olefin), and hexadec-1-ene (OECD 403; linear alpha olefin) were used for acute inhalation toxicity.
• The oral LD50 was > 5050 mg/kg/bw in male and female rats for octadecene and tetradecene.
• The dermal LD50 was > 2020 mg/kg/bw in male and female rabbits for octadecene and tetradecene.
• The LC50 was 110,148 mg/m3 (110.1 mg/L) for male rats for hex-1-ene.
• The LC50 was = 8500 mg/m3 (8.5 mg/L) for male rats for hexadec-1-ene.
• The LC50 was > 2100 mg/m3 (2.1 mg/L) in rats for alkenes, C10/C11/C12/C13.

Additional information

Acute Oral Toxicity

There were no acute oral toxicity studies available for dodecene. However, there were two studies available on the acute oral toxicity of other isomerised olefins; alpha, internal, linear and branched - single carbon number. Read-across studies within category were selected from octadecene (within category; Kuhn, 1993), as well as a structural analogue, tetradecene (Kuhn, 1993). For the acute oral toxicity study on octadecene, five male and female young adult Sprague-Dawley rats were administered 5050 mg/kg (5.88 mL/kg) of octadecene via oral intubation. Body weight gain was unaffected. Toxicological and pharmacological signs were not noted. Notable observations included diarrhoea, piloerection, and polyuria. 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 acute oral LD50 for octadecene in Sprague Dawley rats is > 5050 mg/kg (5.88 mL/kg).

 

The acute oral toxicity study on tetradecene used the same procedure, in which five male and female young adult Sprague-Dawley albino rats were administered 5050 mg/kg (6.19 mL/kg) of tetradecene via oral intubation. Body weight gain was unaffected. Toxicological and pharmacological signs were not noted. Notable observations included decreased activity, diarrhoea, piloerection, and polyuria. These effects were no longer present by day 5 of the study period. 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 acute oral LD₅₀for tetradecene in Sprague Dawley rats is > 5050 mg/kg (6.19 mL/kg).

 

The results of these studies indicate that dodecene is not acutely toxic by the oral exposure route and since the available data do not meet the EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for this endpoint, a DNEL is not required.

Acute Dermal Toxicity

There were no acute dermal toxicity studies available for dodecene. However, there were two studies available on the acute dermal toxicity of isomerised olefins. Two key studies, one on octadecene (within category; Kuhn, 1993) and another on tetradecene (a strutural analogue; Kuhn, 1993), both considered to be of high quality, were used to potential assess the acute dermal toxicity of dodecene.

 

Octadecene was applied to the dorsal surface of the trunk (clipped free of hair) of five male and female New Zealand White rabbits. Body weight gain was affected by exposure to octadecene. Four males and females either lost weight or failed to gain weight between days 7 and 14. Toxicological and pharmacological signs were not noted. There were no signs of dermal irritation during the 14 day observation period. The only notable observation was slight diarrhoea in one female on days 9 and 10. Gross necropsy at study termination revealed no observable abnormalities. None of the treated animals died during the course of the study.

 

No mortality was observed in male or female rabbits dermally treated with 2020 mg/kg of tetradecene (Kuhn, 1993). Mean body weight and body weight gain appeared to be normal, except in one female who failed to gain weight between days 0 and 7. Slight polyuria was observed in one male rabbit from day 10 to day 14 of the observation period. No other signs of adverse toxicity related to treatment were observed and gross necroscopy at termination revealed no treatment-related findings.

Extrapolation of the results from these studies suggests that dodecene will not cause acute systemic toxicity following a single application to the skin. The available data does not meet the criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008) for this endpoint, thus a DNEL is not required. 

Acute Inhalation Toxicity

The overall dataset on the potential acute inhalation toxicity of single carbon number isomerised olefins is limited. Studies on the potential acute inhalation toxicity of linear alpha olefins and an isomerised olefin; alpha, internal, linear and branched – multiple carbon number were evaluated to build a weight of evidence for the assessment of this endpoint for single carbon number isomerised olefin substances. Individually, these studies were considered of limited usefulness due to inadequate reporting of the study methodologies and results; however the overall findings were useful when assessed collectively.

 

In a study on alkenes, C10/C11/C12/C13, 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. 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 (Blair and Sedgwick, 1980). 

In a series of screening studies conducted by Rinehart (1967), rats were exposed to either linear alpha olefin hex-1-ene vapour (for 4 hours) or linear alpha olefin 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 (Rinehart, 1967), 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.

Considering the limited amount of good quality information available on the acute inhalation toxicity of higher olefin substances, the aforementioned studies were collectively assessed using a weight-of-evidence approach to reach a robust conclusion on the acute inhalation potential for single carbon number isomerised olefins. The lack of apparent significant toxicity among animals exposed to olefin vapours and mists (C6 to C16 in chain length) and the physico-chemical properties of these substances (in particular the vapour pressure) indicate that single carbon number isomerised olefins, including dodecene, 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. There are no viscosity data available for dodecene.  However, read-across viscosity data was available for octadecene, a single carbon number isomerised olefin. The reported kinematic viscosity for octadecene was 3.44 mm²/sec at 40°C (Chilworth Technology LTD, 2010). The discriminating thresholds for classification for aspiration toxicity are 7 mm²/sec and 20.5 mm²/sec for EU DSD/DPD 67/548/EEC and CLP EU Regulation 1272/2008 (GHS aligned), respectively. Based on the read-across strategy used for isomerised olefins, it is inferred that dodecene be classified and labelled as R65: Harmful, may cause lung damage if swallowed, according to EU DSD/DPD 67/548/EEC and Category 1; H304: May be fatal if swallowed and enters airway according to EU CLP Regulation 1272/2008 (GHS aligned). A DNEL is neither feasible nor appropriate for this endpoint.

Justification for Read Across:

Several criteria justify the use of the read across approach to fill data gaps for single carbon number isomerised olefins using tetradecene as an analogue. Tetradecene is a single carbon number isomerised olefin; however, it is not a substance included under the Higher Olefins and Poly Alpha Olefins Consortium. However, tetradecene's chemical structure, physico-chemical properties, and mammalian health endpoints are comparable with other single carbon number isomerised olefins. Therefore, read across between tetradecene and single carbon number isomerised olefins can be justified.

 

Several criteria justify the use of the read across approach to fill data gaps for single 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 mildly irritating 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.

 

Several criteria justify the use of the read across approach to fill data gaps for single carbon number isomerised olefin substances using multiple carbon number isomerised olefin substance analogues. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter the effects on mammalian health endpoints. There is a consistent toxicity potency pattern for isomerised olefins with a range of carbon numbers and they are considered to have minimal acute toxicity potential. Genotoxicity studies indicate that these materials 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. The toxicological profile of multiple carbon number isomerised olefins described above indicates a low hazard potential for human health. Since multiple carbon number isomerised olefins, alkenes is comprised of a mixture of single carbon number isomerised olefins, no significant toxicological differences are expected between the two categories of substance and read across between these two categories can be justified.

Justification for classification or non-classification

Dodecene does not meet the criteria for classification as an acute oral, dermal, or inhalation toxicant under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 because the reported LD50/LC50 values for its structural analogues exceed the upper discriminating thresholds for classification as defined in the regulations.

Dodecene is classified as Xn; R65 harmful (May cause lung damage if swallowed) according to EU Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway) for CLP EU Regulation 1272/2008 (GHS aligned) based on the read-across kinematic viscosity of octadecene of 3.44 mm²/sec at 40°C.