Ethylene polymerisation (triethylaluminium catalysed), distillation residue, C20-40 fraction

Endpoint summary

Description of key information

There are no acute inhalation or dermal toxicity studies on alkenes, C20-24.  One key oral acute toxicity study (OECD 420) was identified.  For acute dermal, a key study (non-guideline and OECD 402, respectively) was used.  Read-across data from alkenes, C10/C11/C12/C13 (OECD 403; isomerised olefins; alpha, internal, linear and branched – multiple carbon numbers), hex-1-ene (OECD 403; linear alpha olefins), and hexadec-1-ene (OECD 403; linear alpha olefins) were used for acute inhalatory toxicity.
• The oral LD50 was > 2000 mg/kg in female rats for alkenes, C20-24.
• The dermal LD50 was > 4 mL/kg (i.e., 3040 mg/kg) in female rabbits and between 2 and 4 mL/kg (i.e., 1520 to 3040 mg/kg) in male rabbits for alkenes, C11-15.
• The dermal LD50 was > 2000 mg/kg in male and female rabbits for alkenes, C20-24.
• The LC50 was > 2100 mg/m3 (2.1 mg/L) in rats for alkenes, C10/C11/C12/C13.
• The LC50 was 110,148 mg/m3 (110.1 mg/L) in male rats for hex-1-ene.
• The LC50 was ≥ 8500 mg/m3 (8.5 mg/L)in male rats for hexadec-1-ene.

Additional information

One key acute oral toxicity study was identified. There are no acute inhalation or dermal toxicity studies on alkenes, C20-24; therefore, read-across was used within multiple carbon number isomerised olefins for all acute endpoints. For acute inhalation toxicity, read across from linear alpha olefins also was used in order to build a weight-of-evidence case.

Acute Oral Toxicity

To assess acute oral toxicity for alkenes, C20-24, 5 fasted female Sprague-Dawley CD strain rats were given a single oral dose of ENORDET O241 at a dose of 2000 mg/kg bw and observed for 14 days (Sanders, 2008). There were no treatment related clinical signs, necropsy findings or changes in body weight. The oral LD50 was determined to be greater than 2000 mg/kg in females.

Based on these results, it is concluded that alkenes, C20-24 are 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

Two key studies were identified alkenes, C20-24. In the first study, groups of young adult Sprague-Dawley rats (5/sex) were dermally exposed to alkenes C20-24, branched and linear, undiluted for 24 hours to 35 cm²body surface at a limit dose of 2000 mg/kg bw (Driscoll, 1998b). There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 was determined to be > 2000 mg/kg in males and females.

 

In the second acute dermal toxicity study, groups of 10 (5 male and 5 female) Sprague-Dawley CD strain rats were dermally exposed to ENORDET O241 for 24 hours to 10% of body surface area (Sanders, 2008a). A single dose of 2000 mg/kg/bw was applied to the back and flanks of each animal and a semi-occlusive covering was placed over the treatment area. Animals were observed for 30 minutes, 1, 2, and 4 hours after dosing and once daily for 14 days.

 

There were no deaths, signs of systemic toxicity, dermal irritation, or abnormalities upon necroscopy. An increase in body weight was shown over the study period. The dermal LD50 was determined to be > 2000 mg/kg/bw in male and female rats.   

 

Based on these results, it can be inferred that alkenes, C19-23 are not acutely toxic by the dermal 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 Inhalation Toxicity

The overall dataset on the potential acute inhalation toxicity of isomerised olefins is limited. Three acute inhalation toxicity studies on 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 study with an isomerised olefin; alpha, internal, linear and branched – multiple carbon number, 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. 

 

In a series of read-across screening studies for linear alpha olefins 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 olefin substances, all the studies described above were considered in a weight-of-evidence approach to reach a robust conclusion on the acute inhalation potential of multiple carbon number isomerised olefin substances. Considering the lack of apparent significant toxicity among animals exposed to olefin vapours and mists (C6 to C16 in chain length), the physico-chemical properties of these substances (in particular the vapour pressure), multiple carbon number isomerised olefins are not considered 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, a 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. The reported kinematic viscosity value for alkenes, C20-24 measured at 40 °C is 5.466 mm²/sec (Intertek, 2010). This value meets the criteria for classification and labelling (< 7 or < 20.5 mm²/sec, respectively) for aspiration toxicity according to EU DSD/DPD 67/548/EEC and CLP Regulation 1272/2008 (GHS aligned). Therefore, alkenes, C20-24 are classified and labelled as Xn; R65: harmful, may cause lung damage if swallowed according to EU DSD/DPD 67/548/EEC and as Category 1 for aspiration toxicity; 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 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 toxicological differences between substances in multiple carbon number isomerised olefins and linear alpha olefins.  Therefore, read across between these two categories can be justified.

Justification for classification or non-classification

Based on evaluation of all the acute toxicity data discussed above, alkenes, C20-24 do not meet the criteria for classification as an acute oral, inhalation, or dermal toxicant under the EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008, because the LD50/LC50 values are greater than the limits for classification defined in the regulations.

Alkenes, C20-24 are classified and labelled as Xn; R65: harmful, may cause lung damage if swallowed according to EU DSD/DPD 67/548/EEC and as Category 1 for aspiration toxicity; H304: May be fatal if swallowed and enters airway according to EU CLP Regulation 1272/2008 (GHS aligned) based on its reported kinematic viscosity at 40 °C.