Alkenes, C10-12, C11-rich

Endpoint summary

Description of key information

There are no acute oral, inhalation, or dermal toxicity studies on alkenes, C10-12, C11-rich.  Read-across studies from alkenes, C11-15 and hydrocarbons C14-30, olefin-rich (non-guideline and 16 CFR 15003, respectively) were identified for acute oral toxicity. In addition, a read-across studies from alkenes, C20-24 (OECD 420) and alkenes, C24-28 (OECD 401) were identified for acute oral toxicity.  Read-across studies from alkenes, C11-15 and hydrocarbons C14-30, olefin-rich were identified for acute dermal (non-guideline and OECD 402, respectively) toxicity. In addition, a read-across study from alkenes, C24-28 was identified for actue oral toxicity (OECD 401).  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 olefin), and hexadec-1-ene (OECD 403; linear alpha olefin) were used for acute inhalatory toxicity.
• The oral LD50 was > 10 mL/kg in female rats (i.e., > 7600 mg/kg) and 10 mL/kg (7600 mg/kg) in male rats for alkenes, C11-15.
• The oral LD50 was > 10,000 mg/kg in male and female rats for hydrocarbons C14-30, olefin-rich.
• The oral LD50 was > 2000 mg/kg in female rats for alkenes, C20-24.
• The oral LD50 was > 5000 mg/kg in male and female rats for alkenes, C24-28.
• 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 > 10,000 mg/kg in male and female rabbits for hydrocarbons C14-30, olefin-rich.
• 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

There are no acute oral, inhalation, or dermal toxicity studies on alkenes, C10-12, C11-rich; therefore, read-across was used withinisomerised olefins; alpha, internal, linear and branched – multiple carbon numbersfor 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, read across from alkenes, C11-15, hydrocarbons, C14-30, olefin-rich, alkenes, C20-24, and alkenes, C24-28 were used. For alkenes, C11-15, two groups of four male and four female, fasted, approximately 12 week old, Wistar rats were given a single oral dose of Internal Olefin 114 LP11 at doses of 5.0 and 10 mL/kg and observed for 9 days (Cassidy and Clark, 1977). 

 

No animals died at the 5.0 mL/kg dose level. Two male rats died at the 10 mL/kg dose level, no female rats died at this dose level. There were no treatment related clinical signs, necropsy data was provided. Animals that did not survive were reported to not eat or drink during the observation period, thus losing weight. The oral LD50 was estimated to be > 10 mL/kg in females (i. e., > 7600 mg/kg) and 10 mL/kg (7600 mg/kg) in males.

 

For hydrocarbons, C14-30, olefin-rich, five male and five female CFE rats were treated with a single oral dose of 10,000 mg/kg body weight of Ethyl Compound 100-606 via gastric intubation (Springer, 1977). Animals were then observed for mortality, body weight changes, and overt signs of toxicity for 14 days. At study termination all animals were sacrificed and necropsies were performed.

 

None of the 10 treated rats died during the 14-day observation period. Gross autopsy findings revealed blanched and mottled kidneys in almost all animals; however, body weight gain was normal. Based on the lack of mortality, the LD50was estimated to be > 10,000 mg/kg in both sexes. The test material was determined to be non-toxic when administered orally.

 

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, 2008a). 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.

For alkenes, C24-28, five male and five female rats were treated with 5000 mg/kg of the test material via gavage (Driscoll, 1998). The animals were observed for mortality or overt signs of toxicity 1, 2.5, and 4 hours after dosing and once daily thereafter for 14 days until study termination. At study termination, the animals were sacrificed and necropsies were performed.

 

None of the animals died during the course of the study. Clinical observations included hunched posture and pilo-erection in males. All animals exhibited normal body weight gain during the course of the study and no abnormalities were noted during necropsy. Based on these results, the authors concluded that the acute oral LD50 for C24-C30 alkenes, branched and linear, in arachis oil BP in Sprague- Dawley rats is >5000 mg/kg.

 

Based on these results, it can be inferred that alkenes, C10-12, C11-rich 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

To assess acute dermal toxicity, read across from alkenes, C11-15 and hydrocarbons, C14-30, olefin-rich was used. For alkenes, C11-15, groups of young Wistar rats, 4 male and 4 female, were dermally exposed to undiluted Internal Olefin 114 LP11 for 24 hours at doses of 1, 2, and 4 mL/kg bw (Cassidy and Clark, 1977). Animals then were observed for 9 days.

Three males died at the 4.0 mL/kg dose level. The rats that died were noted to not eat or drink thus losing a considerable amount of body weight. No other deaths were reported. The acute percutaneous LD50 of Internal Olefin 114 LP11 in rats was greater than 4 mL/kg (i.e., 3040 mg/kg) in females and between 2 and 4 mL/kg (i.e., 1520 to 3040 mg/kg) in males.

 

For hydrocarbons, C14-30, olefin-rich, three male and three female albino rabbits were treated dermally with a single application of 10,000 mg/kg Ethyl Compound 100-606. After application, the test chemical was held in contact with the skin by wrapping the treated areas with Saran wrap covered with a brown bag for 24 hours. Post treatment, the animals were observed for mortality and overt signs of toxicity for 14 days. On day 14, all surviving animals were sacrificed and necropsies were performed.

None of the six treated rabbits died during the 14 day observation period. Gross autopsy findings revealed no pathological changes in any rabbit and all six rabbits exhibited normal body weight gain. Based on the lack of mortality, the LD₅₀was estimated to be > 10,000 mg/kg in both sexes. The test material was determined to be non-toxic when administered dermally. 

 

Based on these results, it can be inferred that alkenes, C10-12, C11-rich 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 (Klimisch score = 2) 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) (Rinehart, 1967). 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. Given the lack of apparent significant toxicity among animals exposed to olefin vapours and mists (C6 to C16 in chain length) and the low vapour pressures of these substances, it is unlikely that multiple carbon number isomerised olefins, including alkenes, C10-12, C11-rich, 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. There are no kinematic viscosity data available for alkenes, C10-12, C11-rich; however read-across data was available for alkenes, C10 -13. The reported kinematic viscosity of alkenes, C10-13 at 40° C is 1.31 cSt (Da Col, 2009). Substances with kinematic viscosities less than 7 cSt or 20.5 cSt are classified for aspiration toxicity according to EU DSD and EU CLP regulations, respectively.  Based on the read-across strategy used for isomerised olefins, it is inferred that alkenes, C10-12, C11-rich are classified as Xn; R65, harmful: may cause lung damage if swallowed in accordance with Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway) in accordance with CLP EU Regulation 1272/2008. 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 significant 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, C10-12, C11-rich 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, C10-12, C11-rich are classified as Xn; R65, harmful (May cause lung damage if swallowed) in accordance with Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway) in accordance with CLP EU Regulation 1272/2008 based on the read-across viscosity value from a structural analogue, alkenes C10-13 at 40° C.