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Description of key information

One key acute oral toxicity study (OECD 420) and one acute dermal (OECD 402) was identified.  Several other key acute oral toxicity studies (16 CFR 1500; OECD 401; OECD 420; OECD 423) and key acute dermal toxicity studies (OECD 402) were identified for poly alpha olefins or structural analogues that showed similar results. Eight key acute inhalation studies (OECD 403) were identified for poly alpha olefins.
• The oral LD50 was > 5000 mg/kg bw in male and female rats for dec-1-ene, dimers, hydrogenated; 1-dodecene dimer with 1-decene, hydrogenated; 1-decene trimer, hydrogenated and tetramers; 1-decene, homopolymer, hydrogenated; Alkane 4; and Alkane 5.
• The oral LD50 was > 2000 mg/kg bw in male and female rats for decene trimer hydrogenated.
• The dermal LD50 was > 3000 mg/kg/bw in male and female rabbits for dec-1-ene, dimers, hydrogenated.
• The dermal LD50 was > 2000 mg/kg/bw in male and female rats for both 1-dodecene dimer with 1-decene, hydrogenated; 1-dodecene dimer with 1-decene, hydrogenated; Alkane 4; and Alkane 5.
• 1-Dodecene dimer with 1-decene, hydrogenated (read across to dec-1-ene, dimers, hydrogenated; kinematic viscosity = 5.1 cSt, C-20) is classified as an acute inhalation toxicant based on a weight of evidence analysis relying on viscosity, carbon number, and reported LC50 values for poly alpha olefins.
• 1-Dodecene dimer with 1-decene, hydrogenated is classified as an aspiration hazard based on read-across viscosity datat for dec-1-ene, dimers, hydrogenated.

Key value for chemical safety assessment

Additional information

Acute Oral Toxicity

There are several studies available on the acute oral toxicity of poly alpha olefins. One key study (Dougherty, 1989) was identified from 1-dodecene dimer with 1-decene, hydrogenated. In this study, groups of fasted, young adult Sprague-Dawley Bkl:(SD) rats, five per sex, were given a single oral dose of undiluted Oronite XS 101 at a dose of 5000 mg/kg bw and observed for 14 days. Five rats per sex were left untreated as controls.

No mortality occurred throughout the study. Mean body weight determinations did not reveal any significant differences between animals in the treatment group and their concurrent controls. No signs of adverse clinical toxicity were observed in either male or female rats in the treatment group. However one female rat in the control group had reduced food intake and faeces on day 13 of the observation period due to lack of food. Necropsy on day 14 revealed multifocal chronic interstitial pneumonia in one treated female. This is not considered to be related to treatment. The oral LD50 was determined to be greater than 5000 mg/kg in both male and female rats.

Additionally, key studies showing similar results were identified for the following substances: Alkane 4 (i.e., 1-dodecene trimer, hydrogenated, a structural analogue); dec-1-ene, dimers, hydrogenated; 1 -decene trimer, hydrogenated and tetramers; Alkane 5 ( i.e., 1-decene 1-dodecene homopolymer, a structural analogue); 1 -decene, homopolymer, hydrogenated; and decene trimer hydrogenated. LD50 values for these substances were as follows:

The oral LD50 was > 5000 mg/kg bw in male and female rats for Alkane 4; dec-1-ene, dimers, hydrogenated; 1 -decene trimer, hydrogenated and tetramers; Alkane 5; and 1-decene, homopolymer, hydrogenated.

The oral LD50 was > 2000 mg/kg bw in male and female rats for decene trimer hydrogenated

The results of these studies indicate that poly alpha olefins 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

There are several studies available on the acute dermal toxicity of poly alpha olefins. One key study (Dougherty, 1989) was identified for 1 -dodecene dimer with 1 -decene, hydrogenated. In the identified study, five young adult Sprague-Dawley males and females were dermally exposed to undiluted Oronite XS 101 for 24 hours at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days (Dougherty, 1989).

 

No mortality was observed. Mean body weight data indicates no significant difference between treated animals and their concurrent controls. Skin irritation was noted in controls and treated animals, but the irritation was more severe and persistent in the treated animals with cracking and scarring occurring in the treated animals. No other clinical signs of toxicity related to treatment were observed through the 14-day observation period. Necropsy at the end of the 14-day observation period revealed a dilated pelvis in the kidney of 1 male rat treated at 2000 mg/kg, but is not considered to be a treatment-related. The dermal LD50 was determined to be greater than 2000 mg/kg in male and female rats.

There also are several studies available on the acute dermal toxicity of poly alpha olefins and structural analogues that showed similar results. Key studies were identified for the following substances: dec-1-ene, dimers, hydrogenated; Alkane 4 (a structural analogue); and Alkane 5 (a structural analogue). Summaries of these studies are presented below. 

 

One key study (Paa and Mastri, 1974) was identified for dec-1-ene, dimers, hydrogenated. In the identified study, two male and female New-Zealand rabbits were clipped free of hair on the back and 3000 mg/kg of the test material (Synfluid, Sample SF001-3) was applied to the exposed skin uniformly. The test material was covered with occlusive dressing for 24 hours. Following the 24 hour observation period, the occlusive dressing was removed and any remaining test material was removed. Animals were observed for mortality, local skin irritation, and behavioural abnormalities until day 14 of study. Individual body weights were recorded prior to test chemical application and on days 7 and 14. All animals were sacrificed on day 14 and received a full necropsy.

 

One female rabbit died prematurely, on day 9 of the observation period, and adverse body-weight changes (emaciation) were noted in this animal prior to death. No other clinical, behavioural or systemic responses were noted in the animals. Necropsies did not reveal any treatment-related gross pathologic alterations. Skin reactions included pale red erythema and slight to mild oedema at the 24 hour observation period. These reactions had reduced notably by day 14 to slight oedema and desquamation. No other signs of toxicity were noted. Based on these results, the dermal LD50of Synfluid, Sample SF001-3 was estimated to be > 3,000 mg/kg in rabbits indicating that the test material was practically nontoxic when applied undiluted to the skin of rabbits.

 

For the Alkane 4 study, young adult Sprague-Dawley rats (5/sex) were dermally exposed to Alkane 4 (undiluted) for 24 hours to 37 cm2of clipped skin surface at a single dose of 2000 mg/kg bw (Driscoll, 1995). Animals then were observed for 14 days. There were no clinical signs of toxicity or signs of skin irritation. Body weight appeared to be unaffected by treatment. No gross abnormalities were noted at necropsy. The acute dermal LD50 for Alkane 4 was greater than 2000 mg/kg.

 

One read-across study was identified from Alkane 5, a structual analogue. In this study, five male and female Sprague-Dawley rats were clipped free of hair on the back and flanks and 2000 mg/mL of Alkane-5 was applied to the exposed skin (Driscoll, 1995). Following treatment, animals were observed for overt signs of toxicity at 1, 2.5, and 4 hours after dosing and daily there after until study termination on day 14. None of treated animals died during the course of the study. No signs of systemic toxicity, skin irritation or abnormalities were noted during the observation periods or necropsy. Based on these observations, the acute dermal median lethal dose (LD50) of Alkane 5 in the Sprague-Dawley rat was reported to be greater than 2000 mg/kg bodyweight.

 

The results of these studies indicate that poly alpha olefins 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

  Eight key acute inhalation studies were identified for poly alpha olefins. Four studies were identified for dec-1-ene dimers, hydrogenated and one study was identified for each of the following: C8/C10/C12-based PAO2, 1-decene, homopolymer, hydrogenated, Alkane 4 (a structural analogueof 1-decene trimer, hydrogenated and tetramers), and 1-dodecene polymer with 1-decene, hydrogenated.

 

The acute inhalation toxicity of C8/C10/C12-based PAO2 (C16, kinematic viscosity at 40 °C based on read across to dec-1-ene dimers, hydrogenated, assigned value of 5.1 cSt) was investigated in a GLP-compliant near-guideline study using groups of rats (5/sex) exposed nose-only to respirable aerosol (MMAD 3.1 um) of Alkane 1 at concentrations of 1.05 or 2.09 mg/L for 4-hours (Douds, 1998). The animals were observed up until the time of death or day 14 post-exposure, which ever occurred sooner. Nine of 10 animals exposed to 2.09 mg/L and 4/10 exposed to 1.05 mg/L died on study day 2, with dark red lungs recorded in decedents at necropsy. The LC50 from this study was therefore <2.09 mg/L.

 

In the first study for dec-1-ene dimers, hydrogenated (C20, kinematic viscosity at 40 °C = 5.1 cSt), rats (5 males/5 females) were exposed whole-body to a respirable aerosol (MMAD around 1 um) of MCP-992 at 4.80 mg/L for 4-hours followed by observation for up to 14 days (Whitman, 2002). The investigation followed OECD guideline 403. Seven of ten animals were found dead between day 0 and day 2, with dark red discoloured lungs noted at necropsy in decedent animals as well as in two of the three survivors. The reported LC50 from this study was <4.80 mg/L.

 

In the second study on dec-1-ene dimers, hydrogenated, groups of rats (10/sex) were exposed whole-body to respirable aerosol concentrations of SHF-21 at 0.46 mg/L (MMAD = 1.99 um) or 1.81 mg/L (MMAD = 1.30 um) for 4-hours, with one half of the animals scheduled for necropsy on study day 2 and the remainder on study day 14 (Pulkowski, 1995). In all other respects the study design appeared near-guideline. Animals exposed to 1.81 mg/L exhibited breathing difficulties (rates) on study day 2, with one female found dead that morning. Animals exposed to 0.46 mg/L exhibited no clinical signs and survived to scheduled necropsy. Macroscopic examination of the lungs from both exposure groups revealed dark red focal lesions of the lungs in the vast majority of animals, which had resolved by day 14. The LC50 from this study was >1.81 mg/L.

 

In the remaining investigations for dec-1-ene dimers, hydrogenated, rats (5/sex) were exposed whole body to either to a graded series of aerosol concentrations of SF-0203-41 (0, 0.76, 0.93, 1.10, 1.40 or 5.10 mg/L; MMAD 2.9 um for 4-hours (Ulrich, 1982) or a single level of synfluid PAO 2cSt (5.17 mg/L; MMAD 1.9 um) for 1-hour followed by necropsy of survivors in both instances (Salame, 1994). The studies were OECD guideline 403 compliant. An acute 4-hour LC50 of 1.17 mg/L was reported for SF-0203-41, with dose-dependent mortality occurring in all groups within 2-3 days of exposure (no survivors in the high dose group). In-life clinical signs included dyspnoea, with red or dark red lung foci observed macroscopically in decedent animals. Pulmonary congestion, pulmonary oedema and intra-alveolar haemorrhage were detected microscopically in animals exposed to 5.10 mg/L for 4-hours. In the 1-hour exposure study with synfluid PAO 2cSt, 9/10 animals were found dead on study days 1-3, preceded by respiratory distress. The LC50 for this latter investigation was <5.15 mg/L.

 

The acute inhalation toxicity of Alkane 4 (a structural analogue most similar to 1-decene trimer, hydrogenated and trimers, C30-40, kinematic viscosity at 40 °C = 15-20 cSt) was measured in a GLP-compliant OECD guideline 403 study using groups of rats (5/sex) exposed nose-only to a respirable aerosol (MMAD 1.2 um) of 5.06mg/L for 4-hours (Blagden, 1995). No mortalities were reported. Clinical signs, observed after removal from the exposure chamber included wet fur, hunched posture and pilo-erection, increased respiration rate, ptosis, and isolated incidents of decreased respiration rate and red/brown stain on the head. All animals had recovered and appeared to be normal by day 2. No gross abnormalities were reported at necropsy. The reported LC50 for Alkane 4 was >5.06 mg/L.

 

The acute inhalation toxicity of 1-decene, homopolymer, hydrogenated (C30, kinematic viscosity at 40 °C = 16.9-60 cSt) was investigated in a GLP-compliant OECD guideline 403 study using groups of rats (5/sex) exposed nose-only to a respirable aerosol (MMAD 2.1 um) of 5.2 mg/L of MRD-05-465 for 4-hours (Hoffman, 2006). No clinical signs of note were recorded post-exposure, and all animals survived to study day 15 with no abnormalities detected at gross necropsy. The LC50 for this sample was >5.2 mg/L.

 

The acute inhalation toxicity of Alkane 5 (a structural analogue most similar to 1-dodecene polymer with 1-decene hydrogenated; C30-48, kinematic viscosity at 40 °C based on read-across to 1-dodecene homopolymer hydrogenated (consisting of 50 wt% or more of species of the same molecular weight), assigned value of 25.3-44.3 cSt) measured in a GLP-compliant OECD guideline 403 study using groups of rats (5 /sex) exposed nose-only to a respirable aerosol (MMAD 1.3 um) of 5 mg/L for 4-hours (Blagden, 1995). No mortalities were reported. Clinical observations, including wet fur, hunched posture, pilo-erection, both decreased and increased respiratory rates, ptosis and red/brown staining around the eyes, were all resolved 2 or 3 days post-exposure.  Necropsy results reported one male exhibiting dark patches on the lungs. No other abnormalities were reported from necropsy. The reported LC50 for Alkane 5 was >5.0 mg/L.

 

The available experimental data demonstrate that respirable aerosols of C8/C10/C12-based PAO2 (results available on one sample) and dec-1-ene dimers, hydrogenated (results available on 4 samples) are hazardous following acute inhalation exposure, with 4-hour LC50 values consistently below 5 mg/L. Physico-chemical characteristics of the substances giving these results reveals that they possess an average carbon number of C16 (C8/C10/C12-based PAO2) to C20 (dec-1-ene dimers, hydrogenated) and a viscosity of less than 15 cSt at 40 °C . In contrast, LC50 information for 1-decene, homopolymer, hydrogenated, 1-decene trimer, hydrogenated and tetramers, and 1-dodecene polymer with 1-decene hydrogenated demonstrates that they are not harmful after acute inhalation exposure to aerosol, with physicochemical properties which indicate a kinematic viscosity exceeding 15 cSt at 40 °C and an average C-number 30 or higher.

 

For poly alpha olefins where no experimentally derived LC50 value is available, the weight of evidence analysis therefore supports classification for acute inhalation toxicity (R20) when the kinematic viscosity is less than 15 cSt and the primary carbon number is 30 or less.

 

Where experimental data are available, classification will be results-based.

Based on the weight of evidence analysis described above, 1-dodecene dimer with 1-decene, hydrogenated (read across to dec-1-ene, dimers, hydrogenated; kinematic viscosity = 5.1 cSt, C-20) meets the criteria for classification and labelling this substance as R20 (Harmful by inhalation) as defined by EU Dangerous Substance Directive 67/548/EEC (R20) and as a Category 4 inhalation hazard, H332 in accordance with CLP Regulation 1272/2008 (GHS aligned).

 

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 1-dodecene dimer with 1-decene, hydrogenated. Therefore, read across was made to dec-1-ene, dimers, hydrogenated. The reported kinematic viscosity value for dec-1-ene dimers, hydrogenated at 40 °C is 5.1 cSt (Chevron Phillips Chemical Company, 2002). This value meets the criteria for classification for aspiration toxicity under DSD (< 7 cSt) and CLP regulations (< 20.5 cSt). Based on the read-across strategy used for poly alpha olefins, it is therefore inferred that 1-dodecene, dimer with 1-decene, hydrogenated is classified as Xn; R65 harmful (May cause lung damage if swallowed) under EU Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway).

 

Justification for Read Across

 

Several criteria justify the use of the read across approach to fill data gaps for poly alpha olefins using Alkane 4, Alkane 5, and 1-octene dimer, hydrogenated as an analogue. Alkane 4, Alkane 5, and 1-octene dimer, hydrogenated like other compounds in this category, are poly alpha olefins, i. e., highly branched isoparaffinic chemicals produced by oligomerization of oct-1-ene, dec-1-ene, and/or dodec-1-ene. Therefore, their physiochemical and toxicological properties are expected to be similar to those of other poly alpha olefins.

Justification for classification or non-classification

Based on evaluation of the acute oral and dermal toxicity data discussed above, 1-dodecene dimer with 1-decene, hydrogenated does not meet the criteria for classification as an acute oral or dermal toxicant under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 because the reported LD50 values for its structural analogues exceed the limits for classification defined in the regulations.

 

Based on the weight of evidence analysis of the acute inhalation toxicity studies discussed above, 1-dodecene dimer with 1-decene, hydrogenated meets the criteria for classification and labelling as an acute inhalation toxicant under EU Dangerous Substances Directive 67/548/EEC and CLP EU Regulation 1272/2008. 1 -Dodecene dimer with 1-decene, hydrogenated is classified as Xn, R20: Harmful by inhalation under EU Dangerous Substances Directive 67/548/EEC and as a Category 4 acute inhalation toxicant; H332: Harmful if inhaled, under CLP EU Regulation 1272/2008.

1 -Dodecene dimer with 1-decene, hydrogenated is classified as Xn; R65 harmful (May cause lung damage if swallowed) in accordance with EU 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 (GHS aligned) based on the read-across kinematic viscosity for dec-1–ene, dimers, hydrogenated of 5.1 cSt at 40° C.