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Description of key information

Several 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. Eight key acute inhalation studies (OECD 403) were identified for poly alpha olefins and used to build a weight of evidence case.
• 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-Tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt).) (kinematic viscosity = 39.57 cSt, C-36-84) is not 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-Tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt) is not classified for aspiration toxicity based on its reported kinematic viscosity at 40 °C.

Key value for chemical safety assessment

Additional information

There are several studies available on the acute oral toxicity of poly alpha olefins. Key studies were identified for the following substances: dec-1-ene, dimers, hydrogenated; 1-dodecene dimer with 1-decene, hydrogenated; 1-decene trimer, hydrogenated and tetramers; 1-decene, homopolymer, hydrogenated; decene trimer hydrogenated; Alkane 4 (i.e., 1-dodecene trimer, hydrogenated, a structural analogue); and Alkane 5 (i.e., 1-decene 1-dodecene homopolymer, a structural analogue). Summaries of these studies are presented below. 

 

Acute Oral Toxicity

One key study was identified for dec-1-ene, dimers, hydrogenated (Doyle, 1988). In this study, Emery 3002 was administered neat, at a dose of 5000 mg/kg to a group of five male and five female Sprague-Dawley albino rats. Following dosing, the animals were observed for gross signs of systemic toxicity and mortality several times on the day of dosing and at least once daily until study termination on day 14. All rats were sacrificed at the end of the study and received a gross necropsy.

 

There was no mortality observed in either male or female Sprague-Dawley rats at the limit dose tested. Animals exhibited mild depression and oily and/or scruffy hair coats until day 3 or 4 of the post-dosing observation period. Gross necropsy did not reveal any significant treatment-related findings. Based on these results, Emery 3002 is not considered to be acutely toxic to Sprague-Dawley rats via oral administration.

 

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.

 

One key study was identified from 1-decene trimer, hydrogenated and tetramers. In this study, one group of five fasted Sprague-Dawley albino rats/sex were given a single oral dose of Emery 3004 (undiluted) at a dose of 5000 mg/kg bw and observed for 14 days (Doyle, 1988).  No deaths occurred during the observation period. Clinical changes noted included mild transitory depression and oily and/or scruffy hair coats, which disappeared by the third day in females and the fourth day in males. Necropsies revealed a small spleen and thickened stomach lining in one rat. No other treatment related clinical signs, necropsy findings or changes in body weight were observed. Based on the lack of clinical findings, the acute oral LD50 was determined to be >5000 mg/kg bw for male and female rats.

 

One key study (Doyle, 1988) was identified from 1-decene, homopolymer, hydrogenated. In this study, groups of fasted, Sprague-Dawley derived albino rats (5 rats/sex) were given a single oral dose of undiluted emery 3006 at a limit dose of 5000 mg/kg bw and observed for 14 days. No mortalities occurred during the study. Clinical observations included transient mild depression and oily hair coats. Animals appeared grossly normal by day 5 post-exposure. Gross necropsy at the end of the 14 day observation period revealed a yellow-brown spot on the stomach lining in one rat. No other gross pathological findings were noted. Based on these results, the acute LD50 value for Emery 3006 is greater than 5000 mg/kg in male and female rats.

 

One key study (Pooles, 2009) was identified from decene trimer hydrogenated. In this acute oral toxicity study, groups of fasted, five 12-week old Sprague-Dawley females were given a single oral dose of neat linealene dimmer A-30H at a limit dose of 2000 mg/kg bw and observed for 14 days. There were no mortalities, clinical signs of toxicity, body weight effects, or gross lesions observed. The oral LD50 was determined to be > 2000 mg/kg in females.

 

One key study (Driscoll, 1995) was identified from Alkane 4. In this study, one group of five fasted Sprague-Dawley rats/sex were given a single oral dose of Alkane 4 (undiluted) at a dose of 5000 mg/kg bw and observed for 14 days.  There was no mortality or clinical signs of toxicity observed. Body weight did not appear to be affected by treatment. There were no abnormalities observed at necropsy. Based on these results, the oral LD50 for Alkane 4 is greater than 5000 mg/kg in rats.

 

For acute oral toxicity, one read-across study from Alkane 5 was identified. In this study, 5 male and 5 female Sprague-Dawley rats were treated with 5000 mg/kg of Alkane-5 via oral gavage (Driscoll, 1995). The animals were observed for mortality and overt signs of toxicity at 1, 2.5, and 4 after dosing and daily once until study termination on day 14. Individual animal body weights were recorded on day 0 and day 14 of the study. At the end of the study period all animals were sacrificed and received a full necropsy. None of the treated animals died over the course of the study. Gross necropsy reported no signs of systemic toxicity or abnormalities. The acute oral median lethal dose of Alkane 5 was reported to be greater than 5000 mg/kg bodyweight.

 

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 and structural analogues. Key studies were identified for the following substances: dec-1-ene, dimers, hydrogenated; 1-dodecene dimer with 1-decene, 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.

 

One key study (Dougherty, 1989) was identified for 1-dodecene dimer with 1-decene, hydrogenated. In the identified study from dec-1-ene, dimers, hydrogenated, 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.

 

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: C8/10/12-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 Alkane1(1 -octene dimer, hydrogenated; a structural analogue most similar to C8/10/12-based PAO2, C16, kinematic viscosity at 40 degrees Celsius 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) 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 tetramers, 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 1-octene dimer, hydrogenated (a structural analogue most similar to C8/10/12 -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 (C8/10/12-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 ° 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-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36 -84 fraction (consisting of 50 wt% or more of species of same M Wt)(kinematic viscosity = 39.57 cSt, C-36-84), does not require classification for acute inhalation toxicity as defined by EU Dangerous Substance Directive 67/548/EEC or 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. The reported kinematic viscosity value for 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt) at 40°C is 39.57 cSt (INEOS, 2010). This value exceeds the discriminating thresholds for classification for aspiration toxicity under EU Dangerous Substance Directive 67/548/EEC (< 7 cSt) and under CLP Regulation 1272/2008 (GHS aligned) (< 20.5 cSt). Therefore, 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt) is not classified for aspiration toxicity. 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 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 data discussed above, 1-tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt) 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 (GHS aligned) because the reported LD50/LC50 values for this substance or its structural analogues exceed the threshold for classification defined in the regulations.  

1-Tetradecene, polymer with 1-dodecene, distn. residues, hydrogenated, C36-84 fraction (consisting of 50 wt% or more of species of same M Wt)

is not classified for aspiration toxicity under EU Dangerous Substance Directive 67/548/EEC or CLP Regulation 1272/2008 (GHS aligned) based on its reported kinematic viscosity of 39.57 cSt at 40 °C.