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Description of key information

One key acute oral toxicity studies (OECD 423) was identified. Two acute dermal toxicity studies (OECD 402) were identified from 1-dodecene dimer with 1-decene, hydrogenated (OECD 402) and another from Alkane 4 (OECD 402), a structural analogue.  Additional read-across studies were identified for numerous poly alpha olefins that showed similar acute oral and dermal toxicity results.  
Eight acute inhalation toxicity studies (OECD 403) were identified for poly alpha olefins and used to build a weight of evidence case. 1-Decene trimer, hydrogenated and tetramers (kinematic viscosity = 15-20 cSt, C-30 and 40) is not classified as an acute inhalation hazard based on a weight of evidence analysis relying on viscosity, major carbon number, and reported LC50 values for poly alpha olefins.
1-Decene trimer, hydrogenated and tetramers is classified as an aspiration hazard based on its reported viscosity at 40° C.

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 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).  Exposure was conducted under occlusive conditions.

 

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.

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-dodecene dimer with 1-decene, hydrogenated; 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.
  • The oral LD50 was > 5000 mg/kg bw in male and female rats for dec-1-ene, dimers, hydrogenated.
  • The oral LD50 was > 5000 mg/kg bw in male and female rats for 1-dodecene dimer with 1-decene, hydrogenated.
  • The oral LD50 was > 5000 mg/kg bw in male and female rats for Alkane 5.
  • The oral LD50 was > 5000 mg/kg bw in male and female rats for 1-decene, homopolymer, hydrogenated.
  • The oral LD50 was > 2000 mg/kg bw in male and female rats for decene trimer hydrogenated

These results indicate that 1 -decene trimer, hydrogenated and tetramers 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.

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. Exposure was conducted under occlusive conditions. 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.

Additionally, key studies showing similar results were identified for dec-1 -ene, dimers, hydrogenated and Alkane 5 (a structural analogue). LD50 values for these substances were as follows:

  • 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 Alkane 5.

These results infer that 1 -decene trimer, hydrogenated and tetramers is 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 analogue), and 1-dodecene polymer with 1-decene, hydrogenated.

The acute inhalation toxicity of 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) 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 degrees Celsius = 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 (rales) 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 dyspnea, 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, kinematic viscosity at 40 degrees Celsius = 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 degrees Celsius = 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 degrees Celsius 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 degrees Celsius. 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 degrees Celsius 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 20 or less.

 

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

 

Based on the available LC50 results reported for Alkane 4, 1-decene trimer, hydrogenated and tetramers 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 labelling for aspiration toxicity relies on the measured or calculated kinematic viscosity of a substance at 40°Celsius rather than results from toxicological studies with animals. The kinematic viscosity for 1-decene trimer, hydrogenated and tetramers at 40 degrees Celsius is 15 -20 cSt (Exxon Mobil, 2010). This value exceeds the discriminating threshold of 7 cSt established for classification and labelling set forth in EU DSD/DPD 67/548/EEC but falls below the discriminating threshold of 20.5 cSt established for EU CLP Regulation 1272/2008 (GHS aligned). It is therefore classified and labelled as a Category 1 aspiration toxicant; H304: May be fatal if swallowed and enters airway according to EU CLP. 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-decene trimer, hydrogenated and tetramers 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-Decene trimer, hydrogenated and tetramers is not an aspiration toxicant according to EU DSD. However, it is classified 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).