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Description of key information

There were no studies identified for 1-methylbutane for acute oral or inhalation toxicity.  Consequently, read across from n-pentane and cyclopentane was used for this endpoint.  An acute oral (OECD 401 and EU Method B1) and an acute inhalation (non-guideline) toxicity study on n-pentane was identified.  One key acute oral toxicity study (OECD 423) and one key acute inhalation toxicity study (OECD 403) on cyclopentane was identified.  LD50 and LC50 values are as follows:
• LD50 was > 2000 mg/kg in the rat in the acute oral toxicity study for n-pentane.
• LD50 was > 5000 mg/kg in the rat for cyclopentane.
• No mortality was seen at exposures > 20,000 ppm for either rats or mice when exposed to n-pentane for 4 (male animals) or 2 (female animals) hours; an LC50 value was not reported.
• LC50 was > 25.3 mg/L in the rat for cyclopentane.
2-Methylpentane is classified as aspiration hazard based on the kinematic viscosity, 2.75 mm2/sec at 20° C, of pentanes as a category.

Key value for chemical safety assessment

Additional information

Key studies on the acute toxicity of 2-methylbutane were not available.  Acute oral and inhalation studies were identified from n-pentane and cyclopentane. In an acute oral toxicity study with n-pentane, 5 rats per sex were given a single oral dose of undiluted n-pentane (pure) at a dose of 2000 mg/kg (3.33 mL/kg) and were observed for 14 days (Frank, 1996). There were no mortalities or consistent signs of systemic toxicity through the 14 days with no abnormalities noted at necropsy. The estimated LD50 for n-pentane is thus greater than 2000 mg/kg. In an acute oral toxicity study, cyclopentane was administered orally as a single 5000 mg/kg dose to male and female rats (Pence, 1982). Specifics of the treatment and vehicle were not provided. Animals were observed for 14 days; a gross necropsy was then performed. In the first 24 hours, rats exhibited depression or slight depression, red stains on the nose and/or eyes, rough coat, soft faeces, hunched appearance, and urine stains. All animals were normal by day 2. No mortalities occurred during treatment or throughout the 14 -day observation period. There were no treatment-related changes in body weight or gross pathology. Based on the results, the oral LD50 of cyclopentane in male and female rats is greater than 5000 mg/kg.

Collectively, these studies indicate that 2 -methylbutane is not acutely toxic via the oral route as all the reported LD50 values exceed the upper regulatory threshold for classification (2000 mg/kg bw). Therefore, 2 -methylbutane is not acutely toxic by the oral exposure route. It does not meet EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008) for this endpoint.

 

With regard to acute inhalation toxicity, groups of young adult male Wistar strain albino rats (4 per dose level) and female H strain mice (8 per dose level) were exposed by inhalation route to n-pentane for 4 hours (males) or 2 hours (females) to whole body at 3 concentrations. Animals were examined for neurotropic effects, specifically depression of seizure responses after exposure to an electrical impulse. Mortality was not reported, and no long-term systemic effects were reported. No NOAEC was reported, and the LC50 was not calculated. The concentration resulting in 37% depression of the shortening of the tonic extension of hind limbs by 3 seconds in male rats was found to be 21000 ppm (6197 mg/m3), while the concentration resulting in 30% depression of the lengthening of the latency of extension by 0.6 seconds in mice was found to be 23500 ppm.

A key acute inhalation study also was identified for cyclopentane. In this study, 5 albino Sprague-Dawley rats/sex were administered 25.30 mg/L (nominal concentration of 26.40 mg/L) showed no observed mortalities after animals were exposed whole body for 4 hours (Jackson, 1983). Hunched posture was observed in all rats (male and female) during hours 1 to 4 of the exposure period. A few male rats exhibited reduction in bodyweight gain on the day following exposure. Subsequently though, bodyweight gain was similar to that observed in control rats. Food consumption was found to be slightly reduced in male rats for a single day while water consumption seemed unaffected following exposure to cyclopentane. One male rat also exhibited wet fur around the snout and jaws immediately following the exposure period. No macroscopic abnormalities were noted in rats exposed to cyclopentane and individual findings such as basophilic cortical tubules in kidneys, macrophage aggregates, alveolar hemorrhage and pneumonitis in the lungs were considered spontaneous in origin and not treatment-related. Lung to body-weight ratios were found to be within normal limits for all male and female rats. Based on the results discussed above, the 4-hour inhalation LC50 for cyclopentane is >25.30 mg/L.

Collectively, these studies indicate that 2 -methylbutane is not acutely toxic via the inhalation as all the reported LC50 values exceed the upper regulatory threshold for classification (20 mg/L). Therefore, 2 -methylbutanes is not acutely toxic by inhalation. It does not meet EU criteria for classification and labelling (Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008) for this endpoint.

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. Kinematic viscosity is defined as dynamic viscosity (expressed in mPa s)/density (expressed in g/cm3). The reported kinematic viscosity of pentanes as a category is 2.75 mm2/sec at 20° C. Substances with kinematic viscosities less than 7 mm2/sec or 20.5 mm2/sec are classified for aspiration toxicity according to EU DSD and EU CLP regulations, respectively.  2 -Methylbutane, like other pentanes, is 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.

Justification for classification or non-classification

Based on evaluation of all the acute toxicity data discussed above, 2 -methylbutane does not meet the criteria for classification as an acute oral or inhalation toxicant under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 because the LD50/LC50 values reported for these substances exceed the upper discriminating threshold limits for classification defined in the regulations. Although there were no acute studies identified for dermal exposure, physiochemical data suggests that absorption via the dermal route is not significant and that dermal toxicity is not a significant cause for concern. Additionally, it is generally assumed that exposure via the oral route leads to greater absorption of the substance compared with exposures via the dermal route. Oral exposure studies within pentanes did not report any potential for serious or severe toxicity by this route of exposure, therefore it is unlikely that toxicity via dermal exposure poses a significant risk.

2 -Methylbutane, like other pentanes, classified as Xn; R65, harmful (May cause lung damage if swallowed) in accordance with Dangerous Substances Directive 67/584/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 kinematic viscosity of 2.75 mm2/sec at 20° C (this value is representative of pentanes as a category).