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Oral Toxicity

The acute oral toxicity of tertiary butyl alcohol is well understood. In acute oral toxicity studies conducted according to US EPA OPPTS 870.1100, tertiary butyl alcohol had an acute oral LD50 value of 3384 mg/kg bw in male rats, 2743 mg/kg bw in female rats and 3046 mg/kg bw (combined). Based on these data, tertiary butyl alcohol is demonstrated to be a low order of acute toxicity following ingestion. Clinical signs indicating effects on the central nervous system included piloerection, ataxia, decreased limb tone, low carriage, prostration, impaired righting reflex, bradypnea, hypoactivity and lacrimation. Other lesser studies in rats and rabbits support the acute oral LD50 value and the prevalence of clinical signs indicating central nervous system toxicity with high doses of tertiary butyl alcohol.

  

In addition to classification for acute lethality, tertiary butyl alcohol should also be considered for classification as an aspiration hazard based on physical properties. The kinematic viscosity of tertiary butyl alcohol is reported elsewhere in this submission as 2.23 Cst at 45°C.

  

Dermal Toxicity

The acute dermal toxicity of tertiary butyl alcohol is well understood. In an acute dermal toxicity study conducted according to US EPA Guidelines (1978), tertiary butyl alcohol had an acute dermal LD50 value of >2000 mg/kg bw in male and female rabbits. Based on these data, tertiary butyl alcohol is demonstrated to be a low order of acute toxicity following skin contact. Clinical signs indicating effects on the central nervous system included ataxia and prostration. 

Inhalation Toxicity

 

The acute inhalation toxicity of tertiary butyl alcohol is well understood. In an acute inhalation study conducted by a method similar to current OECD Guidelines, tertiary butyl alcohol had an acute inhalation LC50 value of >10000 ppm/4 hours in male and female rats. Clinical signs indicating effects on the central nervous system included dyspnea and prostration, which were observed in all animals during exposure. These same signs, along with generalized weakness, appeared in several animals of each sex during the post-exposure period but were fully reversible by study termination. Gross pathological effects observed at necropsy were limited to focal areas of redness on the lungs.

Other routes

In a study to examine the acute toxicity of tertiary butyl alcohol by the intravenous route, the LD50 of tertiary butyl alcohol was established to be >300 mg/kg bw in male and female Fischer 344 rats. No deaths occurred in either sex at any dose level.

Justification for classification or non-classification

The acute toxicity of tertiary butyl alcohol has been investigated in acute oral, dermal and inhalation studies conducted by methods equivalent or similar to recognized guidelines. For each endpoint, a key study was available for use in classification. Tertiary butyl alcohol is not classified for acute toxicity by the oral or dermal routes under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. A harmonized classification according to Directive 67/548/EEC has classified this substance as harmful by inhalation (Xn, R20) and this has been translated into a harmonized Acute Toxicity Inhalation Category 4 classification according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Although the LC50 data for this substance does not justify existing EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 Category 4 by Inhalation, it is a required classification.

UN GHS defines a fifth category for acute toxicity for chemicals with LD50 values between 2000 and 5000 mg/kg bwt. Therefore, in non-EU countries that adopt UN GHS, this substance may be allocated to Acute Toxicity Category 5.

 

Tertiary butyl alcohol has a harmonised classification as Category 3 Specific Target Organ Toxicity – Single Exposure (STOT-SE ) under the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 for respiratory irritation. In addition, based on the observation of central nervous clinical signs in animal studies during and immediately after exposure by the oral, dermal and inhalation routes, STOT SE 3 classification for narcotic effects is warranted for EU CLP and UN GHS classifications.

 

In accordance with Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, this substance does not meet the criteria for classification as an aspiration hazard.

Tertiary butyl alcohol has a kinematic viscosity of 5.72 cSt at 25 °C and 2.25 cSt at 45 °C, a surface tension of 69.8 mN/m at 20 °C and 22.3 mN/m at 25 °C, is miscible with water, and has a relatively low volatility (vapor pressure of 5.413 kPa at 298 °K and boiling point of approximately 83 °C). This substance is not an n-primary alcohol with 3 to 13 carbon atoms or a ketone with no more than 13 carbon atoms; two chemical classes specifically identified for consideration as a Category 2 aspiration hazard according to UN GHS guidelines. While the low viscosity and low surface tension values for tertiary butyl alcohol raise concern for aspiration potential, its high water solubility would be expected to increase the viscosity and surface tension as a consequence of dilution. Based on a log Kow of <1 and an absence of systemic clinical signs in two acute dermal toxicity studies, tertiary butyl alcohol would not be expected to dissolve into and disperse the lipophilic structures within the cells if presented to lung tissues as a liquid droplet. A conservative evaluation would classify tertiary butyl alcohol as a UN GHS Category 2 aspiration hazard based on surface tension and viscosity alone. While this hazard category is included in UN GHS, there is no corresponding Category 2 classification in EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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