Isobutane

Endpoint summary

Description of key information

Members of the Petroleum Gases category are flammable gases at room temperature and therefore the requirement for data on acute oral and dermal toxicity is waived in accordance with REACH Annex XI. Across species, the gases in this category show low acute inhalation toxicity. Indeed they are practically nontoxic for single exposures below their lower flammability limit, most of which range between 1.8-3.2%, circa 39,000 – 43,000 mg/m3. 

Additional information

Acute toxicity data are available for Petroleum Gases.

 

Acute oral and dermal toxicity

Members of the Petroleum Gases category are flammable gases at room temperature, indeed most will form explosive mixtures with air, and therefore the requirement for data on acute oral and dermal toxicity is waived in accordance with REACH Annex XI.

 

Acute Inhalation toxicity

Non-human studies

Most of the Petroleum Gases have been tested for acute inhalation toxicity, the studies have been conducted over many years and many are pre-guideline. However they are adequate for assessment and all LC50 values far exceed 20 mg/L (20,000 mg/m3). Overall there are sufficient data to adequately assess the acute toxicity of the Petroleum Gases.

 

Methane CAS Number 74-82-8

Methane is practically non toxic but acts as a simple asphyxiant at very high concentrations. Brown et al, 1924, demonstrated in cats that a concentration of 87% (606687 mg/m3) caused anaesthesia, whilst 90% (627,607 mg/m3) caused respiratory toxicity and death.

 

Ethane CAS Number 74-84-0

No quantitative acute toxicity data are available for ethane but it is described as a simple asphyxiant.

 

Propane CAS Number 74-98-6

In 1982 Clark et al demonstrated the acute inhalation LC50 following 15 minute exposure to rats exceeds 800000 ppm (equivalent to 1,442,738 mg/m3 or 1443 mg/L). CNS depression occurred after 10 minutes exposure; EC50 (CNS) 280000 ppm (equivalent to 504,961 mg/m3 or 505 mg/L).

Much of the acute inhalation data on propane are from pre-guideline studies. Nevertheless, Cavender (1994) concluded that the gas shows low toxicity in several species. Serious toxicity includes anaesthesia, CNS depression, cardiac sensitisation (all rapidly reversible if exposure ceases) and eventually asphyxia.

 

Isobutane CAS Number 75-28-5

A number of studies indicate that isobutane has low acute inhalation toxicity, as demonstrated by it being designated as Generally Recognised as Safe for its use as a food additive. No toxic effects are noted below its lower flammability limit of 18000ppm (42787 mg/m3, 42.8 mg/L).

The lowest LC50 value in mice (2 hours) of 41% (410,000 ppm (974 mg/L), is reported by Stoughton and Lamson in 1936. Aviado et al 1977 reported the 2 hour LC50 in mice to be slightly higher at 52% (approximately 520,400 ppm or 1237 mg/L), but the same authors also tested a mixture of three hydrocarbons (isobutane, butane, and propane) and found the LC50 of the mixture at 57.42% (approximately 539,600 ppm) to be comparable to isobutane alone.

Both Aviado et al (1977) and Clark et al (1982) demonstrated the range of concentrations required to cause CNS depression/ anaesthesia and those concentrations causing mortality is narrow. There is also evidence of cardiotoxicity including cardiac sensitisation, and decreases in both pulmonary compliance and tidal volume but again at dose levels far exceeding its lower flammability limit.

 

Butane CAS Number 106-97-8

Shugaev et al 1969 reported LC50 values of 658 mg/L in rats and 680 mg/L in mice.

 

Cavender (1994) confirmed that butane has low toxicity for single exposures below the lower flammability limit. Serious toxicity includes anaesthesia, CNS depression and cardiac sensitisation, all rapidly reversible if exposure ceases.

 

 

Human information

Oral and dermal toxicity

No quantitative acute oral or dermal data were identified. However direct skin contact with liquefied material can cause burns and frostbite due to the extreme cold of the liquid.

 

Inhalation toxicity

Little quantitative data on Petroleum Gases were identified. The data suggest that at high concentrations, asphyxiation can occur as a consequence of oxygen deficiency. Symptoms of exposure to high levels of Petroleum Gases include shortness of breath, dizziness, incoordination and confusion but the effects are fully reversible if exposure stops. Simple alkanes like methane and ethane are described as simple asphyxiants but higher molecular weight gases like propane and butane can also cause central nervous depression. Propane, butane and isobutane are considered by the US Food and Drug Administration to be Generally Recognised as Safe (GRAS) when used as propellants, aerating agents and gases and can be used in food products (PHPV 2001).

In a controlled exposure study, Stewart et al (1977, 1978) exposed adult volunteers to isobutane and isobutane/propane mixtures at concentrations of 250-1000 ppm (594 -2377 mg/m3) for 1 min and up to 8 hours. During the investigations, all volunteers were kept under comprehensive medical surveillance which included cardiac and pulmonary responses. No subjective or physiological responses were reported. Likewise, repeat exposures to isobutane at 500 ppm for 1, 2 or 8 hours, 5 days/week for ten exposures were also without any measurable untoward physiological effect. 

 

Fatality data are reported on the higher molecular weight gases like propane and butane where inhalation occurs as a result of intentional misuse. Abuse of gas fuel occurs mainly in teenagers, and Fuke et al (2002), Sugie et al (2004) and Williams and Cole (1998) all report fatalities through exposure to butane gas from cigarette lighters and hair and deodorant sprays. Williams et al 1998 report the acute effects of human solvent abuse include euphoria, disinhibition, hallucinations, ataxia, nausea, convulsions, coma, tinnitus, cardiac arrhythmias, respiratory depression, and even death. Death may ensue by direct cardiac toxicity (arrhythmias) or central nervous system toxicity (respiratory depression) or indirectly by hypoxia, aspiration of vomit or trauma.

The Netherlands Health Council (2004) summarised several individual cases or retrospective studies in which butane was identified as the toxic agent. Again these reports mostly concern its abuse as an inhalant, by adolescents using lighters or hair/deodorant sprays. Butane abuse is often fatal, mostly due to heart failure (arrhythmias, ventricular fibrillation, asystole) and, in one case, due to multiple organ failure involving the central nervous system, cardiovascular and pulmonary systems, and the liver. Of 39 cases where death was considered to be a direct consequence of inhalant abuse, 13 were considered associated with butane. Butane is reported to induce severe acute neurological signs such as seizure, somnolence, coma or cardiovascular complications such as ventricular fibrillation and asystole. Minor symptoms include nausea, dizziness, vomiting, headache, and sore throat.

 

The Netherlands Health Council (2004) also report propane to have CNS depressant and asphyxiating properties. Out of 52 deaths associated with accidental or intentional inhalation of volatile compounds in Virginia (USA) in the period 1987-1996, 6 cases were due to suicide and 7 to accidental overexposure in, usually, the workplace, but the compounds involved were not specified. Of the remaining 39 cases in which death was considered to be a direct consequence of inhalant abuse, 5 were associated with propane.

Berzins (1995) reported on three human inhalation studies on propane. No signs of toxicity or abnormal reactions were observed when eight men and women exposed at 250 and 1000 ppm (0.45 and 1.8 mg/L) for 1 minute to 8 hours. Exposure to 1000 ppm 8 hours/day for 5 consecutive days, and a brief exposure of unknown duration to 10000 ppm (18 mg/mL) did not cause toxicity in humans. Exposure to 100000 ppm (180 mg/L) caused slight dizziness.

 

Assuming a correlation between the anaesthetic potency of a gas and its air/olive oil partition coefficient, Drummond expected that a concentration of propane of 47,000 ppm (86,500 mg/m3) would induce narcosis in man (Drummond 1993, reported by the Netherlands Health Council (2004)).

 

Summary

Members of the Petroleum Gases category are flammable gases at room temperature and therefore the requirement for data on acute oral and dermal toxicity is waived in accordance with REACH Annex XI. Across species, most component gases in this category show low acute inhalation toxicity; indeed, they are practically nontoxic for single exposures below their lower flammability limit, most of which range between 1.8-2.4%, circa 34,000 – 42,000 mg/m3. Asphyxiation (as a consequence of oxygen deficiency) is a potential risk at high dose levels (far exceeding their lower flammability limit) of petroleum gases. Propane and butane can also cause CNS depression. Isobutane and butane are reported to cause cardiac sensitisation and cardiovascular effects (rapidly reversible if exposure ceases). Intentional inhalation of butane can cause euphoria, disinhibition, hallucinations, ataxia, nausea, convulsions, coma, tinnitus, cardiac arrhythmias, respiratory depression, and even death. Death may ensue by direct cardiac toxicity (arrhythmias) or central nervous system toxicity (respiratory depression) or indirectly by hypoxia, aspiration of vomit or trauma.

 

 

Justification for classification or non-classification

Since all Petroleum Gases are gases at room temperature and pressure consideration of oral and dermal toxicity is not considered relevant in this context. In both human and animal studies Petroleum Gases are of low acute toxicity by the inhalation route with LC50 values far exceeding the dose levels which would warrant classification under DSD or CLP.