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Description of key information

Members of the Other Petroleum Gases category are all 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. There are no specific studies on the streams within the Other Petroleum Gases category but data are available on the component substances. Across species, main component gases in this category (C1-C4 alkanes and propene) 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. The mammalian toxicity effects of this category will be not driven by the content of benzene as the latter is present at levels of <0.3%, however, the category may contain carbon monoxide and/or hydrogen sulphide which could trigger classification. 

Key value for chemical safety assessment

Additional information

No specific acute toxicity data are available on any of the streams within this category; however acute toxicity data are available for the major components of the category, namely the C1-C4 alkanes and propene.

 

Acute oral and dermal toxicity

Members of the Other Petroleum Gases 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 major components of the category 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 Other 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.

 

Propene CAS Number 115-07-1

 

The acute toxicity of propene has been studied in several non-guideline experimental animal studies because of its potential use as an anaesthetic. From the available data it is clear that there is no significant difference, across species, in the effects of propene or at the concentrations at which anaesthesia occurs (approx 40% propene: 688,000 mg/m3). 

 

Human information

Oral and dermal toxicity

No quantitative acute oral or dermal data were identified. However direct contact with liquefied gas products can cause burns or frostbite.

 

Inhalation toxicity

The data suggest that at high concentrations, asphyxiation can occur as a consequence of oxygen deficiency. Symptoms of exposure to high levels of Other Petroleum Gases components 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)).

 

Because of its potential use as an anaesthetic, there are literature reports of the acute effects of propene at high concentrations in humans (Khan and Riggs, 1931, Hasley, 1926). There is no significant difference, across species, in the effects of propene or at the concentrations at which anaesthesia occurs (approx 35 and 40% propene: 602,000 -688,000 mg/m3). Recovery of the subjects from anaesthesia was rapid. Mild symptoms were reported, for example vomiting. Despite the high concentrations required for anaesthesia, there were no significant side effects reported.

 

Summary

There are no specific studies on the streams of the Other Petroleum Gases category but data are available on the main component substances(C1-C4 alkanes and propene). 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. There is no significant difference, across species, in the effects of propene or at the concentrations at which anaesthesia occurs (approx 40% propene: 688,000 mg/m3). 

The mammalian toxicity effects of this category will be not driven by the content of benzene as the latter is present at levels of <0.3%. However, Other Petroleum Gas streams may contain carbon monoxide and/or hydrogen sulphide, levels of which could trigger classification.

 

Carbon Monoxide CAS number 630-08-0

(Classification: EU-R23; GHS/CLP - Cat 3 H331)

The World Health Organisation published an extensive review of carbon monoxide in 1999 (WHO, 1999, updated 2004). In the human body, it reacts readily with haemoglobin to form carboxyhaemoglobin (COHb). Its toxic effects on humans are due to hypoxia, which becomes evident in organs and tissues with high oxygen consumption such as the brain, the heart, exercising skeletal muscle (and the developing foetus). At a COHb level of about 10%, carbon monoxide has no appreciable effect except shortness of breath upon exertion, at 20% it is likely to cause headache and shortness of breath, at 30% there will be also dizziness, nausea and vomiting. At a COHb level of about 40%, carbon monoxide starts to cause coma and collapse, and at 50–60% the poisonings are often lethal. Across species a range of LC50 values exist, dependent upon time of exposure, therefore the lowest dose concentration for Cat 3 H331 (acute tox range 500 to 2500 ppm for gases) is assumed as worst case scenario for classification and labeling purposes. 

 

Reference

World Health Organisation, 1999

Environmental Health Criteria 213 (Carbon Monoxide, second edition)

1999, updated 2004

 

Hydrogen Sulphide CAS 7783-06-4

(Classification: EU-R26; GHS/CLP -Cat 2 H330)

 

Hydrogen sulphide has been reviewed by the IPCS for WHO in 2003. Human exposure to the gas is principally via inhalation, and the gas is rapidly absorbed through the lungs. Adverse health effects in humans exposed by inhalation for short periods include respiratory and neurological effects; death may result as a consequence of respiratory failure. It is also an ocular and respiratory tract irritant. There are no data on longer term exposure of humans to the gas but animal data showed that respiratory effects are the most sensitive end-point. Insufficient data exist with which to evaluate the carcinogenic or genotoxic potential of hydrogen sulphide. A range of LC50 values exist, dependent upon time of exposure, therefore the lowest dose concentration forCat 2 H330 (acute tox range 100 to 500 for gases) is assumed as worst case scenario for classification and labeling purposes. 

 

Reference

World Health Organisation

Hydrogen Sulphide: Human Health Aspects

Concise International Chemical Assessment Document 53, 2003

Justification for classification or non-classification

Since all 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 major components of the Other Petroleum Gases category (the C1-C4 alkanes and propene) are of low acute toxicity by the inhalation route with LC50 values far exceeding the dose levels which would warrant classification under DPD (Dir 1999/45/EC) or GHS/CLP.

The mammalian toxicity effects of this category will be not driven by the content of benzene as this is present at less than 0.3% w/w and therefore exempt from classification/hazard assessment based on this substance (levels of >10% would trigger EU – R65; GHS/CLP: Category 1, H304).

If present in streams, carbon monoxide is acutely toxic to humans due to its ability to react haemoglobin to form carboxyhaemoglobin (COHb). Its toxic effects on humans are due to hypoxia which becomes evident in organs and tissues with high oxygen consumption.

Consequently category streams that contain carbon monoxide up to a level of 1% should be classified as follows:

EU: Xn, R20 if >0.5% (but <5%).

GHS/CLP: No classification triggered if present at less than 1% concentration.

 

If present in streams, hydrogen sulphide is also acutely toxic to humans. Consequently category streams that contain up to but less than 1% hydrogen sulphide should be classified as follows:

EU: T26, T: R23 “Toxic by inhalation” if >0.2 but <1%; Xn R20 “Harmful by inhalation” if >0.02 but <0.2%.

GHS/CLP: Cat H332 “Harmful if inhaled” if >0.5% (but <4%).