Registration Dossier

Administrative data

Description of key information

Members of the C4 high 1,3-butadiene 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. Data are available on some members of the streams in this category (All CAS numbers are; 68476-52-8, 68477-42-9, 68955-28-2, 87741-01-3, 92045-23-3) and on the component substances (1,3-butadiene, butane, isobutane and butene isomers) and indicate that the acute inhalational toxicity of this category is low. The LC50 values are in excess of 10,000 ppm (22,948 mg/m3), limited data suggests that 1,3-butadiene is not acutely toxic in humans and butane and isobutane are considered to be Generally Recognised as Safe and may be used in food products.

Key value for chemical safety assessment

Additional information

The requirement for data on acute oral and dermal toxicity is waived in accordance with REACH Annex XI, as members of the C4 high 1,3-butadiene category are flammable gases at room temperature.

 

The acute inhalational toxicity of streams in this category (CAS numbers; 68476-52-8, 68477-42-9, 68955-28-2, 87741-01-3, 92045-23-3) is expected to be low. Data are available on the streams and on the component substances.

 

In all cases LC50 values exceed the dose levels which would warrant classification under DPD or CLP. Limited human data also support this conclusion. The category members have the potential to produce narcosis or cause asphyxia by reducing the available concentration of oxygen. Intentional inhalation (abuse) of high concentrations of butane can cause symptoms including euphoria, ataxia, nausea, convulsions, coma, respiratory depression, and even death.

 

Specific data are as follows:

 

Non-human information

 

Streams: The acute inhalation LC50s (4 hour) of Butadiene Concentrate (CAS no. 68955-28-2) and a mixture of C4 gases (no CAS no. specified) in rats were greater than 5300 mg/m3(2331 ppm) (Gulf Oil 1982 and BASF 1980 respectively).

 

1,3-Butadiene: The acute inhalation LC50 in rats is 285,000 mg/m3(128,803 ppm) and in mice is 270,000 mg/m3(122,024 ppm) (Shugaev et al 1969). Rapid onset of narcosis was observed in both species.

 

Butane: LC50 values of 658,000 mg/m3in rats and 680,000 mg/m3in mice were reported (Shugaev et al 1969). Toxicity included anaesthesia, CNS depression, cardiac sensitisation (all rapidly reversible if exposure ceases).

 

Isobutane: No toxic effects were noted below its lower flammability limit of 18000 ppm (42787 mg/m3). Aviado et al (1977) reported the 2 hour LC50 in mice to be 52% (approximately 520,400 ppm or 1237 mg/L), but the same authors tested a mixture of 3 hydrocarbons (isobutane, butane, and propane) and found the LC50 of the mixture comparable to isobutane alone at 57.42% (approximately 539,600 ppm). Both Aviado et al (1977) and Clark and Tinston (1982) demonstrated the range of concentrations required to cause CNS depression/ anaesthesia and those concentrations causing mortality is narrow. There was also evidence of cardiotoxicity including cardiac sensitisation, decreases in both pulmonary compliance and tidal volume but again at dose levels far exceeding the lower flammability limit.

 

Butene isomers (butenes): An LC50 in excess of 10,000 ppm (22,948 mg/m3) has been reported for 2-butene in rats (TNO 1992a). No clinical signs were seen and normal growth occurred over the 14 day observation period. No abnormalities were observed at gross necropsy. These results are also supported by data from Virtue (1950). 1-Butene, cis and trans 2-butene and 2-methylpropene at 27.2, 25.5, 21 and 32% (approximately 624,000; 580,000, 480,000 and 734,000mg/m3) respectively produced respiratory arrest in mice after exposure for 10 min. No clinical observations were seen, other than narcosis, during or after exposure.

 

 

Human information

 

1,3-Butadiene: Limited data suggests that humans can tolerate an exposure concentration of 17,702 mg/m3(8000 ppm) for 8 hours without adverse symptoms (Carpenter, 1944).

 

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 to 8 hours. No subjective or physiological responses were reported. Fatality data are reported for butane where inhalation occurs as a result of intentional misuse. Butane gas may be inhaled during intentional misuse. 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 (bag over head), aspiration of vomit or trauma. The Netherlands Health Council (2004) also summarise several individual cases or retrospective studies in which butane was identified as the fatally toxic agent.

 

Butene isomers (butenes): There are no acute toxicity data in humans.

Justification for classification or non-classification

Members of the C4 high 1,3-butadiene category are flammable gases at room temperature and therefore inhalation exposure is the only relevant route. There are sufficient data available on the streams and component substances to conclude that streams within the C4 high 1,3-butadiene category are of low acute toxicity by the inhalation route with LC50 values in all cases exceeding the doses which would warrant classification under Dir 1999/45/EC or GHS/CLP.