Registration Dossier

Administrative data

Description of key information

Acetylene has low inhalation toxicity, the LOAEC for mild intoxication in humans with no residual effects is 107,000 mg/m3.  There are no data on oral and dermal toxicity (studies are not technically feasible as the substance is a gas at room temperature). 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Limitations with regard to the test method and/or reporting but contributing to a weight of evidence approach
Qualifier:
no guideline followed
Principles of method if other than guideline:
No details of principles of method given
GLP compliance:
no
Test type:
other: single exposure of at least 2 hours
Limit test:
no
Species:
rat
Strain:
other: white rat (strain not specified)
Sex:
not specified
Details on test animals and environmental conditions:
Single strain of white rats of uniform weight used.
Route of administration:
inhalation: gas
Type of inhalation exposure:
not specified
Vehicle:
other: air
Details on inhalation exposure:
Duration and method of exposure not reported
Analytical verification of test atmosphere concentrations:
not specified
Remarks on duration:
not reported
Concentrations:
Various concentrations, including 78% and 90% acetylene.
No. of animals per sex per dose:
Not reported
Control animals:
not specified
Details on study design:
The anaesthetic potency and toxicity of various concentrations of acetylene was assessed
Dose descriptor:
other: respiratory failure
Effect level:
90 other: %
Remarks on result:
other: 963,000 mg/m3. Within about 2 hours of the start of exposure (It is assumed this concentration was lethal)
Dose descriptor:
other: anaesthesia
Effect level:
78 other: %
Remarks on result:
other: 834,600 mg/m3. Induced anaesthesia within 15 minutes of the start of exposure but this was not preceded by a marked excitement stage.
Mortality:
Respiratory failure within 2 hours, group size not reported
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Inhalation LC50 rats between 78% - 90% acetylene
equivalent to LC50 780,000 - 900,000 ppm
Executive summary:

The inhalation toxicity of acetylene was investigated in rats. 78% induced anaesthesia within 15 minutes and 90% caused respiratory failure within 2 hours.

Inhalation LC50 rats between 78% - 90% acetylene, equivalent to LC50 780,000 - 900,000 ppm (834,600 - 963,000 mg/m3)

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
834 600 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Non-human information

Acute toxicity: oral

No data available (acetylene is a gas at room temperature and therefore a study does not need to be conducted).

Acute toxicity: inhalation

There are a number of studies providing weight of evidence for low toxicity via the inhalation route in animals. There is no evidence of acute toxicity below the lower explosive limit (LEL) of acetylene which is 2.5% equivalent to 25,000 ppm (UK HPA, 2009). 

Heymans & Bouckaert (1925) exposed dogs by inhalation to atmospheres of 850,000 ppm acetylene for up to 3 hours. Animals showed increases in respiratory volume and frequency and anaesthesia but quickly recovered following removal from atmosphere and there was no mortality. This indicates the acute inhalation LC50 > 850000ppm (909,500 mg/m3).

These findings are supported by Riggs L (1925) who investigated the inhalation toxicity of acetylene in rats. Acetylene air concentrations of 78% induced anaesthesia within 15 minutes and 90% caused respiratory failure within 2 hours. The acute inhalation LC50 rats is therefore estimated to be between 78% - 90% acetylene (equivalent to LC50 834,600 – 963,000 mg/m3)

The toxicokinetics study reported by Ortiz de Montellano & Kunze (1980) (see 5.1.1 above) involved exposure of rats to 10-15% acetylene for 4 hours which they all survived (i.e. no lethality at 15% equivalent to 160,500 mg/m3).  Another of the toxicokinetic studies involved exposure of rats to 5% acetylene (53,500 mg/m3) for 18 hours with no mortality reported (White, 1978).

Considering repeated dose toxicity (see 5.6.3 below), there were no mortalities after 14 and 10 days exposure in rats and guinea pigs (exposure 1 h/day) at 80% acetylene (856,000 mg/m3) (Franken & Miklos, 1933).  Although a higher death rate was reported in rats exposed to 25% acetylene, this was over the period 7-93 days. 

Acute toxicity: dermal

No data available (acetylene is a gas at room temperature and therefore a study does not need to be conducted).

Acute toxicity: other routes

No data available

Human information

Acetylene is viewed as a simple asphyxiant, reducing the amount of oxygen available. Inhalation of acetylene may result in dizziness, headache, weakness, nausea and vomiting (UK HPA, 2009). 

As early as the mid 1920’s it had been reported that acetylene had been successfully used, at very high concentrations, as an anaesthetic in over 2,000 surgical procedures in humans without significant adverse effects (Horwitz, 1923, Davidson, 1925; Goldman and Goldman, 1925; Brandt, 1926, Franken and Schurmeyer, 1928 and Franken, 1930). Alveolar concentration that would result in unconsciousness is, on average, 35% with the concentrations required for anaesthesia for surgery being generally between 70 and 80% (i.e. up to 856,000 mg/m3) (Adriani, 1979).

A group of human volunteers were exposed to acetylene at a range of concentrations in order to assess its anaesthetic properties (Davidson, 1925).  The lowest concentration employed, 10%, caused feelings of mild intoxication and paraesthesia.

Therefore the systemic LOAEC following 1 hour inhalation exposure is considered to be 10% (100,000 ppm or 107,000 mg/m3 equivalent).

Today, the gas is still used in medicine and sport physiology and cardiology but in a rather different way. It is used as part of a clinical technique, often referred to as the inert gas re-breathing technique, to estimate cardiac output. The inert gases used are acetylene, or carbon dioxide or nitrous oxide and when acetylene is used as the blood-soluble inert gas, it is often called the acetylene re-breathing technique. There is a significant amount of literature reporting this procedure by investigators attempting to further understanding of cardiac output changes in humans during, for example, exercise, aging, existence at high altitude, zero gravity, cardiovascular illness and pregnancy and postpartum (Bell et al, 2003; Bell et al, 2001; Warburton et al, 1998; Pierson et al, 2003; Eakin et al, 1993; Johnson et al, 1999; Petrine et al, 1978; Triebwasser et al, 1977; Nystrom et al, 1986; Hoeper et al 1999; Sady et al, 1989; Carpenter et al, 1990; Bogaard and Wagner, 2006).

Typically (Hoeper et al, 1999), with nostrils occluded, a re-breathing bag is filled with a gas mixture, for example, of oxygen nitrogen, carbon monoxide helium and acetylene (3%; 3210 mg/m3). The total bag volume is about 60% of the patient’s vital capacity. The patient completely empties the bag in about 30 s. Cardiac output can be calculated from the rate of disappearance of acetylene from expired air (often measured by mass spectrometry). No reports of significant adverse effects in humans, associated with the acetylene re-breathing procedure have been found in any publications reviewed. 

Additional citations

Bell, C et al (2001). Use of Open-Circuit Acetylene Breathing To Estimate Sub-Maximal and Maximal Cardiac Output: Comparison With Closed-Circuit Acetylene Re-Breathing.  Medicine & Science in Sports & Exercise. 33(5): S300. 

Bell, C et al (2003). Use of Acetylene Breathing to Determine Cardiac Output in Young and Older Adults. Medicine & Science in Sports & Exercise. 35(1):58-64. 

Bogaard HM & Wagner PD (2006). Measurement of cardiac output by open-circuit acetylene uptake: a computer model to quantify error caused by ventilation–perfusion inequality.. Physiol. Meas.271023-1032. 

Brandt T, (1926). Acetylene-oxygen anesthesia is gastric surgery. Anesth. Analg. (Cleveland) 5: 329-36. 

Carpenter MW et al (1990). . Effect of maternal weight gain during pregnancy on exercise performance. Journal of Applied Physiology, Vol 68, Issue 3 1173-1176

Eakin, BL et al (1993). Validation of Acetylene Rebreathing Cardiac Outputs in Adolescents With Congenital Heart Disease Medicine & Science in Sports & Exercise. 25(5): S84. 

Franken H & Schurmeyer A, (1928). (Collapse and anaesthesia – Determining the circulatory blood volume during ether, avertin, and acetylene anaesthesia and its significance). In German. Nark. Anaesth. 1, 437 – 447.

Franken H (1930). Respiration, circulation and musculature during narcosis – Studies on behaviour and effects in man and animals. In German. Arch. Gynaekol. 140, 496 – 553. 

Goldman A and GoldmanJD, (1925). Anesth. Analg. (Cleveland) 4, 211 – 218.

Hoeper MM et al (1999). Determination of Cardiac Output by the Fick Method, Thermodilution, and Acetylene Rebreathing in Pulmonary Hypertension. Am. J. Respir. Crit. Care Med., Volume 160, Number 2, 535-541. 

Horwitz CS (1923). A new general anaesthetic. Lancet Vol. 201, No. 5195, p619. Horwitz, 1923

Johnson, B et al (1999). Open Circuit Acetylene Wash-in Technique for Determining Cardiac Output During Exercise: Comparison With Direct Fick. Medicine & Science in Sports & Exercise. 31(5): S58. 

Nyström J et al (1986). Evaluation of a modified acetylene rebreathing method for the determination of cardiac output. Clin. Physiol. 6: 253 - 268. 

Petrini MF et al (1978). Lung tissue volume and blood flow by rebreathing: theory. J. Appl. Physiol. 44: 795-802. 

Pierson, LM et al (2003). Reproducibility of Cardiac Output in Ramping Exercise Measured By Acetylene Single-Breath Technique. Medicine & Science in Sports & Exercise. 35(5): S143. 

Sady, SP et al (1989). Cardiovascular response to cycle exercise during and after pregnancy. J. Appl. Physiol. 66(l): 336-341. 

Triebwasser JH et al (1977). Non-invasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements. Aviat. Space Environ. Med. 46: 203-209. 

UK HPA (2009): Compendium of Chemical Hazards: Acetylene

Warburton,DERet al (1998). Reproducibility of the acetylene rebreathe technique for determining cardiac output. Medicine & Science in Sports & Exercise. 30(6):952-957. 


Justification for selection of acute toxicity – inhalation endpoint
Respiratory failure in rats, the acute inhalation LC50 estimated to be between 78% - 90% acetylene (equivalent to LC50 834,600 – 963,000 mg/m3). This exceeds the threshold for classification. Therefore, although an effect has been identified, this is not considered relevant for the establishment of a DNEL.

Justification for classification or non-classification

Acetylene does not warrant classification under CLP for acute toxicity via oral, inhalation (LC50 well in excess of LEL of 2.5% and the threshold for classification) or dermal routes of exposure.