Registration Dossier

Administrative data

Description of key information

Ethylene has low acute inhalation toxicity, the LC50 in rats is > 57,000 ppm (equivalent to >65,400 mg/m3). Anaesthesia in humans is seen at concentrations of 80% ethylene (800,000 ppm or 917,000 mg/m3). In accordance with Section 2 of REACH Annex XI, studies via the oral and dermal route do not need to be conducted 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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published in peer reviewed literature, non-guideline animal experimental study. Predates implementation of GLP. Limitations in reporting but scientifically acceptable and otherwise adequate for assessment.
Qualifier:
no guideline available
Principles of method if other than guideline:
Single acute ethylene exposure (4 hrs) (following 3 day gavage pre-treatment with Arochlor 1254).
GLP compliance:
no
Test type:
other: LC50
Limit test:
no
Species:
rat
Strain:
other: Holtzman
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: 170-250 g
- Weight at study initiation: No data
- Housing: 5 or 6 per cage
- Diet: Purina rat chow (Ralston Purina Co., St Louis, Mo, USA), ad libitum except during exposure
- Water: ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- No data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Animals were exposed using inhalation chambers as described by Leach (1963); modified to allow regulation of the interior temperature.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber concentrations were monitored using a gas chromatograph with a flame ionization detector and a 5 foot column of Porapak Q.
- Samples taken from breathing zone: no data
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatograph
Duration of exposure:
4 h
Concentrations:
10000, 25000, or 57000 ppm (11, 473, 28700 or 65400 mg/m3)
No. of animals per sex per dose:
7
Control animals:
yes
Details on study design:
- Male rats were administered Aroclor 1254 (300 µmole/kg) via gavage, once daily for 3 days, prior to inhalation exposure to ethylene
- Animals were exposed on the 4th day for 4 hours
- Duration of observation period following administration: Animals were killed 24 hrs following exposure
Statistics:
 Dose-response data were analyzed using analysis of variance (ANOVA) where p <0.05 was considered significant.
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 57 000 ppm
Exp. duration:
4 h
Remarks on result:
other: no mortality at highest dose tested
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 65 400 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: no mortality at highest dose tested
Mortality:
None (0/7) each dose level
Clinical signs:
other: None reported
Body weight:
Not reported
Gross pathology:
None done

The authors report that rats that were exposed to ethylene, but not pre-treated with Aroclor, showed no observable changes in the liver (no further detail or animal numbers reported).

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: other: EU (DSD)
Conclusions:
The acute inhalation toxicity (4 hour) of ethylene is >57000 ppm ( 65400 mg/m3 or 65.4 mg/L).
Executive summary:

This study was not conducted with the intention of determining an LC50 value. However, acute toxicity via the inhalation route (4 hrs) was assessed following high dose exposure to ethylene at 10000, 25000, or 57000 ppm (11, 473, 28700 or 65400 mg/m3). In all cases exposure was preceded by 3 days gavage pre-treatment with Arochlor 1254.

No deaths occurred within the first 24 hrs in any dose group following exposure which suggests that the LC50 (4h) is greater than 57000 ppm (65.4 mg/L).

The authors report that rats that were exposed to ethylene, but not pre-treated with Aroclor, showed no observable changes in the liver. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are limited but adequate data for the assessment of the acute inhalation toxicity data of ethylene. It is not technically feasible to dose via the oral or dermal route since the substance is a gas at room temperature.

Non-human information

Acute toxicity: Oral and dermal

No data are available

 

Acute toxicity: inhalation

Non-human information

Standard inhalation acute toxicity studies have not been conducted on ethylene, but two rodent studies add to the overall weight of evidence for low toxicity via the inhalation route. Guest (1981) exposed rats via inhalation to 10,000 ppm ethylene for 5 hrs. No clinical signs or deaths were reported within the first 36 hrs (when the animals were terminated) and there were no histopathological effects in the liver.

The acute inhalation LC50 (5h) of ethylene in rats is > 10,000 ppm (equivalent to >11,473 mg/m3). Also the NOAEC for histopathological effects on the liver is 10,000 ppm (equivalent to >11,473 mg/m3).

The acute toxicity of ethylene via the inhalation route (4hrs) was also assessed by Connolly (1978) following high dose exposure at 10,000, 25,000, or 57,000 ppm (11,473, 28,700 or 65,400 mg/m3). In all cases exposure was preceded by 3 days of oral gavage pre-treatment with Arochlor 1254. No deaths occurred within the first 24 hrs in any dose group following exposure which suggests that the LC50 (4h) is greater than 57,000 ppm (65,400 mg/m3). No clinical signs of toxicity are reported. The authors report that rats that were exposed to ethylene, but not pre-treated with Aroclor, showed no observable changes in the liver. 

The acute inhalation LC50 (4h) of ethylene in rats is > 57,000 ppm (65,400 mg/m3).

 

Human information

Livingstone (1945) reviewed ethylene’s wide use as an anaesthetic from 1923 onwards. The standard mixture administered was 80% ethylene and 20% oxygen. This concentration was reported to have good anaesthetic properties whilst providing adequate oxygen for patients, but not enough to allow the mixture to explode. Ethylene proved to be an effective anaesthetic, relaxation was moderate but the authors reported no increase in mucous secretions or sign of irritation in the pulmonary endothelium. Post-operative mortality was 1.5%; none of the deaths being considered to be directly due to the anaesthetic agent. Incidences of postoperative nausea and/or vomiting occurred only on the day of surgery.

Anaesthesia in humans was induced by 80% ethylene, equivalent dose of 800,000 ppm or 917,857 mg/m3.

Justification for classification or non-classification

There is lack of exposure to ethylene via the oral or dermal routes because the substance is a gas at room temperature. It has a very low acute hazard following inhalation exposure, and no classification or labelling is required with respect to this end-point under CLP.

Although ethylene has been used historically as an anaesthetic at high concentrations (800,000 ppm) a NOAEC for acute narcosis has not been established. Nonetheless it is classified STOT SE3 (H336 - May cause drowsiness and dizziness) under CLP.