Registration Dossier

Administrative data

Description of key information

Skin and eye irritation:

Skin or eye irritation studies are not technically feasible as the substance is a gas at room temperature.

Respiratory irritation:

In animal studies, very slight to slight rhinitis is reported following exposure to ethylene for 28 to 90 days. However there is no reported evidence of irritation in humans, including its extensive use as an inhalation anaesthetic during the 1920-1940 time period. Therefore the weight of evidence indicates that any irritant properties of ethylene must be weak.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no study available

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin and Eye irritation

Non-human data

Studies are not technically feasible as the substance is a gas at room temperature.

 

Human data

There are no data available despite widespread industrial and medical use.

 

Respiratory irritation

Non-human data

Minor evidence of respiratory tract irritation is reported in rats following repeated inhalation exposures at high concentrations (Dow 2010). The findings were limited to the upper respiratory tract and described as a bilateral, eosinophilic rhinitis with mucous cell hyperplasia/hypertrophy (MCH) and occasional epithelial hyalinosis. The changes occurred at all exposure concentrations (300 - 10,000 ppm, equivalent to 344.2 - 11,473 mg/m3) and were described as very slight or slight, with only a slight increase in severity at the highest concentration of 10,000 ppm. The authors reported the “change would neither be expected to significantly affect the function of the specific organ/tissue nor have a significant effect on the overall health of the animal” and this is supported by the lack of clinical findings on the study.

In a subsequent study (The Dow Chemical Company, 2012), repeated exposure to ethylene (0, 10, 50, 300 or 10,000 ppm for up to 4 weeks) was associated with a generally concentration and time dependent increase in minimal to mild inflammatory changes in the rat nasal respiratory mucosa. The changes (LOEC = 10 ppm) were generally site specific, co-located and limited to the upper respiratory tract, and resolved following a 13 week non-exposure period.

In a further study the reproducibility of nasal pathology findings and differences in rat strain sensitivity were investigated. Male Fischer 344 and Wistar Han rats were exposed to target ethylene concentrations of either 0 or 10,000 ppm for 4 or 13 weeks (Hamner Institute 2009, Harkema 2010). There were no adverse clinical findings and the histopathological findings were described as similar to those reported in Dow 2010. However the ethylene induced inflammatory and epithelial lesions showed time dependency with effects after 4 weeks less severe than those seen following 13 weeks exposure. In addition strain-differences were seen after 13 weeks of exposure, with F344 rats having a higher incidence and severity of nasal lesions compared to Wistar rats of similar age and gender. Mucous cell hyperplasia/hypertrophy (MCH) was not detected in the Wistar rats.

 

In two previous rat studies (Rhudy 1978 and Hamm 1984) no gross or histopathological alterations which could be attributed to ethylene exposure were seen following ethylene exposure up to 10,000 ppm for 13 weeks or 3000 ppm for 24 months.

 

Overall, results from recent repeat dose inhalation studies suggest that ethylene may cause mild respiratory tract irritation with evidence of very slight or slight rhinitis observed histologically at exposures of 10 ppm (11.47 mg/m3) and above.

 

Human data

Livingstone (1945) reviewed ethylene’s wide use as an anaesthetic from 1923 onwards. The standard mixture administered was 80% ethylene and 20% oxygen, and the authors reported no increase in mucous secretions or signs of irritation in the pulmonary endothelium.

Summary table of non-human and human respiratory irritation studies

 Non-human studies Human studies 
 Dow (2010)  Livingstone (1945)
 The Dow Chemical Company (2012)  
 Hamner Institute (2009)  
 Harkema (2010)  
 Rhudy (1978)  
 Hamm (1984)  

Justification for classification or non-classification

There is no evidence of any significant eye, skin or respiratory tract irritation in humans which would warrant classification. Ethylene-induced rhinitis has been reported in rats after repeated exposures of 28 - 90 days duration although the effects were very slight in nature and showed significant strain differences. Therefore the weight of evidence indicates that any irritant properties of ethylene are weak and require prolonged repeated exposures, with no classification warranted under CLP.