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Administrative data

Description of key information

Skin irritation

Hollingsworth et al. (1956): non-guideline, non-GLP study on shaved skin of rabbits using 10% and 50% aqueous solutions, exposure: 1 – 60 minutes. Scar formation observed if treated longer than 6 minutes. Corrosive potential identified.

Eye irritation

The test substance is corrosive to skin and therefore also considered as highly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Occlusive application to shaved rabbit skin for periods of 1 - 60 minutes followed for an observation period of 6-7 days.
GLP compliance:
no
Remarks:
pre-GLP study
Specific details on test material used for the study:
- physical appearance: liquidSOURCE OF TEST MATERIAL
- Purity: 97.0 - 98.6%
- Impurities: Maximum found by MS analysis were 2.3% air and 0.7% acetylene.
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Remarks:
intact skin only
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
10% and 50% aqueous solutions
Duration of treatment / exposure:
1 - 60 min
Observation period:
6 - 7 days
Number of animals:
no data
Details on study design:
Small pads of cotton were moistened with aqueous solutions of ethylene oxide and applied to the intact shaved abdominal skin of immobilized rabbits under a saran plastic cover for periods of time ranging from 1 - 60 minutes. The animals were observed for 6 - 7 days following exposure.
Irritation parameter:
other: hyperemia, edema and scar formation
Basis:
mean
Time point:
other: 6 minutes
Remarks on result:
other: hyperemia and edema resulted when the duration of skin contact was 6 minutes or longer. The severer exposures resulted in scar formation. The intensity of response was roughly proportional to the length of exposure time and concentration.
Irritant / corrosive response data:
Hyperemia and edema resulted when the duration of skin contact was 6 minutes or longer. The longer exposures resulted in scar formation. The intensity of response was roughly proportional to the length of exposure time and the concentration.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Severe injury to the skin was described as the result of contact, in particular with aqueous solutions of ethylene oxide.
Executive summary:

The skin irritation potential of the test substance was investigated using more than a single rabbit exposed to concentrations in aqueous solutions of 10 and 50%. Small pads of cotton were moistened with the test substance and applied to the intact shaved abdominal skin of immobilized rabbits under a saran plastic cover for 1 minute to 60 minutes. Rabbits were observed for six to seven days following exposure. Hyperemia and edema resulted when the duration of the skin contact was six minutes or longer. The intensity of response was roughly proportional to the length of exposure time and the concentration. Scar formation was reported and thus, the test substance was concluded to be corrosive.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation potential of the test substance was investigated using more than a single rabbit exposed to concentrations in aqueous solutions of 10 and 50%. Small pads of cotton were moistened with the test substance and applied to the intact shaved abdominal skin of immobilized rabbits under a saran plastic cover for 1 minute to 60 minutes. Rabbits were observed for six to seven days following exposure. Hyperemia and edema resulted when the duration of the skin contact was six minutes or longer. The intensity of response was roughly proportional to the length of exposure time and the concentration. Scar formation was reported and thus, the test substance was concluded to be corrosive (Hollingsworth et al., 1956).

In addition, a study to both intact and abraded skin of New Zealand White rabbits was performed. Results confirm the corrosive potential of the test substance based on chemical burns and subdermal hemorrhages observed on intact skin of animals (Celanese, 1972). The study was conducted at IBT and was thus not fully included in the assessment process.

Eye irritation

Based on the corrosivity to rabbit skin, ethylene oxide is assessed as highly irritating to eyes without further testing.

There are two sources of information available: One study categorized as Klimisch 2 which cannot be used for classification as only highly diluted concentrations were tested. These dilutions caused in only mild irritation effects (McDonald et al., 1977). Then, handbook information describes ethylene oxide as highly irritating (Klimisch 4).

Consulting the Regulation (EC) No 1907/2006 last amended on 05 Sep 2018, an in vivo serious eye damage/eye irritation study does not need to be conducted if the substance is classified as skin corrosion, leading to classification as serious eye damage Category 1.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The following is quoted from the RAC opinion proposing a harmonized classification and labelling at the EU level of ethylene oxide ( CLH-O-0000001412-86-164/F, adopted 22nd September 2017):

The reports on skin irritation/corrosion include a number of human case reports, describing the

corrosive potential of ethylene oxide. Two animal studies were found. One described clearly the

corrosive potential of ethylene oxide after exposure to undiluted liquid for 4 h. The effects were

observed on intact, as well as abraded skin. The other study reported hyperaemia and oedema

already after 6 min of exposure to 10% or 50% aqueous solution of ethylene oxide. The severity

of effects increased with prolonged exposure time. No details on the test conditions, or scoring

when evaluating the skin irritation, were reported. Both animal studies included exposure under

occlusive conditions. Current standard in vivo tests for skin irritation/corrosion include exposure

under semi occlusive patches. In the CLP guidance, it is stated that “Especially in borderline cases

of classification the method of application should be accounted for in the evaluation of effects”.

RAC considers that the available data provides evidence for the corrosive potential of ethylene

oxide. The 4-h animal study describes outcomes that justify a subcategorisation as Skin Corr. 1C

(criteria: responses occur after exposures between 1 and 4 h and observations up to 14 days).

The study protocol of the other in vivo study, with an exposure time of up to 1 h, is not reported

in detail. It was indicated that effects were observed already after 6 min of exposure, but due to

the lack of details, RAC considers that this study cannot be used as a key study to justify a

classification as Skin Corr. 1B (criteria: responses occur following exposure between 3 min and

1 h). RAC also considers, that the fact that the studies were performed using occlusive patches

makes a detailed interpretation of the study results complicated.

In the CLP Guidance it is stated that “Where the substance is classified as a skin corrosive but

the data used for classification does not allow differentiation between the skin corrosion

subcategories 1A/1B/1C, then the substance should be assigned skin corrosive Category 1”.

On the basis of the arguments presented above, RAC concludes that ethylene oxide should be

classified as Skin Corr. 1; H314 (Causes severe skin burns and eye damage) without subcategorisation.

According to CLP, skin corrosive substances shall be considered as leading to serious eye damage

as well. The hazard statement for skin corrosion addresses also serious eye damage (H314:

Causes severe skin burns and eye damage). Thus, there is no need for comparison of the

available data from one eye irritation study with the classification criteria for eye

damage/irritation.

As ethylene oxide is proposed to be classified as Skin Corr. 1, RAC agrees that it shall also be

classified as Eye Dam. 1; H318. According to CLP, the hazard statement H318 (Causes serious

eye damage) is in these situations not included on the label because of redundancy.