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Description of key information

In vivo tests are reported. Although the test method are not in agreement with current official guidelines the results are sufficient to aim the health hazard assessment.
The results show that the skin irritating potential of HCFC 122a has to be considered slight and the substance does not need to be classified as Irritant for the Skin. However, the repeated application of the substance caused dryness and cracks on the skin.
HCFC 122a has eye irritating potential and the classification as Eye Irritant Category 2 is considered appropriate.

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:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The data source is the competent authority, it is considered reliable. Although the test method was not specifically conducted for the assessment of the skin irritating potential, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was conducted in order to assess the skin absorption properties.
The study was conducted in two stages.
At the first stage the substance was applied in a single administration on the skin of the tails of white mice; contact time was 2 hours, after which the tails were washed with soap and water, and the animals were observed for 14 days.
Since the sigle exposure did not cause symptoms of intoxication and death of animals, a repeated applications of the substance for 12 days was included.
At this second stage the substance was applied to the section of rat skin sized 2 x 2 cm, and the application time was 4 hours. In order to prevent evaporation from the skin surface, the studied section of skin was sealed.
GLP compliance:
not specified
Species:
other: mouse and rat
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Duration of treatment / exposure:
1 stage: 2h single exposure
2 stage: 4h/day exposure for 12 days
Observation period:
1 stage: 14 days
2 stage: no data
Number of animals:
no data
Irritation parameter:
other: general assessment
Remarks on result:
other: Repeated application of HCFC 122a to the skin (4h/day for 12 days) caused dryness of the skin followed by development of redness and cracks.
Other effects:
At the end of the experiment, repeated application of refrigerants to the skin (4h/day for 12 days) caused dryness of the skin followed by development of redness and cracks.
Interpretation of results:
GHS criteria not met
Remarks:
Possible irritant effect after repeated application. Criteria used for interpretation of results: EU
Conclusions:
Repeated application of HCFC 122a to the skin (4h/day for 12 days) caused dryness of the skin followed by development of redness and cracks. The effects did not meet criteria for classification as a skin irritant but warrant a supplemental hazard statement (EUH066 - Repeated exposure may cause skin dryness or cracking).
Executive summary:

The objective of the research was to study the toxicity of HCFC 122a and HCFC 132 and to characterize their biological action in order to validate the approximate safe level of these compounds in the air of working area, ambient air, and water. In this study both a review of the available toxicological data on similar chemical compounds was made and toxicological tests on HFCF 122a and HCFC 132 were performed, including studies of skin-absorption, eye irritating and sensitizing properties.

Information on the potential skin irritating properties of HCFC 122a can be obtained from the study of skin absorption.

The study of skin- absorption properties of the substances was conducted in two stages. At the first stage of the experiment, the toxicity of HCFC 122a and HCFC 132 was studied after application of the substances on the skin of the tails of the white mice; contact time was 2 hours, after which the tails were washed with soap and water, and the animals were observed for 14 days.

Single exposure to the substances did not cause symptoms of intoxication and death of animals. Therefore, experiments with repeated applications of HCFC 122a and HCFC 132 for 4 hours/day for 12 days were included.

At the second stage of the experiment, the ability of the substances to penetrate the skin was investigated. The substances were applied to the section of rat skin sized 2 x 2 cm. In order to prevent evaporation of the substances from the skin surface, the studied section of skin was sealed. The functional state of the experimental animals was assessed based on some physiological parameters.

Study showed that repeated application of the two substances to the skin did not lead to changes in appearance and behaviour of animals and changes in functional parameters, indicating the absence of expressed skin-absorption properties. However, repeated application of both the susbtances to the skin at the end of the experiment caused dryness of the skin followed by development of redness and cracks.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The data source is the competent authority, it is considered reliable. Although the test method is not in agreement with current official guidelines and study details are not fully reported, the results are sufficient to aim a conclusion for the health hazard assessment of the substance.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Two drops of the substance were introducted into the conjunctival sac of the rabbits. Changes were registered after 1, 24 and 72 hours, and 7 days. The degree of damage to the mucous membranes of the eyes caused by these compounds was assessed qualitatively based on changes in the cornea, iris and conjunctiva.
No information on washing are reported. No information on the number of animals and the negative control.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Duration of treatment / exposure:
single administration
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
not reported
Time point:
other: 1 hour
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: palpebral fissure completely closed, diffuse corneal opacity developed, conjunctival hyperemia and inflammatory edema of the eyelids was observed.
Other effects:
Immediately after the application of refrigerants, the animals displayed sharp excitement.
After 1 hour, the palpebral fissure completely closed, diffuse corneal opacity developed, conjunctival hyperemia and inflammatory edema of the eyelids was observed.
After 24 and 72 hours, the severity of the described processes decreased, and a week later the changes almost disappeared.
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Under the reported study, HCFC 122a exhibited irritating effect on the mucous membranes of the eyes.
Executive summary:

The objective of the research was to study the toxicity of refrigerants HFCF 122a and HCFC 132 and to characterize their biological action in order to validate the approximate safe level of these compounds in the air of working area, ambient air, and water. In this study both a review of the available toxicological data on similar chemical compounds was made and toxicological tests on HFCF 122a and HCFC 132 were performed, including studies of skin-absorption, eye irritating and skin sensitizing properties.

To identify the substance action on conjunctiva, the test solutions of HCFC 122a and HCFC 132

were introduced into the conjunctival sac of rabbit eyes; besides, local action of the substances was studied by Draize method.

Two drops of the substances were introducted into the conjunctival sac of the rabbits. Changes were registered after 1, 24 and 72 hours, and 7 days. The degree of damage to the mucous membranes of the eyes caused by these compounds was assessed qualitatively based on changes in the cornea, iris and conjunctiva.

Studies showed that immediately after the application of refrigerants, the animals displayed sharp excitement. After 1 hour, the palpebral fissure completely closed, diffuse corneal opacity developed, conjunctival hyperemia and inflammatory edema of the eyelids was observed. After 24 and 72 hours, the severity of the described processes decreased, and a week later the changes almost disappeared; HFCF 122a caused more severe irritation than HCFC 132.

The study authors established that the test compounds exhibit slight irritating effect on the mucous membranes of the eyes, wherein these properties are more pronounced in HFCF 122a.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Results of an in vivo skin absorption test are reported. HCFC 122a was applied to the section of rat skin sized 2 x 2 cm, the application time was 4 hours and the daily applications were repeated for 12 days, therefore information on the potential skin irritating properties of the substance can be obtained from the reported observations on the state of the skin. During the study, in order to prevent evaporation of the substance from the skin surface, the studied section of skin was sealed. The study showed that repeated application of refrigerants to the skin did not lead to changes in appearance and behaviour of animals and changes in functional parameters, indicating the absence of expressed skin-absorption properties. At the end of the experiment dryness of the skin was observed, followed by development of redness and cracks.

Basing on the results, considering that skin reactions were observed only following many repeated daily applications and considering that the type of coverage was occlusive, which could generate more severe skin reactions or exhibit an irritant effect itself, the irritating potential of HCFC 122a, if any, has to be considered slight and the substance does not need to be classified as Irritant for the Skin.

Results of an in vivo eye irritation/corrosion study conducted according to Draize method are reported. The degree of damage to the mucous membranes of the eyes was assessed qualitatively based on changes in the cornea, iris and conjunctiva, no ocular irritation scores were derived. Under the reported study HCFC 122a exhibited irritating effect on the mucous membranes of the eyes. A week later the instillation the changes due to the substance administration almost disappeared.

Although the test method is not in agreement with current official guidelines and study details are not fully reported in the document, the study result shows an irritating potential of the substance on eye.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: irritating

Respiratory irritation: there were no specific indications of significant irritating effects to the respiratory tract in animals studies (single or repeated administration), or in a volunteer study assessing olfactory effects.

Justification for classification or non-classification

According to Regulation (EU) 1272/2008 classification criteria, skin corrosion means the production of irreversible damage to the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test substance for up to 4 hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Skin Irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

Under the reported study slight adverse reversible effects on the skin were observed following repeated 4h-applications of the substance for 12 day on the rat skin.

However, the effects were observed at the end of the 12 day-experiment, thus exceeding the maximum exposure period of 4 hours set under the CLP criteria for skin irritation. Moreover the type of coverage used under the experiment was occlusive, which results in more rigorous test conditions compared to the semi-occlusive patching used in the current methods for testing skin irritation/corrosion. According to the “Guidance on the Application of the CLP Criteria” the method of application should be accounted in the evaluation of effects, since the occlusive coverage could aim more severe effects.

Considering that the skin reactions were observed only following many repeated daily applications and considering that the type of coverage was occlusive, which could generate more severe skin reactions or exhibit an irritant effect itself, the substance does not need to be classified as Irritant for the Skin. However as the repeated applications resulted in dryness and cracking, the substance meet the criteria for the supplemental hazard statement EUH066- Repeated exposure may cause skin dryness or cracking.

According to Regulation (EU) 1272/2008 classification criteria, serious eye damage means the production of tissue damage in the eye, or serious physical decay of vision, following application of a test substance to the anterior surface of the eye, which is not fully reversible within 21 days of application. Eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

Under the reported study adverse effects on eyes were observed at 1, 24 and 72 hours after administration. Although the observation period was limited to 7 days, the degree of damage to the mucous membranes of the eyes was assessed qualitatively based on changes in the cornea, iris and conjunctiva. Those effects were quite severe and consisted of palpebral fissure completely closed, diffuse corneal opacity developed, conjunctival hyperemia and inflammatory edema of the eyelids. However, since at the 7thday after the substance administration, the changes observed almost disappeared, the conclusion is that the effects would have been completely reversible within 21 days.

Basing on this reasoning the substance has to be classified as Eye Irritant Category 2.