Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Taken from publically available data, and is considered accurate based on the registrants experience of the substance.
Type of sensitisation studied:
skin
Study type:
study with volunteers
Qualifier:
no guideline followed
Principles of method if other than guideline:
See "details on study design" below.
GLP compliance:
not specified
Type of population:
general
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: 18
- Sex: Not specified
- Age: Not specified
- Race: Not specified
- Demographic information: Not specified
- Other: N/A
Clinical history:
3 patients with a prior history of skin reactions to deodorant sprays
Controls:
15 patients with no prior history of skin recations
Route of administration:
dermal
Details on study design:
Van Ketel (1976) reported allergic contact eczema in patch tests performed in three patients that had a prior history of skin reactions to deodorant sprays. Fifteen controls (without prior history of allergy to deodorants) were also utilised.
Results of examinations:
Only one patient showed a mild reaction to CFC-12. Fifteen controls (without prior history of allergy to deodorants) showed no response to CFC-12.
Conclusions:
The available data indicates that application of CFC-12 to the skin under patch test conditions did not elicit a sensitisation response. Given the nature of CFC-12 as a gas, conditions resulting in prolonged application to the skin are unlikely to allow for elicitation of a sensitisation response. CFC-12 is a controlled substance due to the participation in the depletion of stratospheric ozone (Montreal Protocol). As a result of this, it is no longer utilised in aerosol sprays, hence repeated exposure is unlikely. In the event of accidental exposure to the skin, rapid volatilisation will result in removal from the affected area, thus reducing the potential to cause sensitisation via prolonged contact. On the basis of the data available, it is concluded that the substance is not a skin sensitiser.
Executive summary:

Van Ketel (1976) reported allergic contact eczema in patch tests performed on three patients that had prior history of skin reactions to deodorant sprays. Only one patient showed a mild reaction to CFC-12. Fifteen controls (without prior history of allergy to deodorants) showed no response to CFC-12.

The available data indicates that application of CFC-12 to the skin under patch test conditions did not elicit a sensitisation response. Given the nature of CFC-12 as a gas, conditions resulting in prolonged application to the skin are unlikely to allow for elicitation of a sensitisation response. CFC-12 is a controlled substance due to the participation in the depletion of stratospheric ozone (Montreal Protocol). As a result of this, it is no longer utilised in aerosol sprays, hence repeated exposure is unlikely. In the event of accidental exposure to the skin, rapid volatilisation will result in removal from the affected area, thus reducing the potential to cause sensitisation via prolonged contact. On the basis of the data available, it is concluded that the substance is not a skin sensitiser.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Taken from publically available data, and is considered accurate based on the registrants experience of the substance. The study focuses mainly on ethyl chloride but also discusses CFC-12 as a propellant and accounts for subsequent exposures.
Type of sensitisation studied:
skin
Study type:
study with volunteers
Qualifier:
no guideline followed
Principles of method if other than guideline:
Refer to "details on study design" listed below.
GLP compliance:
not specified
Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
- Number of subjects exposed: 1 patient
- Sex: female
- Age: 30-year old

20 control individuals were included
Clinical history:
1 patient with known reactions. For investigations, oral information consent was obtained from the patient. Her medical history included contact allergy to jewellery and an eczematous reaction after the use of a hairspray, while there was no evidence of atopy.
She showed skin reactions following a test for sensory level of anesthesia where ethyl chloride, a halogenated hydrocarbon commonly used as topical anesthetic formulated in the propellant CFC-12. On the first postoperative day she showed erythematous and slightly itchy macules with vesicles where she had been sprayed.
Controls:
20 control patients. For investigations, oral consent was obtained from the patient and control individuals.
Route of administration:
dermal
Details on study design:
The following investigations were performed. Skin prick tests with common respiratory allergens were negative. Patch tests were performed with the European Standard series for pure dichlorodifluoromethane (Provotest). For the test, test chambers with a tissue pad (d= 16mm) covered by a plastic membrane on silk tape (Leukotest) were used, which were previously punctured several times through all layers with a thick injection needle. The tissue pads were vigorously sprayed with the aerosol until they were saturated or frozen. In order to avoid cold damage, patches were not applied to the back of the patient until the moment that they had thawed. The gas that instantly forms upon skin contact was allowed to evaporate through the prepared holes. Readings of the test results were made after 2 and 3 days following the criteria of the ICDRG.
Results of examinations:
A strongly positive crescendo reaction, extended beyond the edges of the tissue pad, to CFC 12 was observed. However, the substance was tested in the same manner in 20 control individuals and was found to be negative. Other medical aerosols containing a smaller amount of CFCs were negative.

Results of patch test - sensitised individual.

Series/Substance

Concentration

D2

D3

Dichlorodifluoromethane (Provotest)

As is

+++

+++

 

Negative in 20 control individuals.

Conclusions:
The available data indicates that application of CFC-12 specifically to the skin under patch test conditions did not elicit a sensitisation response in the 20 controls who had not demonstrated sensitivity to CFC-12 previously. The report details a case of acute allergic contact dermitis following the exposure in the pre-sensitised individual only; all control subjects elicited no response in both a skin prick and standard patch test.
Given the nature of CFC-12 as a gas, conditions resulting in prolonged application to the skin are unlikely to allow for elicitation of a sensitisation response. CFC-12 is a controlled substance due to the participation in the depletion of stratospheric ozone (Montreal Protocol). As a result of this, it is no longer utilised in aerosol sprays, hence repeated exposure is unlikely. In the event of accidental exposure to the skin, rapid volatilisation will result in removal from the affected area, thus reducing the potential to cause sensitisation via prolonged contact. On the basis of the data available, it is concluded that the substance is not a skin sensitiser.
Executive summary:

The available data indicates that application of CFC-12 specifically to the skin under patch test conditions did not elicit a sensitisation response in the 20 controls who had not demonstrated sensitivity to CFC-12 previously. The report details a case of acute allergic contact dermitis following the exposure in the pre-sensitised individual only; all control subjects elicited no response in both a skin prick and standard patch test. 

Given the nature of CFC-12 as a gas, conditions resulting in prolonged application to the skin are unlikely to allow for elicitation of a sensitisation response. CFC-12 is a controlled substance due to the participation in the depletion of stratospheric ozone (Montreal Protocol). As a result of this, it is no longer utilised in aerosol sprays, hence repeated exposure is unlikely. In the event of accidental exposure to the skin, rapid volatilisation will result in removal from the affected area, thus reducing the potential to cause sensitisation via prolonged contact. On the basis of the data available, it is concluded that the substance is not a skin sensitiser.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Key value taken from published data. 
Boiling point at 101 325 Pa:
-29.8 °C

Six references are available for inspection. The reference values closely matches the registrants experience of the substance and is considered suitable for use, on the basis of a weight of evidence approach.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion