Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data is available on the above endpoint. It is considered appropriate to utilise human data in the absence of an animal study, on the basis of Annex XI on general rules for adaptation of the standard testing regime set out in Annexes VII to X, specifically section1.1.3. Historical human data. This states that:

 

Historical human data, such as epidemiological studies on exposed populations, accidental or occupational exposure data and clinical studies, shall be considered.

 

The strength of the data for a specific human health effect depends, among other things, on the type of analysis and on the parameters covered and on the magnitude and specificity of the response and consequently the predictability of the effect.

 

Taking account of the data set available, assessment against the relevant criteria for assessing the adequacy of the data is as follows:

 

1) the proper selection and characterisation of the exposed and control groups;

 

Evidence is presented for both exposed (pre-sensitised) and control groups. 

 

2) adequate characterisation of exposure;

 

Exposure is categorised in both studies via use of patch testing. This is considered “worst case” as the gaseous form of the substance would not persist for the length of time utilised in the assessments themselves.

 

3) sufficient length of follow-up for disease occurrence;

 

One study quotes a 3 month follow up time, with no effects.

 

4) valid method for observing an effect;

 

The results are adequately categorised. In addition, one study is presented by the World Health Organisation as justification for non-sensitisation potential. Hence the study is considered valid.

 

5) proper consideration of bias and confounding factors; and

 

Both reports consider bias (such as pre-sensitisation to CFC’s). 

 

6) a reasonable statistical reliability to justify the conclusion.

 

A large enough study group is utilised in order to obtain the necessary results and conclusions.

 

The literature data is included for reference.

 

Skin sensitisation

 

Two data sources are available; both giving a non sensitisation endpoint in humans. 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 patients and controls who had not demonstrated sensitivity to CFC-12 previously. One 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.

 


Migrated from Short description of key information:
Assessment of skin sensitisation in humans.

Justification for selection of skin sensitisation endpoint:
Please refer to section 7.10.4 - Sensitisation data (humans) for further information.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data is available on the above endpoint. As these studies are considered to be supporting data only full justification in accordance with the criteria of Annex XI is not provided.

 

Respiratory sensitisation

 

Two data sources are available; both giving a non sensitisation endpoint in humans. The results suggest that chlorofluorocarbons can decrease bronchial tone in asthmatic patients, but that this effect is transient and of a sufficiently small magnitude to be superseded by the dilating effects of fenoterol when both fenoterol and chlorofluorocarbon propellants are inhaled together.

 


Migrated from Short description of key information:
Assessment of respiratory sensitisation in humans.

Justification for selection of respiratory sensitisation endpoint:
Please refer to section 7.10.4 - Sensitisation data (humans) for further information.

Justification for classification or non-classification

The above studies have all been ranked reliability 2 according to the Klimish et al system. This ranking was deemed appropriate because the studies were not conducted to GLP and are not in compliance with agreed protocols. However, as human tests, these are considered appropriate for use in assessment purposes in accordance with the criteria listed in Annex XI. As such, it is deemed appropriate to apply a weight of evidence approach based on similarity and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for sensitisation effects is therefore required.