Registration Dossier

Administrative data

Description of key information

The available patch-test results do not support that exposure to Lanolin alcohol will lead to skin sensitization in a “substantial number of persons”. It can not be excluded that a very low level (significantly lower than the estimates based on patch-testing) of individuals might develop skin sensitization to Lanolin alcohols due to increased sensitivity or pre-existing conditions. However, this should be considered a normal population reaction and is observed with many chemicals not classified for skin sensitization. 
In conclusion, a weight-of-evidence evaluation of the available literature does not support a classification for skin sensitization of Lanolin alcohols. This is supported by animal studies referred to in an ICCVAM report and a QSAR evaluation.

Additional information

The available studies on the skin sensitization potential of Lanolin alcohols are all based on patch-testing. In evaluating these studies, the following points have been considered:

 

1) Reliability of the test

2) Confounding factors impacting the test

 

There are no universal guidelines for the performance of patch-tests and evaluation of results. A large degree of subjectivity is possible since the results in many cases are based on a large number of patch tests that have been interpreted by a limited number of dermatologists or other medical personnel. If a qualified skin reading and corresponding analysis of the results has not been done (e.g. if primary irritation rather is being interpreted as a sensitizing reaction), the outcome of these studies might be significantly skewed towards false negatives or false positives. No further assessment regarding appropriateness of the patch-test as a method of allergenicity testing in humans has been done for the sake of this statement. It was assumed that the patch-test is a valid approach to assessing the skin sensitization of a substance in humans. Furthermore, it was assumed that all the studies were performed according to standing protocols in the respective institutions. With a few exceptions, all studies were therefore found reliable and were used in a weight-of-evidence evaluation.

 

Patch-testing for skin sensitization to Lanolin has generally been performed with the pure Lanolin alcohols fraction as this was historically assumed to be the fraction of Lanolin which contained a sensitizing potential. Furthermore, it also allowed for exposure to significantly higher, and unrealistic, concentrations. Accordingly, some of the reactions seen with Lanolin alcohol might reflect primary irritation rather than an allergic reaction. This again would also reflect the experience of the individual reading the skin reaction at the conclusion of the patch-test.

 

The skin sensitization rate ranged from 0.2-6.6% in the studies evaluated. Results from the testing with Amerchol® L-101 have not been included in this range as it is a derivative of Lanolin and not found relevant for assessing Lanolin alcohols. The results from the Seidenari publication have also not been included in this range as it was performed in children and it is not considered to represent the general population. The range of skin sensitization rates is significant. Even within some of the studies (e.g. Warshaw and Landeck) there were large variations when the results were analyzed using time of testing as a factor. It is highly unlikely that these observations represent actual changes in the population as exposure to Lanolin-derived products is not expected to vary significantly within the short time-frames studied. 

 

Questions can be raised whether the subjects tested in the evaluated populations represent a “normal” study population. With the exception of theNielsen and Mennestudy, all studies were performed in patient populations that were diagnosed with various skin ailments (e.g. atopic dermatitis or eczema) or were suspected of having these problems. Even for theNielsen and Mennestudy it is likely that people with prior skin problems would be more likely to perform the test (as it was voluntary and self-administered) than people with no skin problems. This again would introduce bias in the results and potentially overestimate the incidence of allergenicity. It is striking that the lowest incidence of sensitization was found in the study (Nielsen and Menne) which had the most “neutral” study population.

 

It is likely that people with dermatitis due to pre-existing conditions or exposures (e.g. due to occupational exposure to a wide range of industrial chemicals) are more sensitive to patch-testing in general. Although allergic reactions would be expected to be relatively specific to a particular antigen, some cross reactivity is expected. This is especially relevant for substances as Lanolin and Lanolin alcohol as they are relatively complex mixtures with similarity to numerous other products.

 

No animal studies on the sensitization potential of Lanolin alcohols are included in this evaluation. Although, it should be mentioned that the publication by Kligman (1998) do refer to a guinea pig maximization assay (assumedly similar to the Magnusson & Kligman method of OECD 406) that was performed on Lanolin. This study was negative. The ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods) report (Addendum 1 to NIH Pub 99-4494: Revised Draft Assessment of the Validity of the LLNA for Mixtures, Metals, and Aqueous Solutions) also refers to negative results (relative to the EC classification threshold) from LLNA and guinea pig maximization studies performed on Lanolin alcohol. These unpublished results were generated as part of method validation studies and generally performed under GLP. Further animal studies are not considered required due to the high quality of the studies referred to in the ICCVAM report and for animal welfare reasons. A QSAR using the DEREK software was performed on 3 structures representing molecules found in Lanolin alcohol. This analysis supported a non-sensitization potential of Lanolin alcohol.

 

Finally, there is a long historic use of Lanolin and a significant exposure - from infant to advanced age - with no major reports of adverse effects. The available patch-test studies have mostly been performed with concentrated Lanolin alcohol fractions on subjects diagnosed with various types of dermatitis and hypersensitivity most likely unrelated to prior Lanolin exposure. Accordingly, they do not reflect the general population. Even in these study populations there was a relatively low incidence of an allergic reaction to Lanolin alcohols. According to EU Regulation 1272/2008 (CLP/GHS), classification as a Category 1 skin sensitizer (H317) is dependent to the following criteria:

 

(i) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons, or

(ii) if there are positive results from an appropriate animal test (see specific criteria in paragraph 3.4.2.2.4.1).

 

The available patch-test results do not support that exposure to Lanolin alcohol will lead to skin sensitization in a “substantial number of persons”. It can not be excluded that a very low level (significantly lower than the estimates based on patch-testing) of individuals might develop skin sensitization to Lanolin alcohols due to increased sensitivity or pre-existing conditions. However, this should be considered a normal population reaction and is observed with many chemicals not classified for skin sensitization.


In conclusion, a weight-of-evidence evaluation of the available literature does not support a classification for skin sensitization of Lanolin alcohols. This is supported by animal studies referred to in an ICCVAM report and a QSAR evaluation.