Registration Dossier

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The basis for the adoption of a category approach for the three grades of processed Cashew Nutshell Extract is the commonality of the constituents and functional groups in the three grades and the common modes of action for specific localised endpoints that are manifest in physico-chemical, environmental fate and toxicological properties that are similar or follow a regular pattern as a result of structural similarity. The ECHA Final Decisions on the Annex IX and X (mammalian toxicology, ecotoxicology and environmental fate) Testing Proposals for three grades confirmed the applicability of a category approach which involves reading data across from the source substances Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) and Cashew Nutshell Extract, Decarboxylated, Distillation Residue (Distillation Residue Grade) to the target substance Cashew Nutshell Extract, Decarboxylated (Technical Grade) by interpolation. In this context interpolation is “the estimation of a value for a member of the group using measured values from other members on both sides of that member within the defined group spectrum”. Further details on the justification for using the interpolation based read-across approach are given in the attached document “Report on the grouping and read-across rationale for the three grades of processed Cashew Nutshell Extract”. The interpolation approach has been applied to the Annex IX OECD TG408 and TG414 testing on Distilled and Distillation Residue Grades. For the Annex VII and VIII endpoints a programme of testing has been carried out to provide comparative information for the three grades and develop a data matrix to support the category and read-across approaches. This has involved generating reliable data for all Annex VII and VIII physico-chemical and environmental fate endpoints and certain mammalian toxicity properties. However, based on the discussions surrounding the Final Decisions it was not considered necessary to apply this approach retrospectively to address all identified data gaps at Annexes VII and VIII. The original data used for the registration of a single substance (Cashew Nutshell Liquid, CAS Number 8007-24-7) was largely based on data for Distilled Grade since this was considered to be the most (eco) toxicologically active form, given the higher content of low molecular weight constituents (such as cardanol) and the low content of polymeric species. Therefore, based on the use of the category approach it is considered appropriate to read-across from the existing short-term mammalian toxicity data for Distilled Grade to the other two grades.
2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
For the skin sensitisation endpoint no test data is available for the registered substance, Technical Grade. However data is available for the compositionally similar substance Distilled Grade which is part of the category of the three grades of CNSL. In a dermal sensitisation study with Distilled Grade, guinea pigs (20) were tested in a guinea pig maximisation test, where positive reactions in 30% of test animals are required for a positive sensitising result in an adjuvant test. A positive response was elicited in 70% of animals when a 1% induction dose was applied and challenged with a 5% concentration. Therefore, according to the guidelines, this substance is a sensitiser. It is considered appropriate to read-across from the data for Distilled Grade to Technical Grade with the result that it has been estimated that the Technical Grade is a dermal sensitiser.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 14.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2%. No with. + reactions: 8.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Group:
negative control
Remarks on result:
not measured/tested

Any other information on results incl. tables

A document which justifies the read–across from Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) and Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distillation Residue (“Distillation Residue Grade”) to Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated (“Technical Grade”) is attached in the Category object

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a dermal sensitization study with cashew nutshell liquid, guinea pigs (20) were tested with in a guinea pig maximisation test.

In this study, Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a dermal sensitizer. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification.
Executive summary:

Positive reactions in 30% of test animals is required for a positive sensitising result in an adjuvant test. A positive response was elicited in 70% of animals when adminsitered 1% induction and challenged with a 5% concentration. Greater than 60% of animals responded at a 1% intradermal induction dose, therefore sub-category 1A is appropriate. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification.