Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
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 irritation in vivo 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 primary dermal irritation study, 3 young adult New Zealand white rabbits were dermally exposed to Distilled Grade for 24 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize and Distilled Grade was characterised as a dermal irritant. 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 Technical Grade will result in skin irritation in vivo.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Distilled CNSL
- Lot/batch No.: 1500-1, AF6155, 100-1, 1650-1

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Sample 1500-01
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
irritating
Conclusions:
In a primary dermal irritation study, 3 young adult New Zealand white rabbits were dermally exposed to Distilled Grade for 24 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize and Distilled Grade was characterised as a dermal irritant. 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 Technical Grade will result in skin irritation in vivo.
Executive summary:

For the skin irritation in vivo 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 primary dermal irritation study, 3 young adult New Zealand white rabbits were dermally exposed to Distilled Grade for 24 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize and Distilled Grade was characterised as a dermal irritant. 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 Technical Grade will result in skin irritation in vivo.