Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
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 eye irritation in vivo endpoint no test data is available for the registered substance Distillation Residue 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 rabbit enucleated eye study 0.1 ml of Distilled Grade was instilled into three eyes of New Zealand White rabbits. The eyes were observed for 240 minutes. Irritation was scored by the method of McDonald-Shadduck. Moderate fluorescein uptake was noted in the test eyes 240 minutes following test material application. No fluorescein uptake was noted in the control eyes 240 minutes following treatment. Following assessment of the data for all endpoints, the test material was considered to have the potential to cause ocular irritancy in vivo and an in vivo eye irritation study was not required. It is considered appropriate to read-across from the data for Distilled Grade to Distillation Residue Grade with the result that it has been estimated that an eye irritation test in vivo is not required for Distillation Residue Grade given its potential to cause ocular irritancy.

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): Cashew Nutshell Liquid (CNSL) Distilled (Distilled grade)
- Lot/batch No.: ME-0163
- Other: Dark amber coloured liquid

Results and discussion

In vitro

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #1, 60 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #1, 120 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #1, 180 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #1, 240 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #2, 60 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #2, 120 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #2, 180 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #2, 240 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #3, 60 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #3, 120 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #3, 180 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test Eye #3, 240 mins
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1, 60 mins
Value:
12.7
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1, 120 mins
Value:
26.2
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1, 180 mins
Value:
39.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1, 240 mins
Value:
69.6
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2, 60 mins
Value:
12.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2, 120 mins
Value:
23.5
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2, 180 mins
Value:
43.8
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2, 240 mins
Value:
51.4
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3, 60 mins
Value:
16.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3, 120 mins
Value:
27.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3, 180 mins
Value:
53.6
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3, 240 mins
Value:
73.5
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test Eye #1
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test Eye #2
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test Eye #3
Value:
> 8
Vehicle controls validity:
valid
Other effects / acceptance of results:
The data for all endpoints was assessed and an estimate of the test material ocular irritancy potential was made based on the following cut off values:

REET Parameter REET Cut off value
Maximum Corneal Opacity (Corneal Cloudiness x Area) > or = 4
Maximum Fluorescein Uptake (Intensity x Area) > or = 4
Mean Corneal Swelling (mins) 60,120,240 > or = 25%
Corneal Epithelium Observations Any with pitting, motting or slouhing

Pitting and sloughing of the corneal epithelium was noted in all test eyes during the study.

Moderate loss of transparency was noted in all test eyes during the study ie. the value obtained was >4.

Corneal swelling of the test eyes was considerably greater than that observed in the control eyes over the same period.


Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) causes severe irritation to eyes. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated, Technical Grade.
Executive summary:

For the eye 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 rabbit enucleated eye study 0.1 ml of Distilled Grade was instilled into three eyes of New Zealand White rabbits. The eyes were observed for 240 minutes. Irritation was scored by the method of McDonald-Shadduck. Moderate fluorescein uptake was noted in the test eyes 240 minutes following test material application. No fluorescein uptake was noted in the control eyes 240 minutes following treatment. Following assessment of the data for all endpoints, the test material was considered to have the potential to cause ocular irritancy in vivo and an in vivo eye irritation study was not required. 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 an eye irritation test in vivo is not required for Technical Grade given its potential to cause ocular irritancy.