Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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 acute dermal toxicity 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 an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of Distilled Grade at 2000 mg/kg bw and observed for 14 days. Deaths did not occur in this study, therefore, it can be determined that Distilled Grade is of low acute dermal toxicity. Severe skin reactions were observed in all animals at the test substance application site. 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 will result in low acute dermal toxicity.


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)
- Physical state: Dark amber liquid
- Lot/batch No.: ME-0163
- Storage condition of test material: Stored in the dark at room temperature

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Deaths did not occur during the study.
Clinical signs:
Systemic toxicity was not observed.
Body weight:
Three females showed bodyweight decrease or no gain in bodyweight during the first week with expected gain in bodyweight during the second week. One female showed expected gain in bodyweight during the first week with bodyweight decrease during the second week. All males and one female showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted.
Other findings:
Very slight or well-defined erythema was noted at the test sites of all animals. Other signs of dermal irritation noted were thickening of the skin, haemorrhage of dermal capillaries, hardened light brown or dark brown/black coloured scab, small superficial scattered scabs, scab undulating, scab cracking and scab lifting at edges to reveal bleeding, dried blood, glossy skin or further deep scabbing. Adverse reactions prevented accurate evaluation of erythema and oedema at all test sites during the study.

Any other information on results incl. tables

Table 2: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

 

Dose
(mg/kg bw)

Conc.
in vehicle (%)*

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#/total)

Male

Female

Combined

Male

Female

Combined

2000

 

 0/5

 0/5

0/10 

 -

 5/5

 5/5

10/10

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Deaths did not occur in an acute dermal toxicity test in rats at 2000 mg/kg bw, therefore Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is of low acute dermal toxicity. Severe skin reactions were observed in all animals at the test substance application site.
Executive summary:

In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) at 2000 mg/kg bw and observed for 14 days.

No mortality occurred in this limit test, therefore an LD50 has not been determined.

This acute study is classified as acceptable. It satisfies the guideline requirement for an acute dermal study in the rat.