Registration Dossier

Administrative data

Description of key information

Information from the repeat dose and reproductive toxicity screening test on the read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade)demonstrate low sub-acute oral toxicity and can be used to infer low acute toxicity. In the combined repeated dose/reproductive toxicity screening test, serious adverse effects are not observed with oral dietary doses of up to 1000 mg/kg bw/day, following dosing for 54 consecutive days. On this basis it was not considered appropriate to test for acute oral toxicity, as absence of severe adverse effects at this dose following repeated dosing indicates that mortality is unlikely to occur after a single dose in an acute oral toxicity test at doses that would trigger classification. A limit dose test of 2000 mg/kg bw/day can be waived, as no further information on hazard class would be generated. Limit tests are usually required by regulatory regimes when a substance is not expected to be toxic. However, REACH allows for waiving of tests where the hazard and risk of a substance can be inferred by alternative means. Expert judgement can, therefore, be exercised to waive the acute oral toxicity test, based on a weight of evidence approach. In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (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 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. Exposure of humans to Cashew Nutshell Extract, Decarboxylated, (Distillation Residue Grade) via inhalation is not likely, taking into account the vapour pressure of the substance and the low possibility of exposure to aerosols, particles or droplets of an inhalable size.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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 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 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 Distillation Residue Grade with the result that it has been estimated that Distillation Residue Grade will result in low acute dermal toxicity.
Test type:
standard acute method
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
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. 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 Distillation Residue Grade will result in low acute dermal toxicity.
Executive summary:

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

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 Distillation Residue Grade will result in low acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

For the assessment of acute toxicity the read across substance is Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”).

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

Justification for classification or non-classification

An LD50 of >2000 mg/kg bw was idenitified from an acute dermal toxicity study, therefore read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is of low acute dermal toxicity and does not warrant classification under the DSD. However, classification with category 4, harmful in contact with skin, is appropriate under CLP.

Inflammation from a sub-acute repeat dose toxicity combined screening test infers that effects do not occur at doses up to 1000 mg/kg bw/day, therefore, classification is not warranted under the DSD. However, classification with category 4, harmful in contact with skin, is appropriate under CLP.

No data are available to classify the acute inhalation effects.