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Toxicological information

Carcinogenicity

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Description of key information

A carcinogenicity study has not been proposed as it may be waived under the specific rules for adaptation to testing.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A carcinogenicity study has not been proposed for Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) because it does not have a widespread dispersive use nor is there evidence of frequent long-term human exposure; and

 

The substance is not classified as mutagen category 3 nor is there evidence from a 28 -day study that the substance is able to induce hyperplasia and/or neoplastic lesions. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification.

Read across justification

Under Annex XI of the REACH Regulation “General rules for adaptation of the standard testing regime set out in Annexes VII to X”, in addition to the specific rules set out in Column 2 of Annexes VII to X, a registrant may adapt the standard testing regime in accordance with the general rules set out in Section 1 of the Annex. One approach that may be used is the grouping of substances and the read-across approach (Section 1.5 of Annex XI). An overall grouping and read-across rationale has been developed for the three grades of cashew nutshell extract. This has involved using data for two source substances Distilled and Distillation Residue grades to read-across the required data for 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”.

The justification for the read-across approach results from 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. Further details on the justification for using the interpolation based read-across approach are given in the accompanying document “Report on the development of an updated grouping and read-across rationale for the three grades of processed Cashew Nutshell extract”. The following points are relevant:

•       The three grades are manufactured using a common process in which the unprocessed cashew nutshell extract is heated, which produces Technical grade. Subsequent distillation does not result in the formation of any new constituents in the resulting Distilled and Distillation Residue grades, but rather changes in the proportion of certain constituents relative to those present in Technical grade.

•       In all the three grades the proportions of three out of the five key constituents namely the low boilers, C17 phenolics and high boilers (cardol and 2-methylcardol) are similar. Whilst the lightest, lower molecular weight non-polymeric constituents (such as cardanol) and the highest molecular weight polymeric constituents vary between the grades, Technical grade compositionally lies between Distilled and Distillation Residue grades.

•       For all the physico-chemical parameters for which measured data are available (relative density, vapour pressure, water solubility, octanol-water partition coefficient, flash point and flammability) the values estimated for the target substance Technical grade from the results generated in tests on the source substances Distilled and Distillation Residue grade are consistent with the actual measured values for Technical grade. The consistency of the estimated and measured values for these endpoints for Technical grade indicate that the read-across approach is appropriate and that reliable results can be generated by interpolation from the source substances (Distilled and Distillation Residue grades). In particular, there is consistency for the key physico-chemical parameters which influence toxicological behaviour of the three grades of processed cashew nutshell extract, namely: water solubility, octanol-water partition coefficient (logKow) and vapour pressure.

•       Based on mammalian toxicity studies conducted with Distilled grade, the following points can be concluded regarding the substance. Systemic effects following repeated dosing indicate that Distilled grade is absorbed via the gastro-intestinal tract. The rate and extent of absorption cannot be elucidated from the data available. Only local effects were observed from an acute dermal toxicity study, and also a skin irritation and sensitisation studies. It is likely that the skin barrier will be compromised by the irritation/sensitisation observed following application of Distilled grade, and that some absorption via this route will occur. Systemic effects in the lung, mesenteric lymph nodes, stomach and duodenum were observed, indicating that Distilled grade is distributed throughout the body, however, the extent of such distribution is unknown. There is no data available regarding metabolism or excretion of the Distilled grade.

The conclusions discussed above suggest similar local and systemic toxicity profiles for all the three substances. The use of data from two source substances (Distilled and Distillation Residue grades) to read-across to Technical grade is considered to provide greater confidence in the predicted data for the target substance, as testing at the two ends of the compositional spectrum will reveal the toxicity or lack of toxicity of all the key constituents (including those of their degradation products) which are present in Technical grade.

Justification for classification or non-classification

Cashew Nutshell Extract, Decarboxylated (Technical Grade) will not be classified for carcinogenicity as genotoxicity studies for the read across substance Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled are negative, neoplastic lesions or hyperplasia have not been identified in repested-dose studies, and a carcinogenicity study is not required.