No IUPAC name is currently defined for Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated (Technical Grade).

Endpoint summary

Description of key information

In a primary dermal irritation study, 3 young adult New Zealand white rabbits were dermally exposed to Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) for 24 hours. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. In this study, Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a dermal irritant. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification. 
In a rabbit enucleated eye study 0.1 ml of Cashew Nutshell Extract, Decarboxylated, Distilled (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. An in vivo eye irritation study is not required.  A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

 

 

To provide data on the skin irritation of Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated (Technical Grade) an OECD TG 439 study (In Vitro Skin Irritation Reconstructed Human Epidermis Test Method) has been conducted on all three grades. However, inconclusive outcomes were recorded for all three grades due to the nature of the test substances (i.e. they were oily viscous liquids which caused staining). These primarily related to difficulties in removing the test substances from the viable tissues without causing superficial damage and also to the fact that the test substances that remained on the tissues affected the test measurements. These issues are likely to have affected the reliability of the results and the interpretation of the data with regard to a substances’ potential to cause skin irritation.

No further assessments of skin irritation/corrosion data have been made for Technical Grade (and Distillation Residue Grade) because it was not considered appropriate from an animal welfare standpoint. It is a legal and ethical duty under the Animals (Scientific Procedure) Act 1986 that the unnecessary use of animals is avoided, and that any testing which is likely to produce severe responses in animals is minimised. There is evidence that Distilled Grade is an skin irritant (see 7.3.1)  in a previous primary dermal irritation study (FHSA Standard 16 CFR 1500.41), three young adult New Zealand white rabbits were exposed dermally to Distilled Grade for 24 hours. Animals then were observed for 72 hours and irritation was scored by the method of Draize. A similar conclusion is expected for Technical Grade (and Distillation Residue Grade) since it is postulated that the effects are due to cardol which is present in all the grades of processed cashew nutshell extract at concentrations of 5 to 13%.  Studies by Keil et al. (1947), Schwartz et al. (1957), Rosen and Fordice (1994) and Diogenes et al. (1995, 1996) indicate that cardol is considered to act as a skin and eye irritant when present above threshold concentrations (of 1 to 2%). This is because the different forms of the substance share a common molecular skeleton with forms of urushiol an oily organic allergen found in plants of the family Anacardiaceae especially Toxicodendron spp. (e.g. poison oak, poison ivy, poison sumac) or Anacardium occidentale (Cashew Nut tree). Given that the three grades are considered to be skin irritants a further skin irritation/corrosion test for Technical Grade has not been conducted and relevant data has been generated by read-across from the source substances Distilled Grade and Distillation Residue Grade.

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 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 the Technical Grade. On this basis Technical Grade is considered to be a skin irritant.

 

References

 

Dióegenes, M.J.N., Morais, S.M.D.E and Carvalho, F.F. (1995) Perioral Contact Dermatitis by Cardol. International Journal of Dermatology, 34(1), 72-73.

Dióegenes, M.J.N., Morais, S.M.D.E. and Carvalho, F.F. (1996) Contact Dermatitis among Cashew Nut Workers. Contact Dermatitis, 35(2), 114-115.

Keil, H., Wasserman, D. and Dawson, D.R. (1945) The relation of hypersensitivity to poison ivy and to the pure ingredients in cashew nut shell liquid and related substances. Industrial Medicine and Surgery, 14, 825-830.

Rosen, T. and Fordice, D.B. (1994) Cashew Nut Dermatitis. Southern Medical Journal, 87(4), 543-546.

Scharwtz, L. Tulipan, L. and Peck, S.M. (1957) Occupational Disease of the Skin, 2nd Edition. Lea and Febiger Publishers, Philadelphia, pp638-647.

Justification for classification or non-classification

Skin irritation was observed.  In this study, Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a severe eye irritant.

A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated (Technical Grade) based on the read-across justification.