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

Endpoint summary

Description of key information

There are no toxicokinetic studies that have directly addressed the absorption, distribution, metabolism, or excretion of Distilled Grade. However, information on these processes have been inferred based upon the properties of the chemical and the results of reliable and relevant short- and longer-term mammalian toxicity tests based on guidance given in ECHA (2017).

Based on the lipophilicity of the different forms of cardanol (estimated log Kow values >8.31for all forms) and their molecular weights (298 to 304 g/mole), the expected rate of transfer of substances between the stratum corneum and the epidermis (which is resistant to penetration by highly lipophilic substances) will be slow and will limit absorption across the skin. The systemic toxicity observed in the mammalian studies are indicative to an extent of absorption and distribution of the test substance.

Given the test substances high measured partition coefficient (log Kow of > 6.2), it is expected that the bioavailability of the different constituents for metabolism will be reduced. Based on the low water solubility and a molecular weight of 298 to 304 g/mole, cardanol is more likely that they will be excreted in the bile rather than in urine. The individual BCF values for the four forms of cardanol, measured in an OECD TG 305 Bioaccumulation study (both before and after lipid normalisation), were <2000 L/kg, therefore, no bioaccumulation is expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

100

Additional information

The absorption, distribution, metabolism, and excretion of Distilled Grade, and its key constituents (the different forms of cardanol) has not been directly studied in vivo. However, information on these processes have been inferred based upon the properties of the chemical and the results of reliable and relevant short- and longer-term mammalian toxicity tests based on guidance given in ECHA (2017).

The only likely route of absorption of the different forms of cardanol in Distilled Grade is through the dermal route due to the industrial use patterns of the test substance identified in the Risk Characterisation Exercise. However, the high octanol-water partition coefficients of the different forms of cardanol and their molecular weights along with data from an Acute Dermal Toxicity Study (OECD TG402) indicate that limited absorption via the skin is likely. The irritancy of the test substance may affect the permeability of the skin barrier. Mammalian toxicity studies using oral gavage show that the constituents can cross the gastrointestinal tract resulting in systemic distribution. The substance's low vapour pressure means the different constituents will not be present as an aerosol or vapour in the substances normal use pattern. Thus exposures via inhalation that lead to absorption through the respiratory system are unlikely given that the substance is unlikely to be inhaled.

Data from oral gavage mammalian toxicity studies have shown that absorbed constituents of Distilled Grade can be distributed in the body after absorption based on observed effects. However, it appears that the test substance probably does not cross the placental barrier. Given the physico-chemical properties of the different constituents of Distilled Grade it is expected that bioavailability for metabolism will be reduced and they will be excreted in the bile rather than in the urine.