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Diss Factsheets
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EC number: 941-212-1 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- other: Expert review and assessment derived from available information
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 2 020
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Expert review of available data
- GLP compliance:
- no
Test material
- Reference substance name:
- No IUPAC name is currently defined for Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distillation Residue (Distillation Residue Grade).
- EC Number:
- 941-212-1
- Molecular formula:
- Cardanol (saturated side chain): Formula: C21 H36 O Cardanol (monoene): Formula: C21 H34 O Cardanol (diene): Formula: C21 H32 O Cardanol (triene): Formula: C21 H30 O
- IUPAC Name:
- No IUPAC name is currently defined for Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distillation Residue (Distillation Residue Grade).
Constituent 1
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Absorbed via the gastro-intestinal tract (rate and extent of absorption cannot be elucidated from the data available)
- Type:
- absorption
- Results:
- Adsorbed to a limited degree across the skin barrier (rate and extent of absorption cannot be elucidated from the data available). The irritancy of the test substance may affect the permeability of the skin barrier.
Any other information on results incl. tables
There are no toxicokinetic studies that have directly addressed the absorption, distribution, metabolism, or excretion of Distillation Residue Grade, which is a UVCB with the main components (comprising ~85% of content) being the four forms of the alkylphenol cardanol (i.e. the monoene, diene, triene and saturated side chain) and larger size, higher molecular weight polymeric constituents. Other alkylphenols (such as cardol and methylcardol) are present at lower levels. 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).
Systemic availability of the different forms of cardanol depends on their ability to cross biologibal membranes be absorbed across body surfaces (such as the skin, the gastrointestinal tract and the respiratory tract epithelium of the lungs). Physico-chemical parameters that affect toxicokinetic processes include water solubility, lipophilicity (characterized by the log of the octanol-water partition coefficient, log Kow), degree of ionization (as defined by the dissociation constant, pKa), and molecular size. The physical state of Distillation Residue Grade is an oily liquid at ambient temperature which is very lipophilic, with an estimated log Kow of 6.2. Distillation Residue Grade has a low measured water solubility of 0.3 mg/l, but the constituents of the test substance are not readily ionisable.
Absorption: The only likely route of absorption of the different constituents of Distillation Residue Grade is via dermal exposure due to the typical industrial use patterns of the test substance identified in the exposure scenarios given in the Risk Characterisation Exercise. However, the lipophilicity of the different forms of cardanol (estimated log Kow values > 8.31 for all forms) and their molecular weights (298 to 304 g/mole) means that the expected rate of transfer of substances between the stratum corneum (the non-viable layer of corneocytes forming a complex lipid membrane that must be first penetrated) and the epidermis (which is resistant to penetration by highly lipophilic substances) will be slow and will limit absorption across the skin. In addition uptake of the Distillation Residue Grade constituents into the stratum corneum itself may also be slow unless any damage to the skin surface caused by the substance (an identified irritant) enhances penetration (ECHA, 2017). Distillation Residue Grade also contains a high proportion of larger size and higher molecular weight polymeric constituents which are expected to have more limited absorption through the skin than the different forms of cardanol. Evidence for limited skin absorption is provided by an Acute Dermal Toxicity study (OECD TG402) on another grade of CNSL (Distilled Grade) where Wistar rats that were exposed to a single dose of 2000 mg/ kg body weight for 24 hours showed no signs of systemic toxicity throughout the 14-day observation period. Signs of systemic toxicity would be an indication that absorption has occurred. At the end of the test all animals were subjected to an external examination and opening of the abdominal and thoracic cavities. No abnormalities were noted at necropsy .
Absorption via the oral route of exposure is not likely to occur given the normal use patterns of Distillation Residue Grade. The high log Kow’s and low water solubilities of the different forms of cardanol and the polymeric constituents mean that they would be expected to be poorly absorbed across the gastrointestinal tract unless absorption was enhanced by the process of micellular solubilisation , if this is relevant to the test substance (ECHA, 2017). Repeated dose exposure studies have been conducted using the oral gavage route of exposure since the test substance is classified as a Category 2 Skin Irritant (H315) and it was not considered appropriate from an animal welfare viewpoint to conduct the studies using the dermal route of exposure. The data from a Repeated Dose 90-day Toxicity Study (OECD TG408) showed that there were local adverse histopathological changes in forestomach morphology in exposed rats at the highest test dose (1000 mg/kg bw/day) used in the study. However, these effects were not evident in the pregnant females exposed to a similar high dose of Distillation Residue Grade in a Prenatal Developmental Toxicity Study (OECD TG414). These local effects are considered to be due to known irritancy of the test substance and could have affected the absorption of the different constituents of Distillation Residue Grade. Furthermore, in these studies Distillation Residue Grade has been dosed with a vehicle (dried and deacidified corn oil) and the water solubility of the vehicle and the vehicle/water partition coefficient of the vehiclesubstance may affect the rate of uptake (ECHA, 2017).
In the oral exposure studies signs of toxicity can be taken as evidence that absorption has occurred. In the OECD TG408 study, during macroscopic and histopathological examinations of animals at necropsy after 90 days exposure, test substance-related effects were observed in the stomach, liver, mesenteric lymph nodes and thyroid gland. In the liver, minor increases in liver weight were noted in males and females, which may correlate with measured increases in the liver enzymes alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and alkaline phosphatase (ALP) noted in these animals. The effects observed in the liver at the highest test dose were considered to be suggestive of hepatocellular damage and were considered to be adverse. In the mesenteric lymph nodes, erythrophagocytosis was noted in males, which correlated to macroscopic dark discoloration and foci. The effects observed in the mesenteric lymph nodes may be secondary to the changes in the stomach. In the thyroid gland, diffuse follicular cell hypertrophy was noted in males, which was without any degenerative changes. The findings in the mesenteric lymph nodes and thyroid gland were a common background finding, lacked any histopathological correlation or were without any degenerative changes, and therefore were not considered to be adverse. However, they are indicative to an extent of absorption (and distribution) of the test substance. In the OECD TG414 study no maternal toxicity was observed at any of the test doses.
The OECD TG408 and TG414 data sets for Distillation Residue and Distilled Grades of CNSL indicate that Distilled Grade shows greater systemic and local toxicity compared to Distillation Residue Grade in terms of the derived NOAEL values for both systemic toxicity and local toxic effects . The greater comparative toxicity of Distilled Grade indicates that the higher proportion of low molecular weight non-polymeric constituents in this grade were responsible for the effects observed rather than the higher molecular weight polymeric content (which is present in greater levels in Distillation Residue Grade).
Distillation Residue Grade only exists in liquid form and, based on the substance's low vapour pressure (0.00005 Pa at 25oC), the different constituents will not be present as an aerosol or vapour in the substances normal use patterns. Thus exposures via inhalation that lead to absorption through the respiratory system are unlikely given that the substance is unlikely to be inhaled . Furthermore, the different constituents of Distillation Residue Grade are not likely to be absorbed based on their lipophilicity and low water solubility, though uptake via the respiratory tract epithelium could be enhanced by the process of micellular solubilisation (ECHA, 2017).
Distribution: Given the low water solubility of Distillation Residue Grade (and the different forms of cardanol and the polymeric constituents), any absorbed chemical will probably be distributed through the body via the lipids rather than by circulation in the blood. In the OECD TG408 Repeated Dose 90-day Toxicity study the responses, though largely non-adverse, indicated that the different forms of cardanol had been distributed through the rats to the liver, mesenteric lymph nodes and thyroid gland. In the OECD TG414 Prenatal Developmental Toxicity study the absence of any observed effects on the foetuses in the study indicates that the test substance probably does not cross the placental barrier.
Metabolism: 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. The liver is expected to be the primary organ to receive and metabolize the different forms of cardanol, making them more soluble by oxidation and conjugation and releasing the more polar compound into the bile for elimination via the gastrointestinal tract. Any chemical which is not metabolized is expected to be excreted either through the urine or faeces. However, it is recognised that it is difficult to predict the metabolic changes that the different constituents of Distillation Residue Grade may undergo on the basis of physico-chemical information alone (ECHA, 2017).
Excretion: There is no reported data available on the excretion of any absorbed constituents of Distillation Residue Grade. The major routes of excretion for substances from the systemic circulation are the urine and/or the faeces (via the bile and directly from the gastrointestinal mucosa). For constituents such as cardanol, which show low water solubility and a molecular weight of 298 to 304 g/mole, it is more likely that they will be excreted in the bile rather than in urine (ECHA, 2017)
Accumulation potential: Although the high log Kow values for the different forms of cardanol indicate they would be expected to accumulate in the body of organisms, low Bioconcentration Factors (BCFs) values were measured in an OECD TG305 Bioconcentration in Fish study for another grade of CNSL (Distilled Grade). The individual BCF values obtained for the four forms of cardanol, both before and after lipid normalisation, were <2000 L/kg. A BCF of 2000 L/kg is the threshold for a test substance to be considered to be bioaccumulative meaning the different forms of cardanol should not accumulate within the body. It is anticipated that a similar result will be obtained in the test on Distillation Residue Grade given the presence of a significant proportion of larger size, higher molecular weight polymeric constituents that are not expected to bioaccumulate.
Applicant's summary and conclusion
- Conclusions:
- There are no toxicokinetic studies that have directly addressed the absorption, distribution, metabolism, or excretion of Distilation Residue 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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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