Registration Dossier

Administrative data

Description of key information

In a primary dermal irritation study, 3 young adult New Zealand white rabbits were dermally exposed to read across substance 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, Distilled Grade  is a dermal irritant. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated, Distillation Residue (Distilled Residue 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 applicaiton. 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.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Results recorded at 24 and 72 hours only.
Qualifier:
according to
Guideline:
other: FHSA standard 16 CFR 1500.41
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs
- Age at study initiation: Young adult
- Weight at study initiation: 2.1 - 2.7 kg
- Housing: 1/cage in suspended cages
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
1 male/ 2 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: Plastic


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle wiping

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Remarks:
Sample 1500-1, animal 1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Sample 1500-1, animals 2 and 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1500-1, animal 1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1500-1, animals 2 and 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Sample AF6155, animals 1, 2 and 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample AF6155, animal 1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample AF6155, animal 2
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample AF6155, animal 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Sample 1600-1, animals 1, 2 and 3
Basis:
mean
Time point:
other: 24 and 72
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1600-1, animal 1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0.5
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1600-1, animal 2
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1600-1, animal 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Sample 1650-1, animals 1 and 3
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
Sample 1650-1, animal 2
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1650-1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
Sample 1650-1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
Sample 1650-1
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.5
Max. score:
2
Reversibility:
not fully reversible within: 72 hours

Read across justification

The read across substance is Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”). The study for distilled grade is considered relevant for read across to distillation residue grade since the two substances:

•Contain the same constituents (cardanol, cardol, 2-methyl cardol, C13 and unidentified phenolics, C17 phenolics and polymeric species), generally in similar proportions.

•Have similar physico-chemical properties in terms of their water solubility, vapour pressure and octanol-water partition coefficient.

Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) has a higher proportion of lower molecular weight, more potentially toxicologically active components, (principally cardanol) and lower proportion of more inert polymeric species compared to Distillation Residue Grade. The relative typical proportions of the cardanol and polymeric species in Distilled and Distillation Residue Grades are 78% versus 35% and 2% versus 50% respectively. Therefore, it is considered that distilled grade has the potential to exert greater toxicity within the group of distilled, technical and distilled residue grades (see Section 3.1 - Technological Process) for endpoints relevant to human health and environmental effects. On this basis within the group of distilled, technical and distilled residue grades, the substance Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled represents the potentially most (eco)toxicologically active form.

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Samples 1500-1 and AF6155 were irritating, however, samples 1600-1 and 1650-1 were not irritating.
Executive summary:

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation
Remarks:
in vitro
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD guidelines and to GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml
Duration of treatment / exposure:
10 seconds
Observation period (in vivo):
pre-enucleation, post equilibration and 60, 120, 180, and 240 minutes following treatment.
Number of animals or in vitro replicates:
In vitro - 3 eyes and 2 control eyes.
Details on study design:
It is a legal and ethical duty under the Animals (Scientific Procedure) Act 1986 that in the interest of animal welfare, the unnecessary use of animals is avoided, and that any testing which is likely to produce severe responses in animals is minimised.
Available informaiton indicated that the test material had the potential to produce severe effects in a rabbit eye and to confirm this initial assessment, a Rabbit Enucleated Eye Test was performed.
A study was performed to assess the ocular irritancy potential of the Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) in the rabbit following application onto the cornea of the enucleated eye. The assay has undergone inter-laboratory validation and has been shown to reliably detect test materials that are negligible, or moderate to severe ocular irritants.
The New Zealand White strain rabbit used in these laboratories has been shown to produce satisfactory responses using known ocular-irritants and non-ocular irritants during in-house validation. The results of the study are believed to be of value in predicting the ocular irritancy potential of the test material in man.
Irritant / corrosive response data:
The data for all endpoints was assessed and an estimate of the test material ocular irritancy potential was made based on the following cut-off values:

REET Parameter REET cut-off value
Maximum Corneal Opacity > = 4
Maximum fluorescein uptake > = 4
Mean corneal swelling > = 25%
Corneal epithelium observations Any pitting, mottling or sloughing

Read across justification

The read across substance is Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”). The study for distilled grade is considered relevant for read across to distillation residue grade since the two substances:

•Contain the same constituents (cardanol, cardol, 2-methyl cardol, C13 and unidentified phenolics, C17 phenolics and polymeric species), generally in similar proportions.

•Have similar physico-chemical properties in terms of their water solubility, vapour pressure and octanol-water partition coefficient.

Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) has a higher proportion of lower molecular weight, more potentially toxicologically active components, (principally cardanol) and lower proportion of more inert polymeric species compared to Distillation Residue Grade. The relative typical proportions of the cardanol and polymeric species in Distilled and Distillation Residue Grades are 78% versus 35% and 2% versus 50% respectively. Therefore, it is considered that distilled grade has the potential to exert greater toxicity within the group of distilled, technical and distilled residue grades (see Section 3.1 - Technological Process) for endpoints relevant to human health and environmental effects. On this basis within the group of distilled, technical and distilled residue grades, the substance Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled represents the potentially most (eco)toxicologically active form.

Moderate loss of transparency was noted in all test eyes during the study.

Corneal swelling of the test eyes was considerably greater than that observed in the control eyes over the same period.

Pitting and sloughing of the corneal epithelium was noted in all test eyes during the study.

Moderate fluorescein uptake was noted in the test eyes 240 minutes following test material applicaiton. No fluorescein uptake was noted in the control eyes 240 minutes following treatment.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) causes severe irritation to eyes. A similar conclusion is expected for Cashew Nutshell Extract, Decarboxylated, Distillation Residue (Distilled Residue Grade).
Executive summary:

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.

 

Severe eye 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, Distillation Residue (Distilled Residue Grade).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is irritating to skin and severly irritating to the eyes.

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 “Distillation Residue Grade”) is attached in the endpoint summary.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

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, Distillation Residue (Distilled Residue Grade) based on the read-across justification.