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 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. 
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.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: FHSA standard 16 CFR 1500.41
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
72 h
Score:
> 4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
24 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Sample 1500-1
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Sample 1500-1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Sample 1500-1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Remarks on result:
not measured/tested
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: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted to OECD guidelines and to GLP.
Qualifier:
according to guideline
Guideline:
other: Rabbit Enucleated Eye Test
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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 information 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 test material 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.
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #1 60 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #1 120 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #1 180 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #1 240 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #2 60 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #2 120 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #2 180 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #2 240 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #3 60 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #3 120 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #3 180 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
cornea opacity score
Run / experiment:
Test eye #3 240 minutes
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1 60 minutes
Value:
12.7
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1 120 minutes
Value:
26.2
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1 180 minutes
Value:
39.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #1 240 minutes
Value:
69.6
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2 60 minutes
Value:
12.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2 120 minutes
Value:
23.5
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2 180 minutes
Value:
43.8
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #2 240 minutes
Value:
51.4
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3 60 minutes
Value:
16.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3 120 minutes
Value:
27.3
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3 180 minutes
Value:
53.6
Vehicle controls validity:
valid
Irritation parameter:
percent corneal swelling
Run / experiment:
Chamber #3 240 monutes
Value:
73.5
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test eye #1
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test eye #2
Value:
> 8
Vehicle controls validity:
valid
Irritation parameter:
fluorescein retention score
Run / experiment:
Test eye #3
Value:
> 8
Vehicle controls validity:
valid

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.
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.

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 severely irritating to the eyes.

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.