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Description of key information

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Skin sensitisation

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Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was already available from 1995.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, UK
- Weight at study initiation: 328 to 455 g
- Housing: Solid floor polypropylene cages
- Diet (e.g. ad libitum): Guinea pig FD1 diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 44-64%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
1% induction, 5% and 2% challenge
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
1% induction, 5% and 2% challenge
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Day 1, intradermal injection; day 7, occlusive topical application for 48 hours
- Concentrations: 1% intradermal injection, 25% topical application


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Site: clipped right flank
- Concentrations: 5% and 2%
- Evaluation (hr after challenge): 24 and 48 hours after challenge removal
Positive control substance(s):
yes
Remarks:
Poison ivy oil
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 14.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
8
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2%. No with. + reactions: 8.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1%
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1%. No with. + reactions: 20.0. Total no. in groups: 20.0.
Group:
negative control
Remarks on result:
not measured/tested
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a dermal sensitisation study with cashew nutshell liquid (distilled grade sample), guinea pigs (20) were tested with in a guinea pig maximisation test.

In this study, Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a dermal sensitiser.
Executive summary:

Positive reactions in 30% of test animals is required for a positive sensitising result in an adjuvant test. A positive response was elicited in 70% of animals when adminsitered 1% induction and challenged with a 5% concentration. Greater than 60% of animals responded at a 1% intradermal induction dose, therefore sub-category 1A is appropriate.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In a dermal sensitisation study with Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade), guinea pigs (20) were tested with in a guinea pig maximisation test. Positive reactions in 30% of test animals is required for a positive sensitising result in an adjuvant test. A positive response was elicited in 70% of animals when a 1% induction dose was applied and challenged with a 5% concentration. Therefore, according to guidelines, this substance is a sensitiser. Greater than 60% of animals responded at a 1% intradermal induction dose, therefore sub-category 1A is appropriate. In a dermal sensitisation study with distilled Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) in acetone/olive oil 4:1, four young adult CBA mice were tested using the LLNA method.  Mild redness to the eyes and neck were observed in test animals. No other clinical signs of toxicity were noted and mortality did not occur. Bodyweights of treated animals were comparable to that of controls. Stimulation indexes of 29.29 and 30.90 were identified, for NX-4708 and NX-2023, respectively.  In this study, distilled Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a dermal sensitiser.

EC3 value was not directly determined, however, 10% of test substance elicited a stimulation index of 30 (EC3 = % test substance required to elicit a stimulation index of 3).

The two studies indicate that Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a skin sensitiser category 1A.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a guinea pig maximisation test, positive response was elicited in 70% of animals when a 1% induction dose was applied, and challenged with a 5% concentration. Therefore, according to guidelines, this substance is a dermal sensitiser. Greater than 60% of animals responded at a 1% intradermal induction dose, therefore sub-category 1A is appropriate.

In a LLNA, Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) gave stimulation indexes of 29.29 and 30.90 following administration of 10% dose, therefore is classed as a dermal sensitiser. The EC3 value was not directly determined, however, 10% of test substance elicited a stimulation index of 30 (EC3 = % test substance required to elicit a stimulation index of 3).

The two studies indicate that Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is a skin sensitiser category 1A.