Registration Dossier

Administrative data

Description of key information

Modern, guideline and GLP-compliant studies are available for skin and eye irritation.

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
Study period:
11 October 1993 to 22 November 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline line compliant, GLP study conducted at reputable laboratory.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd
- Age at study initiation: 13-15 weeks old
- Weight at study initiation: 3.1 to 3.5 kg
- Housing: individually in plastic cages with perforated flooring
- Diet (e.g. ad libitum): SDDS Stanrab (P) Rabbit diet ad libitum
- Water (e.g. ad libitum): ad libitum access to tap water
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 October 1993 To: 23 October 1993
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL to one intact site per rabbit
Duration of treatment / exposure:
Four hours
Observation period:
13 days after application of test material
Number of animals:
Three
Details on study design:
TEST SITE
- Area of exposure: 25 x 25 mm

- Type of wrap if used: gauze pad covered by elastoplast elastic adhesive tape to provide semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water and blotting dry
- Time after start of exposure: 4 hours

SCORING SYSTEM: Standard Draize assessment. Rabbit skin was assessed approximately 60 minutes after removal of the treatment dressing and then on Days 2, 3, 4 (24, 48 and 72 hour assessments) and daily from day 5 to 13.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: Generally moderate erythema persisted from Day 1 to day 6 in all three rabbits, ameliorating subsequently and overtly resolved by Day 9 or 13.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 9-11 days
Irritant / corrosive response data:
All three rabbits developed well-defined erythema and slight oedema that persisted from the initial assessment to Day 6 (moderate oedema was recorded on a single occasion for one rabbit, Day 4, but the response was atypical). Slight or very slight reactions persisted with evidence of desquamation over the following week and all reactions had resolved by Day 9 (one rabbit) or Day 13 (two rabbits).
The overall response with means of 2.0 or greater for both erythema and oedema indicated potential for skin irritancy.

Irritation scores (individual animals)

 

1h

24h

48h

72h

Mean (24-72h)

4d

5d

6d

7d

8d

9d

10d

11d

12d

13d

Erythema

2,2,2

2,2,2

2,2,2

2,2,2

2.00 

2,2,2

2,2,2

2,2,2

1,2,2

1,2,2

0,2,2

1,1

1,1

1,1

0,0

Oedema

2,2,2

2,2,2

2,2,2

2,2,2

 2.00

2,2,2

2,2,2

2,2,2

1,1,1

1,1,1

0,1,1

1,1

0,0

0,0

0,0

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The results of this study indicate skin irritation but are not sufficient to trigger classification for skin irritation according to the CLP Regulation.
Executive summary:

In a standard three rabbit assessment of dermal irritation, following 4 hour exposure of intact skin under semi-occluded conditions, slight to well-defined oedema and erythema were observed in all three rabbits, reactions persisted for up to 12 days after application but reversibility was confirmed by Day 13. The results of this study do not trigger classification for skin irritation according to the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 October 1993 to 11 January 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline compliant GLP study conducted at reputable laboratory
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd and/or Froxfield UK Ltd
- Age at study initiation: 13-17 weeks
- Weight at study initiation: 2.8 to 3.9 kg
- Housing: individually in plastic cages with perforated floors
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet ad libitum
- Water (e.g. ad libitum): adlibitum access to tap water
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30-70
- Air changes (per hr):19
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 October 1993 To: 1 November 1993
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL of undiluted amyl cinamic aldehyde instilled into one eye of each rabbit
Duration of treatment / exposure:
The eyelids were held together for one second following instillation to prevent immediate removal of test material. The eyes were not subsequently rinsed or flushed with water, saline or fluorescein.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
three
Details on study design:
The contralateral eye of each rabbit was left untreated as the control for comparative purposes.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
4
Reversibility:
other: no reactions observed
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
2
Reversibility:
other: no reactions observed
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.44
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Slight conjunctival redness and swelling observed an hour after instillation in all three rabbits had largely resolved within 24 hours, very slight conjunctival redness remaining, and all reactions had overtly resolved by Day 2.

The mean scores for reactions over the 24 -72 hour post-instillation period were less than the EU classification thresholds for corneal, iridial and conjunctival responses.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Slight conjunctivitis was elicted by instillation of amyl cinnamic aldehyde into rabbit eyes. No corneal or iridial reactions were observed and the conjunctivae were overtly normal within 48 hours of treatment.
Executive summary:

Instillation of amyl cinnamic aldehyde into the eyes of three rabbits according to standard test methods resulted in only slight transient conjunctival irritation and no corneal or iris reactions. The group mean scores were lower than the classification thresholds and amyl cinnamic aldehyde is therefore not considered for classification as an eye irritant according to CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A modern, guideline and GLP-compliant rabbit study shows some evidence of skin irritation; however the reactions are not sufficient to trigger classification according to CLP criteria.

Eye irritation

A modern, guideline and GLP-compliant rabbit study shows mild and transient eye irritation. Ocular reactions are not sufficient to trigger classification according to CLP criteria.

Justification for selection of skin irritation / corrosion endpoint:

Only one study available for this endpoint.

Justification for selection of eye irritation endpoint:

Only one study available for this endpoint.

Justification for classification or non-classification

The results of skin and eye irritation studies performed with amyl cinnamic aldehyde do not trigger classification for irritation according to the CLP Regulation. A modern, guideline and GLP-compliant rabbit study shows some evidence of skin irritation; however the reactions are not sufficient to trigger classification according to CLP criteria. A modern, guideline and GLP-compliant rabbit study shows mild and transient eye irritation. Ocular reactions are not sufficient to trigger classification according to CLP criteria.