Registration Dossier

Administrative data

Description of key information

In vivo skin irritation study in rabbits with benzyl benzoate
In vivo eye irritation study in rabbits with benzyl benzoate

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
Study period:
April 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The restriction is due to the use of the read across approach: the test was performed not with 3-PPB but with Benzyl benzoate, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: A Smith , Warlingham, Surrey
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: individually housed in anodised aluminium caging with grid flooring
- Diet (e.g. ad libitum): Dalgety-Spillers pelleted rabit diet ref. 680 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 42-65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 April 1985 To: 23 April 1985
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL applied to dorsum of each of four rabbits
Duration of treatment / exposure:
4 hour exposure
Observation period:
7 days
Number of animals:
4
Details on study design:
Four rabbits were treated simultaneously with four test materials (two per flank placed distally and caudally on the shaved dorsum). 0.5 mL of undiluted test material was applied to a square of surgical lint whicwas held in situ on the rabbit by means of an encircling elasticated adhesive bandage. The dressing was removed after four hours (treated sites were swabbed with cotton wool and warm water to remove residual material immediately after removal of the dressing) and treated sites assessed after 1, 24, 48, 72 and 168 hours for signs of dermal change that was scored using the standard Draize assessment scheme
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1.2
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
Three of the four treated sites showed evidence of slight erythema within an hour of the dressing removal. For two of these rabbits well defined erythema developed over the following 72 hours with slight reactions remaining for the third rabbit. slight erythema persisted for seven days in one animal but was showing a degree of amelioration over the study time course although not fully resolved by termination. No reactions developed in one rabbit throughout the study.
Very slight oedema was observed for three rabbits but the reactions did not progress in severity and resolved with 48 or 168 hours
Other effects:
None observed

Dermal reactions with benzyl benzoate

Rabbit number

1 hr

24 hr

48 hr

72 hr

168 hr

591

 

 

 

 

 

Erythema
Oedema

0
0

0
0

0
0

0
0

0
0

596

 

 

 

 

 

Erythema
Oedema

1
1

2
1

2
0

1
0

0
0

598

 

 

 

 

 

Erythema
Oedema

1
1

1
1

1
0

1
0

0
0

600

 

 

 

 

 

Erythema
Oedema

1
1

2
1

2
1

2
1

1
0

Mean

 

Erythema = 1.2
Oedema = 0.4

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Generally slight or very slight erythema or oedema was apparent in three of four treated rabbits, with reactions persisting for three days but typically resolved by day 8. Mean scores for erythema and oedema assessed over the 24 to 72 hour assessments were less than 2.0 and did not trigger classification thresholds for benzyl benzoate.
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:
11 to 18 March 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The restriction is due to the use of the read across approach: the test was performed not with 3-PPB but with Benzyl benzoate, a substance which has been demonstrated to be very similar in structure, physical/chemical properties and toxicological profile.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
six rabbits used rather than three, but this does not affect validity of results
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals Scottdale, Pennsylvania
- Age at study initiation: no information
- Weight at study initiation: 2.07 to -2.28 kg (males - 2.066, 2.279 and 2.158 kg; females - 2.144, 2.261 and 2.247 kg)
- Housing: individually in laboratory standard cages
- Diet (e.g. ad libitum): Wayne Rabbit Ration ad libitum
- Water (e.g. ad libitum): Potable tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%):30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 March 1982 To: 18 March 1982
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contralateral eye used as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted, as supplied

Duration of treatment / exposure:
single instillation
Observation period (in vivo):
7 days, treated eyes assessed on day 1, 2, 3, 4 and 8 at 1, 24, 48, and 72 hours post instillation and again after 7 days
Number of animals or in vitro replicates:
6, three males, three females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No reported flushing the treated eyes
- Time after start of exposure: not applicable

SCORING SYSTEM: standard Draize assesment

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein -- no details reported
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: one hour post instillation
Score:
0
Max. score:
80
Reversibility:
other: no effects observed
Remarks on result:
other: No corneal changes noted in six rabbits
Irritation parameter:
iris score
Basis:
mean
Time point:
other: one hour post instillation
Score:
0.83
Max. score:
10
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: only one treated eye showed iridial reaction
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: one hour post instillation
Score:
2.67
Max. score:
20
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: six rabbits showed slight conjunctival reddening, no chemosis apparent in any treated eyes
Irritant / corrosive response data:
Slight or diffuse conjunctival injection apparent for all six rabbits within an hour of benzyl benzoate instillation. A minimal iridial response was also seen in one treated eye at this assessment. All reactions had resolved within 24 hours of dosing and the eyes were overtly normal for the remainder of the observation period (up to Day 8).
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on only very slight reactions being noted one hour after dosing, all of which had resolved wih in 24 hours, benzyl benzoate was not considered to be irritating to rabbit eyes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Only study available for this endpoint with this substance. Study performed to GLP and to current guidelines

Justification for selection of eye irritation endpoint:
Only study available for this endpoint with this substance. Study performed to GLP and using method similar to current guidelines

Justification for classification or non-classification

The substance benzyl benzoate was found to be non irritant to skin or eye in two in vivo studies using the undiluted substance on rabbit skin or in rabbit eye. This substance is used as read across for the classification of skin and eye irritation of 3-phenyl propyl benzoate (see read across justification document in section 13). Therefore 3 -phenyl propyl benzoate does not require classification for eye or skin irritation under EU Regulation 1272/2008.