3-phenylpropyl benzoate

Endpoint summary

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

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.