3-phenylpropyl benzoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

05 December 2013 to21 January 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to approved guidelines and in compliance with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Copy of scertificate of compliance form UK GLP Monitoring Authority included in report

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

3-phenylpropyl benzoate

EC Number:

611-930-7

Cas Number:

60045-26-3

Molecular formula:

C16H16O2

IUPAC Name:

3-phenylpropyl benzoate

Test material form:

other: clear liquid

Details on test material:

- Name of test material (as cited in study report): 3-PPB

- Substance type: organic
- Physical state: clear, colourless liquid
- Analytical purity:99.1%

- Purity test date:
- Lot/batch No.: EH101912A
- Expiration date of the lot/batch: 19 October 2104

- Storage condition of test material: Room temperature under nitrogen
- Other:

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: UK
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 18-20.3 g
- Housing:2 per cage
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 deg C
- Humidity (%): 40-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):12 h dark/12 h light

IN-LIFE DATES: From: 11 December 21013 To:20 January 2014

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

as supplied and then 50% and 25% of "as supplied" solution

No. of animals per dose:

4

Details on study design:

The results of the preliminary investigations indicated that ‘as supplied’ was a suitable high
concentration for administration in the main phase of the study. The low and intermediate
concentrations were selected from the concentration series given in regulatory guidelines and
the concentrations administered on the main study were:
25, 50% v/v in AOO and ‘as supplied’
The positive control group received 25% v/v hexylcinnamic aldehyde in AOO based on
previous experience at this laboratory.

Main phase
Groups of four mice were treated at one of three concentrations of the test substance. The
mice were treated by daily application of 25 L of the appropriate concentration of the test
substance to the dorsal surface of each ear for three consecutive days (Days 1-3). The test
substance was applied to the dorsal surface of each ear using an automatic micropipette and
was spread over the entire dorsal surface of the ear using the tip of the pipette. Further
groups of four mice received the vehicle alone or the positive control substance in the same
manner and a sham control group

Administration of 3H-methyl Thymidine
In the main phase of the study, five days following the first topical application of test
substance (Day 6) all mice were injected via the tail vein with 250 L of phosphate buffered
saline containing 3H-methyl Thymidinea (3HTdR: 80 Ci/mL) giving a nominal 20 Ci to
each mouse. The injection into the tail vein was carried out using a plastic syringe and needle
after the mouse had been heated in a warming chamber

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

None stated

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

The SI (test/control ratios) obtained for 25, 50% v/v and ‘as supplied’ 3-Phenylpropyl benzoate were 0.9, 1.6 and 6.3 respectively. As a SI of 3 or more was recorded for the highest concentration tested (as supplied), 3-Phenylpropyl benzoate was considered to have the potential to cause skin sensitization. Based on the results of this study the EC3 value is calculated to be 64.9% v/v. The SI for the positive control substance hexyl cinnamic aldehyde (HCA) was 6.5 which demonstrates the validity of this study.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Group 2 Sham control: 1593.70 dpm and 199.21 dpm/node Group 3 vehicle: 1870.80 dpm and 233.85 dpm/node Group 4 25% v/v: 1698.00 dpm and 212.25 dpm/node Group 5 50% v/v: 3046.50 dpm and 380.81 dpm/node Group 6 "as supplied" 10060.30 dpm and 1257.54 dpm/node Group 7 HCA 25% v/v 12252.40 dpm and 1531.55 dpm/node

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

3-Phenylpropyl benzoate is regarded as a weak skin sensitizer. The EC3 value was calculated to be 64.9% v/v.

Executive summary:

The SI (test/control ratios) obtained for 25, 50% v/v and ‘as supplied’ 3-Phenylpropyl benzoate were 0.9, 1.6 and 6.3 respectively. As a SI of 3 or more was recorded for the highest concentration tested (as supplied), 3-Phenylpropyl benzoate was considered to have the potential to cause skin sensitization. Based on the results of this study the EC3 value is calculated to be 64.9% v/v. The SI for the positive control substance hexyl cinnamic aldehyde (HCA) was 6.5 which demonstrates the validity of this study.

3-Phenylpropyl benzoate is regarded as a potential skin sensitizer