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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
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 certificate of compliance from UK GLP Monitoring Authority included in report
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Propane-1,2-diyl dibenzoate
EC Number:
242-894-7
EC Name:
Propane-1,2-diyl dibenzoate
Cas Number:
19224-26-1
Molecular formula:
C17H16O4
IUPAC Name:
2-(benzoyloxy)propyl benzoate
Constituent 2
Reference substance name:
1,2-propan-diyl-dibenzoate
IUPAC Name:
1,2-propan-diyl-dibenzoate
Constituent 3
Reference substance name:
K-FLEX* PG
IUPAC Name:
K-FLEX* PG
Test material form:
other: clear light yellow liquid
Details on test material:
- Name of test material (as cited in study report): Kalama® K-FLEX® PG
- Substance type: Plasticizer
- Physical state: Colourless to pale yellow liquid
- Analytical purity: 97.1% propylene glycol esters
- Lot/batch No.: KAKPG43301
- Expiration date of the lot/batch: 05 March 2016
- Storage condition of test material: Ambient temperature

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: 8-12 weeks
- Weight at study initiation: 17.2 to 21.5 g
- Housing: 2 per cage
- Diet: 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): not reported
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

IN-LIFE DATES: From: 24 April 2014 To: 2 June 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:
2 - preliminary study
4 - main study
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 µL 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 was treated by the tip of an empty pipette being passed over the surface of the ear.

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 µL of phosphate buffered saline containing 3H-methyl Thymidine (3HTdR: 80 µCi/mL) giving a nominal 20 µCi 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)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
0.9
Test group / Remarks:
5% v/v PDGB
Key result
Parameter:
SI
Value:
1.6
Test group / Remarks:
50% v/v PGDB
Key result
Parameter:
SI
Value:
6.3
Test group / Remarks:
as supplied’ PGDB
Key result
Parameter:
SI
Value:
10.6
Test group / Remarks:
Positive Control - hexyl cinnamic aldehyde (HCA)
Key result
Parameter:
EC3
Value:
52.2
Test group / Remarks:
PGDB
Key result
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
The SI (test/control ratios) obtained for 25, 50% v/v and ‘as supplied’ PGDB 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), PGDB was considered to have the potential to cause skin sensitization. Based on the results of this study the EC3 value is calculated to be 52.2% v/v. The SI for the positive control substance hexyl cinnamic aldehyde (HCA) was 10.6 which demonstrates the validity of this study.
Key result
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
Group 3 sham control: 6808.35 dpm and 851.04 dpm/node Group 4 vehicle: 5119-65 dpm and 639.96 dpm/node Group 5 25% v/v: 9756.55 dpm and 1219.57 dpm/node Group 6 50% v/v: 19744.35 dpm and 2468.04 dpm/node Group 7 as supplied 26483.75 dpm and 3310.47 dpm/node Group 8 HCA 25% v/v 71843.55 dpm and 8980.44 dpm/node

Applicant's summary and conclusion

Interpretation of results:
other: Sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on an LLNA study, PGDB is regarded as a potential skin sensitizer. The EC3 value was calculated to be 52.2% v/v.
Executive summary:

The SI (test/control ratios) obtained for 25, 50% v/v and ‘as supplied’ PGDB were 1.4, 2.9 and 5.2 respectively. As a SI of 3 or more was recorded for the highest concentration tested (as supplied), PGDB was considered to have the potential to cause skin sensitization. Based on the results of this study the EC3 value is calculated to be 52.2% v/v. The SI for the positive control substance hexyl cinnamic aldehyde (HCA) was 10.6 which demonstrates the validity of this study.

PGDB is regarded as a potential skin sensitizer.