Diallyl isophthalate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

17 December 2002 to 06 January 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

ANALOGUE APPROACH JUSTIFICATION
Please refer to attached document.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Diallyl phthalate

EC Number:

205-016-3

EC Name:

Diallyl phthalate

Cas Number:

131-17-9

Molecular formula:

C14H14O4

IUPAC Name:

1,2-Benzenedicarboxylic acid, di-2-propenyl ester

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Diallyl phthalate
- Molecular formula (if other than submission substance): C14 H14 O4
- Molecular weight (if other than submission substance): 246.26
- Smiles notation (if other than submission substance): C=CCOC(=O)c1ccccc1C(=O)OCC=C
- InChl (if other than submission substance): InChI=1/C14H14O4/c1-3-9-17-13(15)11-7-5-6-8-12(11)14(16)18-10-4-2/h3-8H,1-2,9-10H2
- Structural formula attached as image file (if other than submission substance): see figure below
- Substance type: organic
- Physical state: liquid
- Analytical purity:
- Impurities (identity and concentrations):
- Purity test date:no data
- Lot/batch No.: 12092
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: Approx 4°C, in the dark, under nitrogen
- Other: Date received 02 October 2002

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Commercial laboratory animal supplier
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 15 to 23g
- Housing: individually housed in suspended solid-floor polypropylene cages furnished with softwood flakes.
- Diet: Free access to Certified Rat and Mouse Diet supplied by International Product Supplies Ltd., Wellingborough, UK.
- Water: tap water ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Humidity: 30 to 70%
- Air changes (per hr): 15
- Photoperiod: 12 hr light and 12 hours dark

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

0.5, 5,and 50 %w/v

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: none
- Lymph node proliferation response: none

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response: radioactive disintergrations per minute per lymph node as a ratio of the 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

TREATMENT PREPARATION AND ADMINISTRATION:
Groups of four mice were treated with the test material at concentrations of 0.5%, 5% or 50% w/v in acetone/olive oil 4:1. The mice were treated by daily application of 25µl of the appropriate concentration of the test material to the dosrsal surface of each ear for three consecutive days Days 0, 1, and 2). The test material formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette. A further group of four mice received the vehicle alone in the same manner.

Five days following the first topical application of the test material (day 5) all mice were injected via the tail vein with 250 µl of phophate buffered saline containing 3H-methyl thymidine (3HTdR: 80 µCi/ml, specific activity 2.0 Ci/mmol) giving a total of 20 µCi to each mouse.

Positive control substance(s):

other: none

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

0.98

Test group / Remarks:

0.5%

Results 2

Key result

Parameter:

SI

Value:

3.23

Test group / Remarks:

5%

Results 3

Key result

Parameter:

SI

Value:

10.74

Test group / Remarks:

50%

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was classified as a sensitiser.