2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-04-27 to 2005-05-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

1) Insufficient information on the test substance, test animals and methodological details presented

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test method 595.12

Deviations:

not specified

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but no formal claim of GLP compliance is made for the study.

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol

EC Number:

283-585-7

EC Name:

2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol

Cas Number:

84682-23-5

Molecular formula:

C14H14Cl2N2O3

IUPAC Name:

[2-(2,4-dichlorophenyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolan-4-yl]methanol

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): JNJ-16479489-AAA (T001159)
- Physical state: solid
- Appearance: off-white powder

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

5, 10 and 25% (w/w) in dimethylformamide
A further group of four animals was treated with dimethyl formamide alone.

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS: no signs of systemic toxicity at a concentration of 25% w/w in a preliminary sighting test

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: A stimulation index of 3.0 or greater indicates a positive result.

TREATMENT PREPARATION AND ADMINISTRATION:
- These groups were treated with 50 µL (25 µL per ear) of the test substance as a solution in dimethylformamide.

Positive control substance(s):

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

other: 2,4 Dinitrobenzene sulphonic acid, sodium salt (DNBS), at 1%, 10%, 20% v/v in 1% pluronic L92 in distilled water.

Statistics:

no data

Results and discussion

Positive control results:

see: any other information on results (here below)

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.86

Test group / Remarks:

5% w/w in dimethyl formamide

Results 2

Parameter:

SI

Value:

1.65

Test group / Remarks:

10% w/w in dimethyl formamide

Results 3

Parameter:

SI

Value:

1.86

Test group / Remarks:

25% w/w in dimethyl formamide

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA
Dpm/node obtained by dividing the Dpm valule by 8 (total number of lymph nodes)
vehicle control group, Dpm/node: 565.23
5% w/w group: Dpm/node: 1053.65
10% w/w group: Dpm/node: 933.70
25% w/w group: Dpm/node: 1049.38

DETAILS ON STIMULATION INDEX CALCULATION
The Stimulation Index (SI) was expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group

EC3 CALCULATION
no data

CLINICAL OBSERVATIONS:
No signs of systemic toxicity have been observed, no mortality observed
White residual test material on the ears observed in 10 and 25 %w/w groups 1 hour post dose on day 1 (only 25% w/w group) and days 2 and 3

BODY WEIGHTS
The mean body weight gain shown by the animals over the study period was considered to be normal.

Any other information on results incl. tables

Positive Control Local Lymph Node Assay in the Mouse (2005)

Start Date	Finish Date	Test Material	Concentration	Vehicle	Stimulation Index^a	Classification^b
04/03/2005	10/03/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	acetone/olive oil 4:1	2.76, 3.34, 8.91	Positive
20/04/2005	26/04/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	ethanol/distilled water 7:3	2.64, 8.36, 12.94	Positive
14/07/2005	20/07/2005	α‑Hexylcinnamaldehyde, tech., 85%	5%, 10%, 25% v/v	1% pluronic L92 in distilled water	0.86, 1.50, 6.17	Positive
14/07/2005	20/07/2005	2,4 Dinitrobenzene sulphonic acid, sodium salt (DNBS)	1%, 10%, 20% v/v	1% pluronic L92 in distilled water	1.16, 9.59, 20.71	Positive

a=        Ratio of test to control lymphocyte proliferation

b=        Stimulation index greater than 3.0 indicates a positive result

* =        Standard Test Method 595 (Pooled nodes)

·=        Standard Test Method 599 (Individual nodes)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was not considered a sensitiser under the conditions of the test as no SI value >= 3 has been observed when tested up to a concentration of 25% w/w.