α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study according to internationally accepted guidelines and CLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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:

α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol

EC Number:

246-042-5

EC Name:

α-(2,4-dichlorophenyl)-1H-imidazole-1-ethanol

Cas Number:

24155-42-8

Molecular formula:

C11H10Cl2N2O

IUPAC Name:

1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-ol

Test material form:

solid: crystalline

Details on test material:

Test item: IMIDAZOLE ETHANOL (CAS No. 24155-42-8)
Batch No.: L36066N
Physical state: Light-yellow powder
Active ingredient content (titrimetry): 92.1%
Impurities (HPLC): 9.18%
Storage: 15-30°C

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Species and strain: CBA/Ca mice
Source: TOXI-COOP ZRT.
Hygienic level at arrival: SPF
Hygienic level during the test: Good conventional
Number of animals: 4 animals/preliminary test (2 animals/treatment group)
Sex: Female, nulliparous, non pregnant
Age of animals: Young adult mice; 11-12 weeks old (at start of the preliminary test)
Body weight range at starting: 17.0-22.3 g
Acclimatization time: 7 days
Animal health: Only healthy animals were used

Housing during acclimatization period: Grouped caging in small groups
Housing during the test: Grouped caging (4 animals/cage)
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 – 70 %

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Remarks:

AOO (acetone:olive oil, 4:1) for positive control groups

Concentration:

The test item was administered at four different concentrations (25; 10; 5; 2.5 w/v%) according to the results of the dose range finding test.

No. of animals per dose:

4 animal/dose

Details on study design:

Selection of test item concentrations was based on the results of a formulation evaluation and also results of preliminary irritation/toxicity test to find the best solvent and the maximum applicable concentration according to the relevant guidelines. The test item was tested at the solubility limit of 25 % and at three lower concentrations (10 %, 5 % and 2.5 %) in N,N-Dimethylformamide (DMF). Appropriate positive control (α-Hexylcinnamaldehyde [HCA] in 25 % concentration), furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed.
The positive control item (25 % HCA in Acetone: Olive oil 4:1 mixture, AOO) induced the appropriate stimulation over the control, thus confirming the validity of the assay.

Positive control substance(s):

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

Results and discussion

Positive control results:

The positive control group animals were treated with 25 % (w/v) HCA solution (dissolved in AOO) concurrent to the test item groups. No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group.
Significant lymphoproliferative response (SI ≥ 3) was noted for HCA (SI = 8.1). The results of the positive control item demonstrated appropriate performance of the test in accordance with the relevant guidelines and confirmed validity of the assay.

In vivo (LLNA)

Results

Parameter:

SI

Value:

2.3

Remarks on result:

other: see Remark

Remarks:

The stimulation index (SI = the DPN of a treated (positive control or test item) group divided by the DPN of the respective negative control group) for each treatment group was also calculated. A stimulation index of 3 or greater is an indication of a positive result. Based on the results EC3 value (dose calculated to induce a stimulation index of 3) of the test item was not calculated.Dose-response relationship was evaluated by linear regression. All calculations were made by Microsoft Excel Software. (See Table1 for the values.)

Any other information on results incl. tables

Test Group Name	Measured DPM/group	Group * DPM	DPN (DPM/Node)	Stimulation Index Values
Vehicle control for the positive control: AOO	17750	17710.5	2213.8	1.0
Positive control: 25% HCA in AOO	144132	144092.5	18011.6	8.1
IMIDAZOLE ETHANOL 25% in DMF	16576	16536.5	2067.1	2.3
IMIDAZOLE ETHANOL 10% in DMF	11831	11791.5	1473.9	1.6
IMIDAZOLE ETHANOL 5% in DMF	14333	14293.5	1786.7	2.0
IMIDAZOLE ETHANOL 2.5% in DMF	8751	8711.5	1088.9	1.2
Vehicle control for the test item: DMF	7226	7186.5	898.3	1.0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Under the conditions of the present Local Lymph Node Assay, “IMIDAZOLE ETHANOL” (CAS No. 24155-42-8) tested at the maximum attainable concentration of 25 % (w/v, based on solubility) and at concentrations of 10 %, 5 % and 2.5 % as formulations in an appropriate vehicle (DMF) was shown to have no sensitization potential.