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

Endpoint summary

Description of key information

Skin sensitization

In a Local Lymph Node Assay (LLNA) in mice (CBA/Ca strain), according to OECD Guideline 429 and SPL Standard Test method 595.12, T001159 did not elicit a SI>= 3 when tested up to 25% (Sanders, 2005). Therefore, the test item does not have to be classified as a skin sensitizer and has no obligatory labelling requirement for sensitization by skin contact according to the CLP Regulation (EC) No. 1272/2008.

Respiratory sensitization

No reliable respiratory sensitization study was available

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

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

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)

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

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

Positive control results:

see: any other information on results (here below)

Parameter:

SI

Value:

1.86

Test group / Remarks:

5% w/w in dimethyl formamide

Parameter:

SI

Value:

1.65

Test group / Remarks:

10% w/w in dimethyl formamide

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.

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)

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a Local Lymph Node Assay (LLNA) in mice (CBA/Ca strain), the skin sensitization potential of T001159 was investigated following topical application to the dorsal surface of the ear of mice (Sanders, 2005). Test item concentrations selected for the main study were based on the results of a preliminary sighting test. Three groups, each of four animals, were treated with 50 µL of the test material (25 µL per ear) as a solution in dimethyl formamide at concentrations of 5%, 10% and 25% w/w. A further group of four animals was treated with dimethyl formamide alone. Clinical observations and checks for mortality were recorded pre- and 1-hour post-dose on Days 1, 2, and 3 and on Days 4, 5, and 6. Body weights were recorded on Day 1 and 6. The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).

Positive control tests using hexyl cinnamic aldehyde (CAS 101-86-0) at 5, 10 and 25% v/v in acetone/olive oil 4:1 and 2,4 Dinitrobenzene sulphonic acid, sodium salt (DNBS), at 1, 10, and 20% v/v in 1% pluronic L92 in distilled water elicited a positive classification.

No mortality or signs of systemic toxicity were 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. The mean body weight gain shown by the animals over the study period was considered to be normal. Mean DPM/node (DPM value/8 total lymph nodes) for the experimental groups treated with test item concentrations 5, 10 and 25% were 1053.65, 933.70 and 1049.38, respectively. The mean DPM/node value for the vehicle control group was 565.23. The SI values calculated for the substance concentrations 5, 10 and 25% were 1.86, 1.65 and 1.86, respectively. As T001159 did not elicit a stimulation index (SI) greater than or equal to 3 when tested up to 25%, it was considered to be a non-sensitiser under the conditions of the test.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitisation:

As T001159 did not elicit a stimulation index (SI) greater than or equal to 3 when tested up to 25%, it is not considered to be a skin sensitizer under the conditions of the test.

Respiratory sensitisation:

No data were available to decide on the classification for respiratory sensitisation.