1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-diol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-09-13 to 2011-10-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 22 July 2010

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (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:

R,R-1-(4-tert-butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Molecular formula:

C20H26O3

IUPAC Name:

R,R-1-(4-tert-butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Constituent 2

Reference substance name:

R,S-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Molecular formula:

C20H26O3

IUPAC Name:

R,S-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Constituent 3

Reference substance name:

S,S-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Molecular formula:

C20H26O3

IUPAC Name:

S,S-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Constituent 4

Reference substance name:

S,R-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Molecular formula:

C20H26O3

IUPAC Name:

S,R-1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol

Test material form:

solid

Details on test material:

Minimum purity 95% w/w

Specific details on test material used for the study:

Designation: Art. 132720
Synonym: Avodiol
CAS-No.: 955359-35-0
Batch: 11/LE/016K1
Purity: 95.1% (w/w)
Appearance: white solid
Released until: 2012-05-18

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Manston Road, Margate, Kent, CT9 4LT, United Kingdom
- Age at beginning of treatment: 8- 10 weeks
- Body weight at beginning of treatment: 16.6 - 21.1 g
- Housing: group
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:6 days prior start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

5%
10%
25%

No. of animals per dose:

Control group: 4/group
test item groups: 4/group

Details on study design:

The study was performed according to OECD TG 429 (radioactive method).
The test item concentrations for the main study were established based on the results of a pre-test including ear thickness measurement using 2 mice. The radioactivity of the pooled lymph nodes were analyzed to investigate the skin sensitising potential of the test item.

Positive control substance(s):

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

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1.1

Test group / Remarks:

5%

Results 2

Parameter:

SI

Value:

1.4

Test group / Remarks:

10%

Results 3

Parameter:

SI

Value:

2.4

Test group / Remarks:

25%

Any other information on results incl. tables

Study Design

In order to study a possible skin sensitising potential of the test item, three groups each of four female mice were treated once daily with the test item at concentrations of 5, 10, and 25% (w/v) in acetone:olive oil (4:1, v/v) by topical application to the dorsum of each ear for three consecutive days. A control group of four mice was treated with the vehicle only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, the draining auricular lymph nodes excised and pooled per group. Single cell suspensions of lymph node cells were prepared from pooled lymph nodes, which were subsequently washed and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of 3H-methyl thymidine measured in a beta-scintillation counter.

Results

All treated animals survived the scheduled study period. Neither clinical signs on the ears of the animals nor systemic findings were observed during the study period. The results obtained (Stimulation Index, SI) are reported in the following table.

	Test item conc [%]	S.I.
Group 2	5	1.1
Group 3	10	1.4
Group 3	25	2.4

A calculation of the EC3 value was not performed as no test item concentration produced a S.I. of 3 or higher.

Conclusion

The test item is not a skin sensitiser under the conditions of this study.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not a skin sensitiser under the test conditions of this study and thus no classification for skin sensitisation is needed according to CLP-Regulation (EC) No 1272/2008.

Executive summary:

see above