Reaction mass of 2-[[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]methyl]oxirane and 1,3-bis[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]propan-2-ol and 1-[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]-3-[4-[[4-[3-[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]-2-hydroxy-propoxy]-3,5-dimethyl-phenyl]methyl]-2,6-dimethyl-phenoxy]propan-2-ol

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

1,3-bis[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]propan-2-ol; 1-[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]-3-{4-[(4-{3-[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]-2-hydroxypropoxy}-3,5-dimethylphenyl)methyl]-2,6-dimethylphenoxy}propan-2-ol; 2-{[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]methyl}oxirane

EC Number:

941-357-0

Molecular formula:

Not applicable for multi-constituent substances

IUPAC Name:

1,3-bis[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]propan-2-ol; 1-[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]-3-{4-[(4-{3-[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]-2-hydroxypropoxy}-3,5-dimethylphenyl)methyl]-2,6-dimethylphenoxy}propan-2-ol; 2-{[4-({3,5-dimethyl-4-[(oxiran-2-yl)methoxy]phenyl}methyl)-2,6-dimethylphenoxy]methyl}oxirane

Test material form:

other: Liquid

Details on test material:

Batch: DG4K30997A
Test substance storage: At room temperature protected from light
Stable under storage conditions until 25 October 2015 (expiry date)

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: variation was within ± 20% of the sex mean.
- Housing: Group housed
- Diet (e.g. ad libitum): ad libitum to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 24°C
- Humidity (%):40 to 70%
- Air changes (per hr):approximately 10 room air changes/hour
- Photoperiod (hrs dark / hrs light):12-hour light/12-hour dark cycle.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

0, 10, 25 and 50 % (test substance w/w)

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Two test substance concentrations were tested; a 25% and 50% concentration. The highest concentration was the maximum concentration as
required in the test guidelines (50% for solids).
- Irritation: No irritation and no signs of systemic toxicity were observed in any of the animals examined.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (1 per day)
- Exposure period: Days 1-3
- Test groups: 2,3,4
- Control group: 1
- Site: Dorsal surface of both ears (25 uL/ear)
- Frequency of applications: Once per day (Each ear) at approximately the same time each day
- Concentrations: 0, 10, 25 or 50% (test substance w/w)
- Exision of the nodes was undertaken on Day 6.
Each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) (Merck, Darmstadt, Germany) containing 20 μCi of
3H-methyl thymidine (PerkinElmer Life and Analytical Sciences, Boston, MA, US). After approximately 5 hours animals were killed and the nodes
excised.

Positive control substance(s):

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

Statistics:

Statistical analysis not conducted, as not a requiement of the guideline.

Results and discussion

Positive control results:

The SI values calculated for the substance concentrations 5, 10 and 25% were 1.2, 1.4 and 4.7 respectively. An EC3 value of 9.8% was calculated
using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. .
Based on the results, it was concluded that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing
for contact hypersensitivity.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

3.8

Test group / Remarks:

10%

Results 2

Parameter:

SI

Value:

10.4

Test group / Remarks:

25%

Results 3

Parameter:

SI

Value:

18.8

Test group / Remarks:

50%

Results 4

Parameter:

other: disintegrations per minute (DPM)

Value:

>= 793 - <= 14 941

Test group / Remarks:

0%: 793 ± 77 10%: 3004 ± 353 25%: 8266 ± 1725 50%: 14941 ± 3700

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results indicate that the test substance could elicit an SI >/= 3. The data showed a dose response and the EC3 value was established to be between 0 and 10%. The test substance is a contact skin sensitiser

Based on the results, the test substance would be classified as a skin irritant category 1 according to the CLP regulation (EC) No 1272/2008, as amended.