2-methoxy-4-(methoxymethyl)phenol

Endpoint summary

Description of key information

Skin sensitization: similar to OECD TG 429: sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 17 and 20 January 2006.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Some deviations from the

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: Crl:NMRI, albino

Sex:

female

Details on test animals and environmental conditions:

Dissiminated (delete when editing)
Adapt information
Female Crl:NMRI strain mice were supplied by Charles River Deutschland GmbH, D-97633 Sulzfeld. An acclimatisation period of at least five days was allowed. At the start of the study the animals were in the weight range of 30-36 g, and were nine to ten weeks old.

The animals were housed in groups in transparent macrolone cages (type 150, floor area 810 cm2) with six animals in each cage. The cages were cleaned and bedding changed at least twice a week. Free access to tap water and food (Altromin 1314 pelleted complete rodent diet supplied by Altromin GmbH, Lage, Lippe) was allowed throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 21°C ± 3°C and 30-70%, respectively. The rate of air exchange was 10 changes per hour and the lighting was twelve hours continuous light (06.00 to 18.00) and twelve hours darkness.

Details on study design:

deviations

Vehicle:

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

Remarks:

according to CLP and its updates (EU 1272/2008)

Concentration:

Test item was tested at concentrations of 10, 25 and 50 %.

No. of animals per dose:

Groups of six mice were treated

Details on study design:

Mice were treated by daily application of 25 µl of the chosen concentrations of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). A further group of six mice received the vehicle alone in the same manner.
The bodyweight was recorded on Day 1 (prior to dosing) and on Day 4.
The thickness of each ear was measured using an Oditest micrometer, pre dose on Day 1 and post dose on Day 4. Any changes in the ear thickness were noted.
Control tests with positive reference substances were performed in order to verify the experimental technique. The last such experiment prior to the current study was performed in September 2003.

Bodyweights: The bodyweight of each mouse was recorded on Day 1 (prior to dosing) and Day 4 (prior to termination).

Terminal Procedures
On day 4, after weighing and ear thickness measurement, all mice were killed by inhalation of carbon dioxide and a dissection with removal of the auricular lymph nodes was carried out.

After killing the animals, the lymph node pairs were weighed and lymph node cell suspensions were prepared by mechanical tissue disruption. The cell counts per millilitre of these suspensions were determined manually by Trypan blue exclusion using a Neubauer-chamber.

A difference between this study and the typical LLNA studies is that in this study the lymph node cells were counted without radiolabel.

Positive control substance(s):

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

Positive control results:

The positive control item, undiluted α-Hexylcinnamaldehyde, gave a Differentiation Index of 2.28 and sensitizing potential.

Key result

Parameter:

other: NOAEL

Value:

25

Parameter:

other: Differentiation index

Remarks:

at 50% test item concentration

Value:

3.75

The treatment with the 50% test item caused a reaching of the positive threshold value concerning the lymph node cell count index. But a positive ear swelling was not recorded. For the 50% concentration of the test item a differentiation index of 3.75 was determined. This provides the evidence for the sensitisation potential of the test item.

Interpretation of results:

other: Skin sensitising (category 1B)

Remarks:

in accordance with EU CLP 1272/2008 and its amendments

Conclusions:

The test item was considered to be a skin sensitiser under the conditions of the test and resulted in a NOEC of 25%.

Executive summary:

The skin sensitisation potential of the test substance has been tested similar to OECD TG 429: Local Lymph Node Assay" method. The substance was tested at 10, 25 and 50%.

The treatment with the 50% test item caused a reaching of the positive threshold value concerning the lymph node cell count index. But a positive ear swelling was not recorded. For the 50% concentration of the test item a differentiation index of 3.75 was determined. The NOEC was 25%. Overall, the test item was considered skin sensitizer in this study.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The skin sensitisation potential of the test substance has been tested similar to OECD TG 429: Local Lymph Node Assay" method. The substance was tested at 10, 25 and 50%.

The treatment with the 50% test item caused a reaching of the positive threshold value concerning the lymph node cell count index. But a positive ear swelling was not recorded. For the 50% concentration of the test item a differentiation index of 3.75 was determined. The NOEC was 25%. Overall, the test item was considered skin sensitizer in this study.

Justification for classification or non-classification

Based on the results in the skin sensitization test (sensitizing), the substance needs to be classified as a skin sensitizer 1B according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and its updates.