1-(2-bromoethoxy)-2-methoxybenzene

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:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according 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)

Test material

Test material information

Constituent 1

Reference substance name:

1-(2-bromoethoxy)-2-methoxybenzene

EC Number:

402-010-4

EC Name:

1-(2-bromoethoxy)-2-methoxybenzene

Cas Number:

4463-59-6

Molecular formula:

C9H11BrO2

IUPAC Name:

1-(2-bromoethoxy)-2-methoxybenzene

Details on test material:

- Name of test material (as cited in study report): Carvedilol 5th intermediate (Bromoethoxy-guaiacol)
- Physical state: reddish brown crystalline powder
- Lot/batch No.: 9803
- Expiration date of the lot/batch: June 2001
- Storage condition of test material: at room temperature

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: TOXI-COOP ZRT. H-1103, Budapest, Cserkesz street 90
- Weight at study initiation: 18.3-21.6 g
- Housing: Type II. Polypropylene/ polycarbonate
- Bedding: Laboratory bedding
- Diet (e.g. ad libitum): ad libitum (Rat/Souris-Elevage E complee diet for rats and mice produced by ssniff Spezialdiaten GmbH )
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 / 12 hours

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

25%, 10%, 5%, 2,5%

No. of animals per dose:

4

Positive control substance(s):

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

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

6.5

Test group / Remarks:

25% in AOO

Results 2

Parameter:

SI

Value:

5.9

Test group / Remarks:

10% in AOO

Results 3

Parameter:

SI

Value:

6.4

Test group / Remarks:

5% in AOO

Results 4

Parameter:

SI

Value:

3

Test group / Remarks:

2.5% in AOO

Cellular proliferation data / Observations:

The maximum dose selection was performed according to the relevant guidelines and based on results of a formulation evaluation and also results of the Dose Range Finding test (DRF). Based on the formulation evaluation the maximum attainable concentration (based on solubility) was 50 % (w/v) in different vehicles recommended by the relevant guidelines (AOO, DMF, DMSO and MEK). As AOO is the most preferred in the LLNA the test item was formulated with this vehicle.
Significant adverse effect (toxicity, indicated by significantly decreased body weight) was observed in the DRF at test concentrations of 50 % (w/v). Based on the results no obvious indication of a similar effect was considered at lower test concentrations. According to this the test item was examined in the main test at 25 %, 10 %, 5 % and 2.5 % (w/v) concentrations as formulations in AOO.
The LLNA was valid and no confounding effects of irritation interfered with the results. The observed effect on the body weights was considered significant only in case of 1 animal (animal no. 159, 10 % decrease) in the 25 % (w/v) dose group. On the other hand the mean body weight did not decrease significantly in this or in the other dose groups and no other symptoms of a systemic effect were observed in any dose group. It is possible that systemic toxicity interfered with the results at 25 % (w/v) concentration but no significant toxicity was considered at the lower test concentrations. The dose-response is considered to be biologically relevant and corresponds to a dose-response observable when interfering effects (systemic or local) occurs at high treatment concentrations. Other mechanisms (such as immunosuppression) may also result in the lack of a significant dose-response correlation although no experimental evidence of presence of these mechanisms can be obtained from the LLNA.
The test item caused significant lymphoproliferation at all test concentrations. The observed stimulation index values were 6.5, 5.9, 6.4 and 3.0 at treatment concentrations of 25 %, 10 %, 5 % and 2.5% (w/v), respectively. Dose-related response was considered but no significant linear correlation was observed.
According to evaluation criteria of the relevant guidelines [1,2], the significantly increased lymphoproliferation (indicated by an SI ≥ 3) at 2.5 % (w/v) concentration and above and the statistically insignificant but biologically relevant dose-related response are considered evidence that Bromethoxy-qvajacol (CVD 21) is a skin sensitizer.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Under the conditions of the present assay, Bromethoxy-qvajacol (CVD 21) tested at concentrations of 25 %, 10 %, 5 % and 2.5 % (w/v) as formulations (apparently solutions) in a suitable vehicle (AOO) was shown to have skin sensitization potential (skin-sensitizer) in the Local Lymph Node Assay.
According to the effective regulations [5,6] concerning to the classification, labelling and packaging of substances and mixtures the following label elements should be used for the test item:
Risk phrase: R43
Hazard class and category: Skin Sens. 1
Hazard statement: H317 “May cause an allergic skin reaction”