Methyl 1,2,3,4-tetrahydro-6-naphthyl ether

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:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (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:

Methyl 1,2,3,4-tetrahydro-6-naphthyl ether

EC Number:

217-049-0

EC Name:

Methyl 1,2,3,4-tetrahydro-6-naphthyl ether

Cas Number:

1730-48-9

Molecular formula:

C11H14O

IUPAC Name:

6-methoxy-1,2,3,4-tetrahydronaphthalene

Test material form:

other: liquid

Details on test material:

Test item: Methoxy-tetraline
CAS number: 1730-48-9
Batch number: S41214K
Physical state: Liquid
Coluor: Brown
Storage: At a temperature of 15 to 30 °C

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Source: TOXI-COOP ZRT.
Hygienic level at arrival: SPF
Hygienic level during the test: Good conventional
Number of animals: 28 animals/main test (4 animals/treatment group)
Sex: Female, nulliparous, non-pregnant
Age of animals: Young adult mice; 10-11 weeks old (at start of the main test)
Body weight range at starting: 18.2-22.4 g
Acclimatization time: 7 days

Housing during acclimatization period: Grouped caging in small groups
Housing during the test: Grouped caging (4 animals/cage)
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 – 70 %

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Remarks:

AOO (acetone:olive oil, 4:1) for positive control groups

Concentration:

The test item was administered at four different concentrations (100; 50; 25; 10 w/v%) according to the results of the dose range finding test.

Details on study design:

Selection of test item concentrations was based on the results of a formulation evaluation and also results of preliminary irritation/toxicity tests to find an appropriate vehicle and the maximum applicable concentration according to the relevant guidelines. Based on the preliminary test results Methoxy-tetraline (CAS No. 1730-48-9) was tested in the LLNA at concentration of 100 % as the undiluted test item and at 50 %, 25 % and 10 % (w/v) concentrations as formulations in Acetone: Olive oil 4:1 (v/v) mixture (AOO). Appropriate positive control (α-Hexylcinnamaldehyde [HCA] in 25 % (w/v) concentration), furthermore two negative control groups dosed with physiological saline (as naive control group), or with the vehicle of the test and positive control groups, respectively, were employed.
The positive control item (25 % (w/v) HCA in AOO) induced the appropriate stimulation over the control, thus confirming the validity of the assay.

Positive control substance(s):

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

Results and discussion

Positive control results:

The positive control group animals were treated with 25 % (w/v) HCA solution (dissolved in AOO) concurrent to the test item groups. No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group.
Significant lymphoproliferative response (SI ≥ 3) was noted for HCA (SI = 15.3). The results of the positive control item demonstrated appropriate performance of the test in accordance with the relevant guidelines and confirmed validity of the assay.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

13.4

Remarks on result:

other: Methoxy-tetraline 100% (undiluted)

Results 2

Parameter:

SI

Value:

3.1

Remarks on result:

other: Methoxy-tetraline 50 % in DMF

Results 3

Parameter:

SI

Value:

2.5

Remarks on result:

other: Methoxy-tetraline  25 % in DMF

Results 4

Parameter:

SI

Value:

1

Remarks on result:

other: Methoxy-tetraline 10 % in DMF

Results 5

Parameter:

EC3

Value:

32

Remarks on result:

other: based on regression curve

Results 6

Parameter:

EC3

Value:

46

Remarks on result:

other: based on dose-response curve

Any other information on results incl. tables

Test Group Name	Measured DPM/group	Group* DPM	DPN (DPM/Node)	Stimulation Index Values
Naive control: physiological saline	2337	2314.0	289.3	1.0
Vehicle control for the positive control: AOO	12954	12931.1	1616.4	1.0
Positive control: 25 % HCA in AOO	197314	197291.0	24661.4	15.3
Methoxy-tetraline 100% (undiluted)	31146	31123.0	3890.4	13.4
Methoxy-tetraline 50 % in DMF	39761	39738.0	4967.3	3.1
Methoxy-tetraline  25 % in DMF	32924	32901.0	4112.6	2.5
Methoxy-tetraline 10 % in DMF	12844	12821.0	1602.6	1.0

*Group DPM = measured DPMgroup- average DPMbackground

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Remarks:

Migrated information

Conclusions:

In conclusion, under the conditions of the present Local Lymph Node Assay, Methoxy-tetraline (CAS No. 1730-48-9) tested at the maximum applicable concentration of 100 % (as the undiluted test item) and at concentrations of 50 %, 25 % and 10 % (w/v) as formulations in an appropriate vehicle (AOO) was shown to have skin sensitization potential. The calculated EC3 values (based on dose-response and regression curve analysis) were 46 % and 32 % (w/v), in this LLNA, respectively. Based on the EC3 values calculated using dose-response and regression curve analysis the test item was considered a weak sensitizer according to the published data.
Using both EC3 values, according to the published data for classification of contact allergens, Methoxy-tetraline (CAS No. 1730-48-9) is ranked among weak sensitizers (10 ≤ EC3 ≤ 100) in this LLNA
According to GHS classification criteria the substance is classified as skin senzitization 1B sub-category.