Bis(2-(2-methoxyethoxy)ethyl) ether

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 Apr - 29 Apr 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The tested substance is strucrally related to the target chemical, exhibiting same chemical fuctional groups. It is assumed that the tested substance and the target substance share the same toxic mode of action.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

13 Apr - 29 Apr 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

The tested substance is structurally related to the target chemical, exhibiting same chemical functional groups. It is assumed that the tested substance and the target substance share the same toxic mode of action.

Reason / purpose for cross-reference:

assessment report

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)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 15 - 25 g
- Housing:single caging
- Diet (e.g. ad libitum): pelleted standard diet (Harlan Laboratories GmbH, 33178 Borchen), ad libidum
- Water (e.g. ad libitum): tap water, (Gemeindewerke, 64380 Rossdorf), ad libitum
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness will be used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): artificial light 6:00 a.m. - 6:00 p.m.

Vehicle:

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

Concentration:

25, 50, and 100%

No. of animals per dose:

4

Details on study design:

In order to study a possible allergenic potential of Diethylenglycol EM, three groups each of four female mice were treated with different concentrations of the test item by topical application at the dorsum of each ear (left and right) on 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 intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed and 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 -scintillation counter.

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated in the body weight tables.

Positive control results:

Experiment performend in November 2009, 5, 10, and 25% alpha-Hexylcinnamaldehyde yielded a S.I. of 1.78, 2.54, and 4.88, respectively. The EC3 value calculated was 12.9%

Parameter:

SI

Value:

0.69

Test group / Remarks:

100%

Parameter:

SI

Value:

1.03

Test group / Remarks:

50%

Parameter:

SI

Value:

0.73

Test group / Remarks:

25%

Test item concentration % (w/v)	Group	Measurement DPM	Calculation			Result
			DPM-BG^a)	number of lymph nodes	DPM per lymph node^b^)	S.I.
---	BG I	16	---	---	---	---
---	BG II	15	---	---	---	---
---	1	4826	4811	8	601.3
25	2	3520	3505	8	438.1	0.73
50	3	4984	4969	8	621.1	1.03
100	4	3345	3330	8	416.2	0.69

BG = Background (1 ml 5% trichloroacetic acid) in duplicate 1 = Control Group 2-4 = Test Group S.I. = Stimulation Index

^a) = The mean value was taken from the figures BG I and BG II ^b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled

The EC3 value could not be calculated, since all S.I.´s are below 3.

Viability / Mortality: No deaths occurred during the study period.

Clinical Signs: No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

Body Weights: The body weight of the animals, recorded prior to the first application and prior to treatment with³HTdR, was within the range commonly recorded for animals of this strain and age.

Analogue Approach Justification (target chemical: tetraglyme; source chamical: EMDE):

EMDE is structurally related to the target chemical, exhibiting same chemical functional groups (ethylene glycol chain, methoxy moiety as well as the structural feature to be metabolized to 2-Methoxyethanol and 2-Methoxyacetic acid). The bioavailability via dermal route as well as metabolic pathways are likely to be comparable.

Interpretation of results:

GHS criteria not met

Conclusions:

No classification is warranted for tetraglyme based on the read-across approach.

Executive summary:

The sensitisation potential of tetraglyme was assessed based on the read-across approach using ethoxy methoxy diethylene glycol (EMDE) as read-across supporting substance. The skin sensitization potential of EMDE was investigated according to OECD 429 and negative result (non-skin sensitizer) was obtained. Likewise, tetraglyme is considered to be a non-skin sensitizer.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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:

1-ethoxy-2-(2-methoxyethoxy)ethane

EC Number:

213-690-5

EC Name:

1-ethoxy-2-(2-methoxyethoxy)ethane

Cas Number:

1002-67-1

Molecular formula:

C7H16O3

IUPAC Name:

1-ethoxy-2-(2-methoxyethoxy)ethane

Constituent 2

Reference substance name:

Diethylene glycol methyl ethyl ether

IUPAC Name:

Diethylene glycol methyl ethyl ether

Constituent 3

Reference substance name:

ethoxymethoxy diethylene glycol

IUPAC Name:

ethoxymethoxy diethylene glycol

Constituent 4

Reference substance name:

EMDE

IUPAC Name:

EMDE

Details on test material:

Purity: 99.8% (m/m)
Stability in solvent: 24 hours in water, propylene glycol, DMSO, DMF, acetone:olive oil (4+1), and methyl ethyl ketone
Storage: At room temperature

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 15 - 25 g
- Housing:single caging
- Diet (e.g. ad libitum): pelleted standard diet (Harlan Laboratories GmbH, 33178 Borchen), ad libidum
- Water (e.g. ad libitum): tap water, (Gemeindewerke, 64380 Rossdorf), ad libitum
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness will be used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 2°C
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): artificial light 6:00 a.m. - 6:00 p.m.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

25, 50, and 100%

No. of animals per dose:

4

Details on study design:

In order to study a possible allergenic potential of Diethylenglycol EM, three groups each of four female mice were treated with different concentrations of the test item by topical application at the dorsum of each ear (left and right) on 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 intravenously injected into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed and 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 -scintillation counter.

Positive control substance(s):

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

Statistics:

The mean values and standard deviations were calculated in the body weight tables.

Results and discussion

Positive control results:

Experiment performend in November 2009, 5, 10, and 25% alpha-Hexylcinnamaldehyde yielded a S.I. of 1.78, 2.54, and 4.88, respectively. The EC3 value calculated was 12.9%

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

0.69

Test group / Remarks:

100%

Results 2

Parameter:

SI

Value:

1.03

Test group / Remarks:

50%

Results 3

Parameter:

SI

Value:

0.73

Test group / Remarks:

25%

Any other information on results incl. tables

Test item concentration % (w/v)	Group	Measurement DPM	Calculation			Result
			DPM-BG^a)	number of lymph nodes	DPM per lymph node^b^)	S.I.
---	BG I	16	---	---	---	---
---	BG II	15	---	---	---	---
---	1	4826	4811	8	601.3
25	2	3520	3505	8	438.1	0.73
50	3	4984	4969	8	621.1	1.03
100	4	3345	3330	8	416.2	0.69

BG = Background (1 ml 5% trichloroacetic acid) in duplicate 1 = Control Group 2-4 = Test Group S.I. = Stimulation Index

^a) = The mean value was taken from the figures BG I and BG II ^b) = Since the lymph nodes of the animals of a dose group were pooled, DPM/node was determined by dividing the measured value by the number of lymph nodes pooled

The EC3 value could not be calculated, since all S.I.´s are below 3.

Viability / Mortality: No deaths occurred during the study period.

Clinical Signs: No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

Body Weights: The body weight of the animals, recorded prior to the first application and prior to treatment with³HTdR, was within the range commonly recorded for animals of this strain and age.

Analogue Approach Justification (target chemical: tetraglyme; source chamical: EMDE):

EMDE is structurally related to the target chemical, exhibiting same chemical functional groups (ethylene glycol chain, methoxy moiety as well as the structural feature to be metabolized to 2-Methoxyethanol and 2-Methoxyacetic acid). The bioavailability via dermal route as well as metabolic pathways are likely to be comparable.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

No classification is warranted for tetraglyme based on the read-across approach.

Executive summary:

The sensitisation potential of tetraglyme was assessed based on the read-across approach using ethoxy methoxy diethylene glycol (EMDE) as read-across supporting substance. The skin sensitization potential of EMDE was investigated according to OECD 429 and negative result (non-skin sensitizer) was obtained. Likewise, tetraglyme is considered to be a non-skin sensitizer.