1,2-bis(2-methoxyethoxy)ethane

Endpoint summary

Description of key information

The skin sensitization potential of Triethylene glycol dimethyl ether is assessed based on the read-across to Diethylene glycol ethyl methyl ether und 2-Methoxy ethanol. Both read-across surrogates are non skin sensitizer. Likewise, Triethylene glycol dimethyl ether is expected to be a non skin sensitizer. 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Triethylene glycol dimethyl ether and Diethylene glycol methyl ethyl ether belong to the glycol ether family. Due to the fact that Triethylene glycol dimethyl ether and Diethylene glycol methyl ethyl ether have nearly the same chemical structure (especialy with reference to the functional groups):

1. Triethylene glycol dimethyl ether:H3C-O-CH2-CH2-O-CH2 -CH2 -O-CH2 -CH2 -O-CH3

2. Diethylene glycol methyl ethyl ether:H3C-O-CH2-CH2-O-CH2-CH2-O-CH2-CH3

the same mode of interaction with living cells and tissue is expected. Therefore, a read-across from Triethylene glycol dimethyl ether to data obtained with Diethylene glycol methyl ethyl ether is scientifically justified.

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:

0.73

Test group / Remarks:

25%

Remarks on result:

other:

Parameter:

SI

Value:

1.03

Test group / Remarks:

50%

Remarks on result:

other:

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.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item Diethylenglycol EM was not a skin sensitiser under the described conditions.

Executive summary:

Triethylene glycol dimethyl ether and Diethylene glycol methyl ethyl ether, which is tested for its sensitising potential, belong to the glycol ether family. These substances have been demonstrated to be very similar in structure, physical/chemical properties and the toxicological profile. Due to the fact that Triethylene glycol dimethyl ether and Diethylene glycol methyl ethyl ether have nearly the same chemical structure (especialy with reference to the functional groups):

1. Triethylene glycol dimethyl ether:H₃C-O-CH₂-CH₂-O-CH₂ -CH₂ -O-CH₂ -CH₂ -O-CH₃

2. Diethylene glycol methyl ethyl ether:H₃C-O-CH₂-CH₂-O-CH₂-CH₂-O-CH₂-CH₃

the same mode of interaction with living cells and tissue is expected. Therefore, a read-across from Triethylene glycol dimethyl ether to data obtained with Diethylene glycol methyl ethyl ether is scientifically justified.

 

The present study (Vogel 2010) analyses the sensitising potential of Diethylenglycol EM

Three groups each of four female mice were treated daily with the test item at concentrations of 25, 50, and 100% (w/v) in acetone:olive oil (4+1) by topical application to the dorsum of each ear (left and right) for three consecutive days. A control group of four mice was treated with the vehicle (acetone:olive oil (4+1)) only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (³H-methyl thymidine). Approximately five hours after intravenous injection, the mice were sacrificed, 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 of³H-methyl thymidine measured in ab-scintillation counter.

All treated animals survived the scheduled study period and no signs of toxicity were observed.

In this study Stimulation Indices of 0.73, 1.03, and 0.69 were determined with the test item at concentrations of 25, 50, and 100% in acetone:olive oil (4+1). The EC3 value could not be calculated, since none of the tested concentrations induced an S.I. greater than 3.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

The skin sensitization property of triethylene glycol dimethyl ether is derived based on read-across to Diethylene glycol ethyl methyl ether and 2-Methoxyethanol. Both read-across surrogates are non-skin skin sensitizer. Likewise triethylene glcol dimethyl ether is expected to be a non-skin sensitizer. No classification is warranted.