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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source and target substances or their components are from the same homologous series and contain identical structural groups. All of the groups in the target substances are seen in the source substance. Physicochemical properties are very similar. The source substances are mixtures where one of the main components is the target substance (35-40%).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target: Multiconstituent substance of Tetraethylene glycol methyl ether (TetraEGME) and pentaethylene glycol methyl ether (PentaEGME).
Source: Formulated brake fluids. These are primarily mixtures of triethylene glycol methyl ether (TEGME) TetraEGME and pentaEGME that is partially borated. The borate ester hydrolyses rapidly in the presence of water so the test substance for this end point can be considered a mixture of the parent glycol ether and boric acid (4.5%).

3. ANALOGUE APPROACH JUSTIFICATION
See hypothesis above. If the substance had any potential for skin sensitisation, since there is sufficient of the target substance in the source substance (and arguably a very substantial proportion) it would be evident from the testing of brake fluid formulations containing the substance if the substance itself had any sensitising potential.

4. DATA MATRIX
Multiple studies indicate no skin sensitisation potential.
Supporting information is given from a published QSAR that indicates no alerts for skin sensitisation and from other published data that indicate that the E series glycol ethers as a whole do not show any evidence of skin sensitisation potential (ECETOC 2005. The toxicology of glycol ethers and its relevance to man, Technical Report 95, ECETOC, Brussels, 2005). The available information is sufficient to determine the classification requirements for this end point.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
March 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study is similar to OECD guideline regulatory studies, methods are well reported, but study is not GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study does not need to be conducted because adequate reliable data is available from this alternative existing study providing data on the potential for skin sensitisation
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Animals, after acclimatisatino period, were housed 2-3/cage and provided food and water ad libitum. Room was maintained at 19-23C, with 30-70% relative humidity. Light was maintained on a 12-hour cycle.
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
0.6% in FCA (induction)
100% epicutaneous induction phase
60% in challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.6% in FCA (induction)
100% epicutaneous induction phase
60% in challenge
No. of animals per dose:
10/sex for treated animals, 5/sex for the negative control
Details on study design:
Range finding test on 2 animals/sex was carried out to determine the maximum concentration for the intradermal induction. Animals were closely shorn in the shoulder region, and two rows of intradermal injections were made on either side of the midline. 0.1 mL of Freund's Complete Adjuvant, 0.1 mL of test material in vehicle, and 0.1 mL of test material in 50:50 FCA/vehicle.
One week after intradermal injections, the same region was again shorn, and 0.3 mL of undiluted test material was applied via moistened filter paper under occlusive bandage and held in place for 48 hours.
Three weeks after the induction phase, the one flank of each animal was shorn, and 0.1 mL of diluted test material applied via filter paper and held in place by occlusive bandage for 24 hours. Reactions were read 24 and 48 hours after patch removal, and graded on a 4 point scale.
Challenge controls:
Water was used as a negative control
Positive control substance(s):
no
Positive control results:
not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 mL 50% dilution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 mL 50% dilution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 mL 50% dilution
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1 mL 50% dilution. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.

A study using such a formulation is considered relevant to use for this substance since such formulations represent 95% of the end use of this substance.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Brake FLuid DOT 4 Super is not sensitising
Executive summary:

Brake Fluid DOT 4 Super was tested for sensitisation in Guinea pigs using the Magnusson and Kligman assay. No evidence of sensitsation was observed, and the formulation was considered to be non-sensitising.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study conducted prior to GLP, but follows accepted guidelines and is well reported.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study does not need to be conducted because adequate reliable data is available from this alternative study providing data on the potential for skin sensitisation.
Species:
guinea pig
Strain:
other: P-strain
Sex:
male/female
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
5% for induction phase 1, undiluted for induction phase 2, and 50% challenge phase
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5% for induction phase 1, undiluted for induction phase 2, and 50% challenge phase
No. of animals per dose:
20 (test material); 10 (negative controls)
Details on study design:
Induction Phase:
Guinea pigs were shorn in the shoulder region and challenged in 2 rows of 3 intradermal injections each with 0.1 mL Freund's Complete Adjuvant, 5% Brake Fluid 500 DOT 4 in water, or 5% Brake Fluid 500 DOT 4 in 50:50 water: FCA. One week after the intradermal injections, the site was clipped free of hair and a soaked filter paper, covered with overlapping plastic adhesive tape and secured with an elastic bandage and left in place for 48 hours.

Challenge Phase:
Two weeks after topical induction, hair was removed from the site and test material was applied via soaked filter paper, covered with an adhesive tape, and held in place with an elastic bandage for 48 hours. Reactions were read at 24 and 48 hours.
Challenge controls:
Vehicle (water) was used as negative control
Positive control substance(s):
not required
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 19.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Brake Fluid 500 DOT 4 was non-sensitising to Guinea pig skin.
Executive summary:

Brake Fluid 500 DOT 4, a formulation containing primarily 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol in borated and non borated form, was tested for skin sensitisation using the Guinea pig Magnusson and Kligman method. No evidence of skin sensitisation was seen in the study.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
no
Remarks:
Prior to GLP
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study does not need to be conducted because adequate reliable data is available from this alternative study providing data on the potential for skin sensitisation.
Species:
guinea pig
Strain:
other: "P-strain"
Sex:
male/female
Details on test animals and environmental conditions:
Animal care details not provided in study report
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
1%
Route:
epicutaneous, open
Vehicle:
corn oil
Concentration / amount:
1%
No. of animals per dose:
20
Details on study design:
Guinea pigs (10/sex for the test material treated animals or 5/sex as controls), were administered the test substance as 1% in corn oil intradermally. Topical induction and challenge were done to test for immediate, 24 and 48 hours responses.
Challenge controls:
5/sex injected with corn oil only
Positive control substance(s):
no
Positive control results:
not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
one female died from injection site trauma
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: one female died from injection site trauma.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
corn oil only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: corn oil only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil only
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: corn oil only. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

A study using such a formulation is considered relevant to use for this substance since such formulations represent 95% of the end use of this substance

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Brake Fluid 500 DOT 4 was not sensitising in this Magnusson and Kligman guinea pig sensitisation assay.
Executive summary:

Guinea pigs (10/sex for the test material treated animals or 5/sex as controls), were administered the test substance Brake Fluid Dot 4,

a formulation containing primarily 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol in borated and non borated form, as 1% in corn oil intradermally. Topical induction and challenge were done to test for immediate, 24 and 48 hours responses. No evidence of sensitisation was observed.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5,8,11-tetraoxatridecan-13-ol; 2-[2-(2-methoxyethoxy)ethoxy]ethan-1-ol
EC Number:
915-389-0
Molecular formula:
C9H20O5 and C11H24O6
IUPAC Name:
2,5,8,11-tetraoxatridecan-13-ol; 2-[2-(2-methoxyethoxy)ethoxy]ethan-1-ol

Results and discussion

In vivo (non-LLNA)

Results
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion