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EC number: 907-996-4 | CAS number: -
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
No member of the glycol ether family shows any evidence of skin sensitisation potential. None of the functional groups present within the molecule (ether andhydroxyl, methyl and methylene group) are associated with skin sensitisation. Any substance within the family can therefore be used as a source of information to predict the toxicity of individual components or mixtures of components on the assumption there is no interaction between them..
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source: Monoethylene glycol butyl ether, Diethylene glycol butyl ether, Reaction mass of tri and tetraethylene glycol methyl ether.
Target: Multi-constituent substance of triethylene glycol butyl ether and tetraethylene glycol butyl ether.
Impurities: Both the source and target substances butyl series will contain the same impurities as they are produced in the same process, therefore they will have similar impurity profiles and impurities will not impact on the validity of the read across. The methyl series may contain lower and higher molecular weight members of the methyl series but these are not associated with skin sensitisation and will not invalidate the read across.
3. ANALOGUE APPROACH JUSTIFICATION
The members of the butyl series will provide information on the skin sensitisation potential of molecules containing -CH2CH2OH moieties and C4H9OCH2CH2 terminal molecular structures. The methyl series will provide information on the skin sensitisation potential of the tri and tetraethylene glycol structure (3 and 4 EO links with a terminal OH).
4. DATA MATRIX
monoethylene glycol butyl ether: not sensitising
diethylene glycol butyl ether: not sensitising
brake fluid containing 50% of a mixture of tri and tetraethylene glycol methyl ether and borated glycol ethers.: not sensitising
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:
- 1984
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Report of study available on a structurally related compound. Not to GLP and not as fully documented as ideally required but in sufficient detail to judge results as reliable. Rationale for using a read across substance is included in overall remarks section.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Remarks:
- , none noted
- Principles of method if other than guideline:
- Magnusson and Kligman. Followed company standard operating procedure 011/02.
- GLP compliance:
- not specified
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Reliable in vivo GPMT study already available.
- Species:
- guinea pig
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Weight at study initiation males: 320-360g. Weights at end: 424-490
- Weight at study initiation males: 340-350g. Weights at end: 402-480
- Diet: ad libitum RGP pellets, hay, cabbage
- Water: ad libitum
IN-LIFE DATES: From: 27.11.85 To: 2.1.85 - Route:
- intradermal
- Vehicle:
- physiological saline
- Concentration / amount:
- 2.5% for induction exposure but challenge exposure used undiluted.
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Concentration / amount:
- 2.5% for induction exposure but challenge exposure used undiluted.
- No. of animals per dose:
- 10
- Details on study design:
- RANGE FINDING TESTS
Preliminary experiments for the intradermal injection (4 females) established that 2.5% was the maximum concentration that could be tolerated without excessive irritation (odema). An occluded patch preliminary test established that epicutaneous occluded exposure to neat material could be tolerated without any adverse reaction.
MAIN STUDY
Sensitisation induced by intradermal injections of both test substance and Freund's Complete Adjuvant. The induction process was supplemented 6-7 days later by test substance applied to the shoulder injection sites under occlusion. 12-24 days later the animals were challenged by occluded patch. A further challenge was made one week later. Challenge patches were applied for 24hours and reaction sites examined at 24 and 48 hours - Challenge controls:
- 'Treated' negative controls used (all male) at both challege time points.
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- No evidence of sensitisation
- Executive summary:
A study was carried out which broadly followed the requirements of a guideline M&K skin sensitisation study on the substance 2 -(2 -butoxyethoxy)ethanol. No adverse skin sensitisation reactions were observed. Because of the structural similarity, this result can be reliably be read across to the substance 2 -(2 -(2 -butoxyethoxy)ethoxy)ethanol.
Synopsis
Not 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:
- 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: A GLP guideline study for which the full study report is available. No data on substance purity.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Adequate guinea pig maximisation study already available.
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Lab colony
- Initial weight: 300-331g
- Diet: RGP pellets, hay, cabbage ad libitum
- Water ad libitum
IN-LIFE DATES: From: 4/12/89 To: 11/1/90 - Route:
- intradermal and epicutaneous
- Vehicle:
- physiological saline
- Concentration / amount:
- Intradermal injections: 0.5%, epicutaneous induction exposure: 25%, challenge exposure: 10%
- Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Concentration / amount:
- Intradermal injections: 0.5%, epicutaneous induction exposure: 25%, challenge exposure: 10%
- No. of animals per dose:
- 10
- Details on study design:
- RANGE FINDING TESTS: Irritation test. Intradermal injections of concentrations in 0.9% saline and occluded patch irritation tests to establish non irritant concentrations. For intradermal injections, concentrations up to 0.5% only produced a faint pinkness. At 1% elevated reaction and/or odema occured. For the occluded patch irritancy test, 10% concentration produced no reaction, whereas 25% produced very faint erythema.
MAIN STUDY- intradermal injection followed one week later by occluded patch application.
A1. INDUCTION EXPOSURE - intradermal
- Site: dorsal shoulder area
- Preparation: clipped
- Concentrations: 0.5% in 0.9% saline, with and without 50% Freund's complete adjuvant. (FCA also injected alone.)
A2. INDUCTION EXPOSURE -occluded patch
- Exposure period: 48 hours
- Site: same 2x4cm dorsal shoulder area as above.
- Concentrations: FIlter paper saturated with 25% 2-butoxyethanol in 0.9% saline held in place with adhesive wrap.
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 13 and 20 days after second induction exposure.
- Exposure period: 24 hours
- Site: clipped and shaved flank
- Concentrations: 8mm diameter fileter paper patch in an 11mm dia aluminium test cup saturated with 10% 2-butoxyethanol in 0.9% saline held in place by adhesive plaster.
- Evaluation (hr after challenge): 24, 48hrs - Challenge controls:
- Yes. Controls treated subject to FCA intradermal injection and either first or second 2-butoxyethanol challenge exposure (4 animals for each.)
- Positive control substance(s):
- no
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Clinical observations:
- no adverse reactions seen
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: no adverse reactions seen.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Clinical observations:
- no adverse reactions seen
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: no adverse reactions seen.
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no adverse reactions seen
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no adverse reactions seen.
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no adverse reactions seen
- Remarks on result:
- other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no adverse reactions seen.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information
- Conclusions:
- Substance shows signs of skin irritancy but is not a skin sensitiser.
- Executive summary:
In a GLP study performed according to OECD guideline 406, 2 -butoxyethanol was tested in Guinea Pigs for sensitisation potential . Induction was performed with a dermal injection of 0.5 % 2 -butoxyethanol in 0.9 % saline and a topical application of a 25 % 2 -butoxyethanol in 0.9 % saline. Challenge was made with a topical application of 10 % 2 -butoxyethanol in saline. All topical applications were made occlusively. Concentrations tested were based on results found in preliminary studies (showing a Maximal Concentration with No Irritation (CMNI) of 10 %). Two challenge applications were made at one week interval.
No evidence of sensitisation was seen in treated animals both at challenge and re-challenge.
Synopsis: not 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted prior to GLP, but follows accepted guidelines and is well reported. Rationale for using a read across substance is included in overall remarks section.
- 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:
- Reliable in vivo GPMT study already available.
- 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
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 19.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. 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 was tested for skin sensitisation using the Guinea pig Magnusson and Kligman method. No evidence of skin sensitisation was seen in the study.
Data source
Materials and methods
- Justification for non-LLNA method:
- Existing in vivo studies available for read across purposes.
Test material
- Reference substance name:
- 2-(2-(2-butoxyethoxy)ethoxy)ethanol
- EC Number:
- 205-592-6
- EC Name:
- 2-(2-(2-butoxyethoxy)ethoxy)ethanol
- Cas Number:
- 143-22-6
- Molecular formula:
- C10H22O4
- IUPAC Name:
- 2-(2-(2-Butoxyethoxy)ethoxy)ethanol
- Reference substance name:
- 3,6,9,12-tetraoxahexadecan-1-ol
- EC Number:
- 216-322-1
- EC Name:
- 3,6,9,12-tetraoxahexadecan-1-ol
- Cas Number:
- 1559-34-8
- Molecular formula:
- C12H26O5
- IUPAC Name:
- 3,6,9,12-tetraoxahexadecan-1-ol
Constituent 1
Constituent 2
Results and discussion
In vivo (non-LLNA)
Results
- Remarks on result:
- no indication of skin sensitisation
- Remarks:
- These conclusions are as a result of extrapolation from the results of the source substance
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
