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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
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. Both are members of the butyl glycol ether homologous family
Target: Triethylene 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 source and target substances may be impurities of each other. Higher oligomers present will not affect the validity of the read across approach as they contain the same functional groups and molecular structures.

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.

4. DATA MATRIX
monoethylene glycol butyl ether: not sensitising
diethylene glycol butyl ether: not sensitising
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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:
reference to other study
Qualifier:
equivalent or similar to
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
Statistics:
not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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 group
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 group
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 group
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:
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:
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 group
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 group
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 group
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 group
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.

Data source

Materials and methods

Justification for non-LLNA method:
Existing in vivo studies available for read across purposes.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): 2-(2-(2-butoxy)ethoxy)ethanol
Analytical purity: purity 79.5%

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