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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:
experimental study
Adequacy of study:
key study
Study period:
July-Aug 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was performed according to OECD 406 guideline and in compliance with the GLP Regulations. One vehicle control animal died. However, the death of this animal was considered not to be related to treatment. This does not seem to have an impact on the reliability of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing according to the REACH Regulation. However, this test was performed before entry into force of the REACH Regulation.

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)
EC Number:
221-220-5
EC Name:
N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)
Cas Number:
3033-62-3
Molecular formula:
C8H20N2O
IUPAC Name:
{2-[2-(dimethylamino)ethoxy]ethyl}dimethylamine
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 6933-10-5
- Physical state: liquid
- Analytical purity: responsibility of the sponsor
- Stability under test conditions: no apparent change in the physical appearance of the test article during administration
- Storage condition of test material: responsibility of the sponsor

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Buckberg Lab Animals, Tomkins Cove, New York
- Weight at study initiation: assay: 304-400g; naive control-rechallenge: 489-962g
- Age at study initiation: 4 to 6 weeks
- Housing: individually in wire mesh cages
- Diet (e.g. ad libitum): purina guinea pig diet, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: July 1992 To: August 1992

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: 80% ethanol (induction) and acetone (challenge)
Concentration / amount:
0.3mL/dose
induction: 4.0% (v/v); challenge: 2.0% (v/v); rechallenge: 1.0% (v/v)
Challenge
Route:
epicutaneous, occlusive
Vehicle:
other: 80% ethanol (induction) and acetone (challenge)
Concentration / amount:
0.3mL/dose
induction: 4.0% (v/v); challenge: 2.0% (v/v); rechallenge: 1.0% (v/v)
No. of animals per dose:
dose range: 10 (5m, 5f); test article: 20 (10m, 10f); positive control: 5 (2m, 3f); negative control: 10 (5m, 5f); naive control during rechallenge: 4 (2m, 2f)
Details on study design:
RANGE FINDING TESTS:
10 animals (5m, 5f) were each exposed to 4 different concentrations of the test material in ethanol and/or acetone (1.0, 2.0, 4.0, 6.0, 8.0, 10, and 50%)
primary challenge responses were graded
Highest non-irritatting concentration = concentration that induced responses not exceeding 2 + and 2 0 grades in the group of 4 animals.
The dose chosen for induction: 4.0%
The dose chosen for challenge: 2.0%
The dose chosen for rechallenge: 1.0%


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5 (3 inductions, 1challenge, 1 rechallenge)
- Exposure period: -
- Test groups: test substance in vehicle (80% ethanol)
- Control group: vehicle only
- Site: L shoulder
- Frequency of applications: once a week
- Duration: 6 h
- Concentrations: 4.0%


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 30 and 37
- Exposure period: -
- Test groups: test substance in vehicle (acetone)
- Control group: vehicle only (left flank), test article (right flank)
- Site: naive site on left side
- Concentrations: 2.0% (challenge), 1.0% (rechallange)
- Evaluation (hr after challenge): 24 and 48h


OTHER:
Due to the irritation observed in the vehicle control animals at challenge, all test article-treated animals, along with an additional group of 4 naive animals were rechallenged at 1.0% (v/v) in acetone, 7 days following the primary challenge.
24h after challenge and rechallenge, all animals were depilated with Neet Cream Hair Remover (Whitehall Laboratories, Inc., New York). A minimum of 2h after depilation test sites were graded. The grading was repeated 24h later (48h grade)
All animals were euthanized by CO2 inhalation at study termination.
Challenge controls:
The negative control group was challenged with vehicle (acetone) on the left flank and test article on the right flank.
7 days after the primary challenge, all test article treated animals, along with an additional group of 4 naive guina pigs were rechallenged.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene

Results and discussion

Positive control results:
Sensitising effects observed in all 5 animals receiving the positive control article

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2.0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.3
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2.0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.1
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
1.0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.0
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1.0%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
severity= 0.0
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
severity= 3.0
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
severity= 2.8
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle (acetone)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
severity= 0.0
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle (acetone)
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
severity= 0.0
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.0%
No. with + reactions:
1
Total no. in group:
9
Clinical observations:
severity= 0.2
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.0%
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
severity= 0.1
Reading:
other: naive control
Hours after challenge:
24
Group:
negative control
Dose level:
1.0%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
severity= 0.0
Reading:
other: naive control
Hours after challenge:
48
Group:
negative control
Dose level:
1.0%
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
severity= 0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the assay, the test article induced at 4.0%, challenged at 2.0% and rechallenged at 1.0% did not cause delayed contact hypersensitivity in guinea pigs.