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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:
Jan - March 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Purity not given. Study was performed according to OECD 406 guideline and in compliance with the GLP Regulations. It is not clear whether 8 or 10 animals were used in the dose-range finding study. It is not clear whether challenge was performed 13 or 14 days after the last induction period. However, it is unlikely that this will have an impact on the outcome of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Test has been performed 1991, before the regulation has been revised with respect to deviation from the LLNA as "gold standard"

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(2-aminoethoxy)ethanol
EC Number:
213-195-4
EC Name:
2-(2-aminoethoxy)ethanol
Cas Number:
929-06-6
Molecular formula:
C4H11NO2
IUPAC Name:
2-(2-aminoethoxy)ethan-1-ol

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: 300-700g
- Housing: individually in stainless steel 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): 20 ± 3°C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: Jan 1991 To: March 1991

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: ethanol
Concentration / amount:
10 %
Day(s)/duration:
0
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, semiocclusive
Vehicle:
other: ethanol
Concentration / amount:
10 %
Day(s)/duration:
7
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
other: no data
Vehicle:
other: ethanol
Concentration / amount:
10 %
Day(s)/duration:
14
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
other: ethanol
Concentration / amount:
10 %
Day(s)/duration:
29
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, semiocclusive
Vehicle:
other: ethanol
Concentration / amount:
10 %
Day(s)/duration:
36
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
dose range: 8 or 10 (unclear)
test article: 20 (10 male, 10 female)
positive control: 5
negative control: 10
Details on study design:
RANGE FINDING TESTS:
10 unexposed animals (5male/5female) are exposed to 4 different concentrations of the test material: 80% ethanol as the vehicle.
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, challenge and rechallenge : 10%


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 (80% ethanol)
- Site: L shoulder
- Frequency of applications: once a week
- Duration: 6 h
- Concentrations: 10%


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 28 (or 29) and 35 (or 36) (unclear)
- Exposure period: -
- Test groups: test substance in vehicle
- Control group: vehicle only (left flank), test article (right flank)
- Site: naive site on left side
- Concentrations: 10%
- Evaluation (hr after challenge): 24 and 48h


OTHER: 24h after challenge, 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).
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB)

Results and discussion

Positive control results:
Sensitising effects are observed in all 5 animals of the positive control group.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.3
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.2
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.3
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.2
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3 % DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Remarks:
Severity: 3.0
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3 % DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Remarks:
Severity: 2.6
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 % acetone
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.0
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 % acetone
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.0
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenged with 10% test substance
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.2
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenged with 10% test substance
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Severity: 0.2

Any other information on results incl. tables

Primary challenges were carried out after 14 days, 1 positive response was observed after 24 and 48 hours in the 10% DGA group. 7 days after the primary challenge, all test article treated animals were rechallenged at 10% concentration. 2 positive responses were observed after 24 and 48 hours after this rechallenge. After initial challenge a positive response was observed in all animals receiving the DNCB positive control. Erythema observed at 24 and 48 hours in 3 of negative control group at initial challenge.

Under EU criteria, the product is not classed as a sensitizer as it indicates a maximum (at rechallenge) of 10% positive (2/20) responses. A minimum figure of 15% under any study would be necessary for classification as a sensitizer with R43 under EU 18th ATP of the DSD. Practical experience over 20 years of manufacturing this product adds weight to this conclusion.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was determined to be not skin sensitizing in a Buehler test.
Executive summary:

In two preliminary dose-range-finding studies, ten animals (five males and five females) were each exposed to four different concentrations of the test substance in either 80% ethanol or acetone, to determine the highest non-irritating dose.


Based upon the results of the dose-range-finding studies, the test article was dosed at a 10% concentration. In order to determine if the test article is capable of causing delayed contact hypersensitivity, the test substance, was dermally applied to twenty guinea pigs (ten males and ten females) for a total of three six hour insult periods. Another group of five guinea pigs (three males and two females) was treated with 1-chloro-2,4-dinitrobenzene at a 0.3% concentration for a total of three six-hour insult periods. An additional group of ten guinea pigs (five males and five females) was treated with vehicle (80% ethanol) for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site.


A positive response was elicited in the animals receiving the positive control article, 1-chloro- 2, 4-dinitrobenzene (DNCB). Slight patchy erythema was observed at 24 and 48 hours in three of the negative control animals challenged with the test article at a 10% concentration. One positive response was observed at 24 and 48 hours after challenge in the test article-treated group. No responses were observed in the negative control animals challenged with the vehicle (acetone).


Seven days following the primary challenge, all test article treated animals were rechallenged at a naive site at a 10% concentration. Two positive responses were observed at 24 and 48 hours after rechallenge.


Based upon the observations made in the Delayed Contact Hypersensitivity Study in Guinea Pigs, the test substance induced, challenged and rechallenged at a 10% concentration did not cause delayed contact hypersensitivity in guinea pigs.