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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:
1990-05-15 to 1990-07-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study according OECD 406

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
For the maximisation test 3 groups were established per random: a test item group of 20 animals and 2 control groups of 10 animals each. Animals were used for two provocations (1. provocation after 7 weeks and a second provocation 24 h later). Control group 1 was used for the single 1. provocation test and control group 2 was used for the second provocation test.

The animals were initially exposed to the test substance by intradermal injection (55) and epidermal application (100%). following a rest period the animals were exposed to a challenge dose. the extend and degree of skin reaction to the challenge exposure in the test animals was compared with that demonstrated by control animals
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in the year 1990. At this time no valid OECD guideline for a LLNA was adopted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
content: 99.1%, clear, liquid substance

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Bor: DHPW
Sex:
male
Details on test animals and environmental conditions:
male guinea pigs, SPF, ca. 5-8 weeks old, average weight 376 g, husbandry: standardised conditions, 5 animals per cage (makrolon type IV)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: cremophor/physiol. saline
Concentration / amount:
100% (undiluted), 50%, and 10% (in Cremphor/physiol saline)
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
other: cremophor/physiol. saline
Concentration / amount:
100% (undiluted), 50%, and 10% (in Cremphor/physiol saline)
No. of animals per dose:
20 animals for the test item group, 10 animals each for the 1. + 2. control group
Details on study design:
RANGE FINDING TESTS: dose finding studies for intradermal and topical application were reported.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: single intradermal and topical
- Exposure period: one week after the intradermal exposure the topical exposure followed. after 3-4 weeks provocation was done
- Test groups: 20 animals
- Control group: 10 animals
- Site: back and flanks
- Frequency of applications: single
- Duration: indradermal induction 1 week , topical induction 3-4 weeks
- Concentrations: indradermal induction 5%, topical induction 100%


B. CHALLENGE EXPOSURE
- No. of exposures: 1. provocation includes the test item group and the 1. control group; 2. provocation includes the test item group and the 2. control group ¿ only one exposure
- Day(s) of challenge: 3-4 weeks after the intradermal induction
- Exposure period: 24 hours
- Test groups: 20 animals
- Control group: 10 animals
- Site: back and flanks
- Concentrations: 100, 50, 10 %
- Evaluation (hr after challenge): 48, 72 hours

Challenge controls:
2 control groups included; one group for 1. challange, second group for 2. challange
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 12.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10 or 50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 or 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
10 or 50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10 or 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 or 50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 or 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
10 or 50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 10 or 50 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Group:
positive control
Remarks on result:
other: see 'Overall remarks, attachments'

Any other information on results incl. tables

After the 1. challenge with pure (100%) test compound 12 out of 20 animals of the test group revealed skin effects (score 1: discrete/patchy erythema); the control group revealed no skin reactions. After a 2. challenge with 10 or 50% test compound no skin effects were observed.

Treatment was tolerated without systemic symptoms by all animals. No death occured and body weight gain of the test group was identical with the control group.

A pilot experiment was conducted to define the induction and challange concentrations. After intradermal application of 5% compound erythema and a white area arround the injection site was observed. After dermal treatment of 4 animals 3/4 guinea pigs showed score 1erythema (discrete/patchy erythema) indicating some irritation property of the compound. No erythema was observed when control animal were topicall challanged with 100% compound during the test.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

In a Guinea Pig Maximization Test conducted according to OECD TG 406 and GLP animals were dosed with irritating concentrations of the test compound (5% for intradermal injection and 100% for topical application). During challenge with the undiluted compound 12 out of 20 animals showed slight erythema (grade 1) after 48 hours and 2 out of there animals showed slight erythema still after 72 hours. The remaining 10 animals showed no effect any more after 72 h. In a second, subsequent, challenge with 10 or 50% compound after a 7 day rest, no skin effects were observed in animals from the test or control group. No skin reaction was observed in any control animal throughout the main experiment. In a pilot experiment before the main experiment pure compound (100%) was topically applied to 4 naïve guinea pigs to define the topical induction and challenge dose for the main experiment. 3 out of 4 guinea pigs showed scale 1 skin erythema reaction indicating that pure compound has some irritation potential in guinea pigs. Overall, the data indicate some dermal irritation and/or low dermal sensitization potential of the compound.