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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
24 Jul - 16 Aug 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions. No data given about the reliability check.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data given on reliability check
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht, Borchen, Germany
- Age at study initiation: approx. 5 weeks
- Diet: Altromin Haltungsdiät 3032 DK, Lage, Germany, ad libitum; with additive carrots
- Water: tap water with an additive of ascorbic acid (1 g/L), ad libitum
- Mean weight at study initiation: 415 g
- Housing: 2-3 animals in Makrolon type IV cages
- Acclimation period: 5 days
- date of delivery: July 19th, 1990

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Preliminary study:
Intracutaneous induction: 0.5, 1 and 2%
Epicutaneous induction and retreatment: 40, 50, 60 and 70%

Main study:
Intracutaneous induction: 0.5%
Epicutaneous induction: 40%
Challenge: 20%




Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Preliminary study:
Intracutaneous induction: 0.5, 1 and 2%
Epicutaneous induction and retreatment: 40, 50, 60 and 70%

Main study:
Intracutaneous induction: 0.5%
Epicutaneous induction: 40%
Challenge: 20%




No. of animals per dose:
Preliminary study: 2 animals

Main study:
Test group: 20 females
Control group: 10 females
Details on study design:
RANGE FINDING TESTS: Yes, evaluation of dermal effects was done by treating the animals with 0.5%, 1% or 2% for intracutaneous induction (injection of 0.1 mL into the shaved flank) and 40%, 50%, 60% or 70% for epicutaneous induction and retreatment of the test substance (0.08 g on the shaved flank) and observation of irritating effects 24 h and 48 h after treatment.
Intradermal: Minimal irritation at 0.5% of the test article
Dermal: Minimal irritation at 40%
Based on the results of the preliminary study the minimal irritating concentrations, 0.5% dilution of the test substance in paraffine oil was used for intradermal induction and 40% of the test substance was used for the epidermal induction exposure. A 20% test substance concentration was selected as maximally non-irritating for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single application (intradermal induction on Day 1) and 48 hours (epidermal induction on Day 7)
- Test groups: 1
Intradermal (double injections):
Injection 1: 0.1 mL 1:1 mixture (v/v) Freuds'complete adjuvant (FCA) in paraffin oil
Injection 2: 0.1 mL test substance with vehicle (paraffin oil) in concentration minimally irritating (5%)
Injection 3: 0.1 mL test substance in a 1:1 mixture (v/v) with FCA (final concentrations: test substance minimally irritating (5%), FCA 50%)
Epicutaneous: test substance (40%) with vehicle (paraffin oil)

- Control group: 1
Intradermal (double injections; the injections 1 and 3 were identical):
Injection 1 and 3: a 1:1 mixture (v/v) FCA in paraffin oil
Injection 2: only vehicle (paraffin oil)
Epicutaneous: vehicle (paraffin oil)

- Site: symmetrically on both sides of the spine and from cranial to cauda
- Frequency of applications: once
- Concentrations: intradermal: 0.5%, epicutaneous: 40%
- Other: An examination of the injections was performed 1 and 24 hours after treatment.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 22 (14 days after induction)
- Exposure period: 24 h
- Test groups: test substance and vehicle (paraffin oil)
- Control group: test substance and vehicle (paraffin oil)
- Site: One sheared flank
- Concentrations: 20% solution in paraffin oil
- Evaluation (hrs after the end of the challenge exposure): 24 and 48 h
- Other: 24 hrs after challenge application the application area was washed off with warm water
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
20%
No. with + reactions:
1
Total no. in group:
19
Clinical observations:
One animal died after first induction
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 20% . No with. + reactions: 1.0. Total no. in groups: 19.0. Clinical observations: One animal died after first induction.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
No
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 20%. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: No.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
20%
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
One animal died after first induction
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: One animal died after first induction.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
No
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 20%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: No.

Any other information on results incl. tables

Main study:

Intracutaneous induction: After one hour, weak effects were observed in 7 of 20 treated animals and none of the control animals. 24 h after treatment, 11 of 20 treated animals showed weak effekts and again none of the control animals.

Epicutaneous induction: After one hour, weak up to moderate skin reactions were observed in 16 of 19 treated animals (one died after exposure) and in 7 of 10 control animals. 24 h later mostly weak effects were observed in 10 treated animals and in 2 of the control animals.

Challenge readings - grades of skin reaction of individual animals

 

Animal No.

Intracut. induction

Epicut. induction

Challenge

1 h

24 h

1 h

24 h

24 h

48 h

Control Animals

27

0

0

1

0

1

0

28

0

0

1

0

1

0

29

0

0

1

0

0

0

30

0

0

1

0

0

0

31

0

0

0

0

1

0

32

0

0

2

1

0

0

33

0

0

1

1

1

0

34

0

0

0

0

1

1

35

0

0

0

0

0

0

36

0

0

1

0

0

0

Test Animals

1

0

0

2

1

0

0

2

1

0

2

0

0

0

3

0

1

1

0

0

0

4

1

1

1

1

0

0

5

1

1

1

0

0

0

6

0

1

1

0

0

0

7

1

1

0

0

0

0

8

0

0

1

1

0

0

9

1

1

-

-

-

-

10

0

0

1

0

0

0

11

0

0

0

0

0

0

12

0

1

2

1

0

0

13

0

0

0

0

0

0

14

0

0

0

0

0

0

15

1

0

0

0

0

0

16

0

1

2

2

1

0

17

0

0

1

1

0

0

18

0

1

2

2

0

0

19

0

1

0

0

0

0

20

1

0

1

1

0

0

One animal died after first exposure. No significant differences in the gain of body weight was observed between treatment and control group.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
CLP: not classified
DSD: not classified