Registration Dossier

Administrative data

Endpoint:
skin sensitisation, other
Remarks:
Data available from an in-vivo study performed before the requirement for an LLNA study..
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 04 to 29 Oct 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study run to a method comparable with current guidelines and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Batch No.: Not specified
Purity: Not specified

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: From D. Hall, Newchurch, Staffordshire, England
- Age at study initiation:
- Weight at study initiation: 457-580 g
- Housing: Be housed in suspended cages with wire mesh floors
- Diet (e.g. ad libitum): A vitamin C-enriched was given weekly
- Water (e.g. ad libitum): They had free access to tap water
- Acclimation period: 26 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 21℃
- Humidity (%): 30-70%
- Air changes (per hr): Approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light in each 24 hour period.

IN-LIFE DATES: From: 4 Oct 1988 To: 29 Oct 1988

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction interadermal injection: 0.05% v/v in distilled water
Induction topical application: 2.5% v/v in distilled water
Induction topical challenge: 1% and 0.5% v/v in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction interadermal injection: 0.05% v/v in distilled water
Induction topical application: 2.5% v/v in distilled water
Induction topical challenge: 1% and 0.5% v/v in distilled water
No. of animals per dose:
20 test animals
10 control animals
Details on study design:
RANGE FINDING TESTS: The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentration by the topical route of administration for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Once (injection) and once (topical)
- Exposure period: 48 hours
- Test groups: 20 females for intradermal injections and topical application
- Control group: 10 females for intradermal injections and topical application
- Site: Scapular region
- Frequency of applications: Topical followed one week after injection
- Duration: 21 days
- Concentrations:

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: 14 days
- Exposure period: 24 hours
- Test groups: 20 test animals
- Control group: 10 test animals
- Site: Left flank
- Concentrations: The test substance, 1% and 0.5% v/v in distilled water
- Evaluation (hr after challenge): The challenge sites were evaluated 24, 48, and 72 hours after removal of the patches.

OTHER:
Challenge controls:
The test and control animals were challenged topically two weeks after the induction period using the test substance, 1% and 0.5% v/v in distilled water.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% and 0.5% v/v
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
The dermal reactions were seen in five test animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% and 0.5% v/v. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: The dermal reactions were seen in five test animals.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% and 0.5% v/v
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No reactions were seen in all the ten animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% and 0.5% v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No reactions were seen in all the ten animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1% and 0.5% v/v
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
The dermal reactions were seen in five test animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% and 0.5% v/v. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: The dermal reactions were seen in five test animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1% and 0.5% v/v
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No reactions were seen in all the ten animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1% and 0.5% v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No reactions were seen in all the ten animals.
Reading:
rechallenge
Hours after challenge:
72
Group:
test group
Dose level:
1% and 0.5% v/v
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
The dermal reactions were seen in five test animals
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: test group. Dose level: 1% and 0.5% v/v. No with. + reactions: 5.0. Total no. in groups: 20.0. Clinical observations: The dermal reactions were seen in five test animals.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
1% and 0.5% v/v
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No reactions were seen in all the ten animals
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 1% and 0.5% v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No reactions were seen in all the ten animals.

Any other information on results incl. tables

Freund's treated controls:

Guinea-pig Number

E = Erythema

O = Oedema

Score

24 Hours

48 Hours

72 Hours

A

P

A

P

A

P

6580

E

0

0

0

0

0

0

O

0

0

0

0

0

0

6581

E

0

0

0

0

0

0

O

0

0

0

0

0

0

6582

E

L1

0

L1

0

L1

L1

O

0

0

0

0

0

0

6583

E

1

0

1

0

1

0

O

1

0

1

0

1

0

6584

E

L1

0

0

0

0

0

O

0

0

0

0

0

0

6585

E

1

0

1

0

1

0

O

1

0

1

0

1

0

6586

E

L1

L1

L1

0

L1

0

O

0

0

0

0

0

0

6587

E

0

0

0

0

0

0

O

0

0

0

0

0

0

6588

E

1

0

0

0

0

0

O

0

0

0

0

0

0

6589

E

0

1

0

0

0

0

O

0

0

0

0

0

0

L: Localised dermal reaction (restricted to a small area of the challenge site)

A: Anterior site, exposed to the test substance, 1% v/v in distilled water

P: Posterior site, exposed to the test substance, 0.5% v/v in distilled water

Test animals:

Guinea-pig

Number

E = Erythema

O = Oedema

Score

Results

Positive (+)

Negative (-)

Inconclusive(±)

24 Hours

48 Hours

72 Hours

A

P

A

P

A

P

6590

E

L1

0

L1

0

L1

0

-

O

0

0

0

0

0

0

6591

E

2NP

0

2NP

0

2NP

0

+

 

O

1

0

1

0

1

0

6592

E

1

0

1*

0

1*

0

-

O

0

0

0

0

0

0

6593

E

1

0

L1

0

L1

0

-

O

0

0

0

0

0

0

6594

E

2

2

2NP

2

2NP

1*

+

O

1

1

2

1

2

1

6595

E

2

0

1

0

1

0

-

O

1

0

1

0

1

0

6596

E

2NP

L1

2NP

L1

N

L1

+

O

2

0

2

0

3

0

6597

E

2

1

1

0

2

0

+

O

1

0

1

0

1

0

6598

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6599

E

2

0

2

0

2

0

±

O

0

0

0

0

0

0

6600

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6601

E

1

0

1

0

0

0

-

O

0

0

0

0

0

0

6602

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6603

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6604

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6605

E

L1

L1

L1

0

0

0

±

O

0

0

0

0

0

0

6606

E

2

2

1

0

1

1*

-

O

0

0

0

0

0

0

6607

E

0

L1

0

0

0

0

-

O

0

0

0

0

0

0

6608

E

0

0

0

0

0

0

-

O

0

0

0

0

0

0

6609

E

2

0

2NP

0

2NP

0

+

O

1

0

2

0

2

0

L: Localised dermal reaction (restricted to a small area of the challenge site)

*: Dryness and sloughing of the epidermis

NP: Necrotic patch

N: Necrosis

A: Anterior site, exposed to the test substance, 1% v/v in distilled water

P: Posterior site, exposed to the test substance, 0.5% v/v in distilled water

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this screening test, performed in twenty albino guinea-pigs, the test substance produced evidence of delayed contact hypersensitivity in five animals (25%). An inconclusive response was seen in the two animals. As this value is below the CLP criteria of 30%, this study does not trigger a positive classification.