Registration Dossier

Administrative data

Description of key information

A delayed contact hypersensitivity study (Kynoch, 1989) is available which is key study. This study showed that the test substance is not sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
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
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
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
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.

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

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A delayed contact hypersensitivity study was conducted according to OECD 406 guideline using guinea-pig (Kynoch, 1989). Key study. 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. In addition, two separate patch tests on human volunteers did not result in significant positive allergic responses.


Justification for classification or non-classification

Skin sensitisation: a delayed contact hypersensitivity study showed the test substance is a weak sensitizer, and no sensitization occurred in human patch tests. Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.4.2 the substance is not classified for this skin sensitisation endpoint. However, under the harmonized classification, index: 613 -099 -00 -6, 1-dodecyl-2-pyrrolidone is classified as Skin Sens. cat. 1.