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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From 10 August, 1982 to 04 September, 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across study hence maximum reliability rating of 2 assigned according to ECHA guidance, although the study was conducted according to the method similar to the OECD guideline 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Querton 12 Br (Lauryl trimethyl ammonium bromide)
- Physical state: White powder
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire
- Age at study initiation: 4-6 wk
- Weight at study initiation: 357-450 g
- Diet: Vitamin C enriched Guinea pig diet F.D.I. (Special Diets Services Limited); ad libitum
- Water: Tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30-70%
- Air changes (per h): 15
- Photoperiod (dark / light): 12 h/12 h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: Intradermal injection- 0.01% w/w in water for injection, topical application- 0.5% w/w in distilled water
Challenge: 0.05% and 0.01% w/w in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: Intradermal injection- 0.01% w/w in water for injection, topical application- 0.5% w/w in distilled water
Challenge: 0.05% and 0.01% w/w in distilled water
No. of animals per dose:
15
Details on study design:
RANGE FINDING TESTS: The intradermal and topical irritancy of a range of aqueous dilutions of test substance was investigated to identify the following:
- irritant concentrations of the test substance suitable for the induction phase of the main study
- non-irritant concentration by the topical route of administration for the challenge phase

MAIN STUDY

A. INDUCTION EXPOSURE
- No. of exposures: Intradermal injections - three, topical application - once
- Exposure period: 48 h (topical application)
- Test groups: Intradermal injections - 4 X 6 cm2 area of dorsal skin on the scapular region of the animals was clipped free of hair with electric clippers. Three pairs of intradermal injections were made simultaneously into this area. Injectables were prepared as follows:
1. Freund's complete adjuvant was diluted with an equal volume of water for injection
2. Test substance, 0.01% w/w in water for injection
3. Test substance, 0.01% w/w in a 50:50 mixture of Freund's complete adjuvant and water for injection.

Topical application - One wk after the injections, the same 4 X 6 cm2 interscapular area was clipped and shaved free of hair. A 2 X 4 cm2 patch of Whatman No. 3 paper was saturated with test substance, 0.5% w/w in distilled water. The patch was placed on the skin and covered by a length of impermeable plastic adhesive tape (5 cm width "Blenderm"). This, in turn, was firmly secured by elastic adhesive bandage ("Elastoplast" 5 cm width) wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 h.

- Control group: During the induction period the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Exposure period: 24 h
- Test groups: The animals were challenged topically two wk after the induction period using test substance, 0.05% and 0.01% w/w in distilled water. Hair was removed by clipping and then shaving from the left flank of each animal. A 2 X 2 cm2 Whatman No. 3 paper was saturated with approximately 0.2 mL of the test substance in a similar fashion to that used for the topical induction application. The patch was sealed to the flank for 24 h under a 5 cm strip of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
- Control group: The animals of the control group were similarly challenged.
- Site: Left flank
- Concentrations: 0.05% and 0.01% w/w in distilled water
- Evaluation (h after challenge): 24, 48 and 72 h

OTHER: Scoring system:
Erythema and eschar formation:
No erythema: 0
Slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation:
No oedema: 0
Slight oedema (barely perceptible): 1
Well-defined oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4
Challenge controls:
The animals were challenged 2 wk after the induction period.
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:
0.05% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.05% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.05% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.05% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
0.05% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.05% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.01% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.01% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0.01% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
0.01% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.01% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.05% w/w
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
Localised dermal reaction restricted to a small area of the challenge site
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.05% w/w. No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: Localised dermal reaction restricted to a small area of the challenge site .
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.05% w/w
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
Localised dermal reaction restricted to a small area of the challenge site
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.05% w/w. No with. + reactions: 1.0. Total no. in groups: 15.0. Clinical observations: Localised dermal reaction restricted to a small area of the challenge site .
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.05% w/w
No. with + reactions:
0
Total no. in group:
15
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.05% w/w. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.

Any other information on results incl. tables

a) Dermal reactions elicited by challenge application in the test animals:

Guinea-pig number

E = Erythema

O = Oedema

Score

Results

Positive (+)

Negative (-)

24 h

48 h

72 h

A

P

A

P

A

P

620

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

621

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

622

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

623

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

624

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

625

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

626

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

627

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

628

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

629

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

730

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

731

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

732

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

733

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

734

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

b) Dermal reactions elicited by challenge application in the Freund's treated controls:

Guinea-pig number

E = Erythema

O = Oedema

Score

Results

Positive (+)

Negative (-)

24 h

48 h

72 h

A

P

A

P

A

P

630

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

631

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

632

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

633

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

634

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

635

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

636

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

637

E

O

0

0

1L

0

0

0

1L

0

0

0

0

0

-

638

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

639

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

735

E

O

1L

0

0

0

0

0

0

0

0

0

0

0

-

736

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

737

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

738

E

O

0

0

0

0

1L

0

0

0

0

0

0

0

-

739

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

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

A = Anterior site, exposed to test substance, 0.05% w/w in distilled water

P = Posterior site, exposed to test substance, 0.01% w/w in distilled water

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, test substance did not show any evidence of delayed contact hypersensitivity in guinea pigs.
Executive summary:

A guinea pig maximisation test was performed to determine the delayed contact hypersensitivity potential of structurally similar substance lauryl trimethyl ammonium bromide in thirty male albino guinea pigs. Doses were determined on the basis of preliminary investigations. Induction exposure: Intradermal injections- three pairs of intradermal injections (Freund's complete adjuvant diluted with an equal volume of water for injection, 0.01% w/w test substance in water for injection, and 0.01% w/w test substance in a 50:50 mixture of Freund's complete adjuvant and water for injection) were made simultaneously in the 4 x 6 cm area of dorsal skin on the scapular region of the animals. Topical application- one week after the injections, a 2 x 4 cm occlusive patch (0.5% w/w in distilled water) was placed on the skin and left for 48 hours. Challenge exposure: two weeks after the induction period using 0.05% and 0.01% w/w of test substance in distilled water. A 2 x 2 cm occlusive patch with approximately 0.2 mL of the test sample was applied. The challenge sites were evaluated after 24, 48 and 72 hours of patch removal. No dermal reactions were seen in any of the test animals during the observation period. Under the test conditions, the test substance did not show any evidence of delayed contact hypersensitivity in guinea pigs (Liggett and Seaber, 1982).