Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Studycomparable to OECD guideline 406 with acceptable restrictions. Not GLP but a statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was included in the report. No positive control included in the assay. It has to be noted that 3 readings instead of 2 were performed.

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:
no
Remarks:
but a statement that the report and the study were audited by the Quality Assurance unit is included.
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Querton 442

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 weeks
- Weight at study initiation: 400± 50 g
- Housing: in suspended cages with wire mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

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


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Main study:
-Induction:
intradermal injection: 0.1% v/v in water for injection.
topical application: 10% v/v in distilled water.
-Challenge:
2.5% and 1% v/v in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Main study:
-Induction:
intradermal injection: 0.1% v/v in water for injection.
topical application: 10% v/v in distilled water.
-Challenge:
2.5% and 1% v/v in distilled water
No. of animals per dose:
Test group of 15 animals and a control group of 15 in the main study.
Details on study design:
RANGE FINDING TESTS:
A preliminary study was conducted to determine the intradermal and topical irritancy of a range of aqueous solutions of Querton 442 (results are not included in the report).
MAIN STUDY

A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 epicutaneous
- Exposure period: epicutaneous: 48 hours

-> TEST GROUPS:
Intradermal exposure
Three injections of 0.1 mL were injected into each side of the animal as follows:
. Freund's complete adjuvant (FCA) diluted to 50% with water for injection
. TS at 0.1% w/v in vehicle
. TS at 0.1% w/v in a 50/50 (v/v) mixture of FCA and water for injection

Epicutaneous exposure
Application of 2 x 4cm patch saturated with the TS at 10% w/v in distilled water applied to the scapular region and held in place for 48 hours using an occlusive dressing.

-> CONTROL GROUP:
Intradermal exposure
Three injections of 0.1 mL were injected into each side of the animal as follows:
. Freund's complete adjuvant (FCA) diluted to 50% with water for injection
. vehicle
. A mixture 50/50 (v/v) FCA diluted to 50% with water for injection, and vehicle

Epicutaneous exposure
Application of 2 x 4cm patch saturated with the vehicule applied to the scapular region and held in place for 48 hours using an occlusive dressing.

- Site:
Intradermal exposure
6 injections in the clipped area (4 x 6 cm) in the scapular region

Epicutaneous exposure
4 x 6 cm area over the scapulae

- Frequency of applications:
One intradermal injection and one epicutaneous application 8 days after on the same site.

- Duration:
Epicutaneous exposure: 48 hours

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours

-> TEST GROUPS:
0.2 mL of the TS at 2.5% w/v in distilled water on the anterior left flank and 0.2 mL of the TS at 1% w/v in vehicule to a second site on the posterior left flank (occlusive epicutaneous application)

-> CONTROL GROUPS:
Same treatment as test group
- Site: anterior and posterior left flank

- Evaluation (hr after challenge): 24 , 48 hours and 72 hours after removal of the dressing according to the method of Draize.

Challenge controls:
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.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
4 and 3 animals with erythema grade 1 and 2 respectively.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 7.0. Total no. in groups: 15.0. Clinical observations: 4 and 3 animals with erythema grade 1 and 2 respectively..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
4
Total no. in group:
15
Clinical observations:
1 and 3 animals with erythema grade 1 and 2 respectively. One animal with erythema grade 2 showed also oedema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 4.0. Total no. in groups: 15.0. Clinical observations: 1 and 3 animals with erythema grade 1 and 2 respectively. One animal with erythema grade 2 showed also oedema grade 1..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
1 and 2 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: 1 and 2 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2..
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
10
Total no. in group:
15
Clinical observations:
6 and 4 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 10.0. Total no. in groups: 15.0. Clinical observations: 6 and 4 animals with erythema grade 1 and 2 respectively. 1animal with erythema grade 2 showed also oedema grade 2..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
7
Total no. in group:
15
Clinical observations:
4 and 3 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other).
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 7.0. Total no. in groups: 15.0. Clinical observations: 4 and 3 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other)..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
challenged with test substance 2.5% v/v in distilled water
No. with + reactions:
5
Total no. in group:
15
Clinical observations:
3 and 2 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other).
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: challenged with test substance 2.5% v/v in distilled water. No with. + reactions: 5.0. Total no. in groups: 15.0. Clinical observations: 3 and 2 animals with erythema grade 1 and 2 respectively. 2 animals with erythema grade 2 showed also oedema (grade 2 for one and grade 1 for the other)..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
1 animal with erythema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 1.0. Total no. in groups: 15.0. Clinical observations: 1 animal with erythema grade 1..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 15.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
0
Total no. in group:
15
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 0.0. Total no. in groups: 15.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
3
Total no. in group:
15
Clinical observations:
2 and 1 animals with erythema grade 1 and 2 respectively.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 3.0. Total no. in groups: 15.0. Clinical observations: 2 and 1 animals with erythema grade 1 and 2 respectively..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenged with test substance 1% v/v in distilled water
No. with + reactions:
2
Total no. in group:
15
Clinical observations:
2 animals with erythema grade 1.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenged with test substance 1% v/v in distilled water. No with. + reactions: 2.0. Total no. in groups: 15.0. Clinical observations: 2 animals with erythema grade 1..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
2 and 1 animals with erythema grade 1 and 2 respectively.
No. with + reactions:
1
Total no. in group:
15
Clinical observations:
1 animal with erythema grade 2.
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2 and 1 animals with erythema grade 1 and 2 respectively.. No with. + reactions: 1.0. Total no. in groups: 15.0. Clinical observations: 1 animal with erythema grade 2..

Any other information on results incl. tables

The dermal reactions observed in the test animals were considered to be similar to or less marked than the maximum reaction observed in animals of the control group. Some localised dermal reactions were observed, and dryness and sloughing of the epidermis.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the experimental conditions of this study and according to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the substance does not induce delayed contact hypersensitivity and is not classified.
Executive summary:

The potential of the substance to induce delayed contact hypersensitivity was assessed in guinea pigs using the technical grade dihydrogenatedtallowdimethylammonium chloride (78% active in isopropanol/water). The study was performed according to a method equivalent to the OECD guideline 406 and a statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was provided.

The induction phase was realized both by intradermal route on day 1 (Test substance 0.1 % v/v in water for injection) and by cutaneous route on day 8 (Test substance 10% v/v in distilled water ) in 2 groups of guinea pigs: 15 males for control group and 15 males for treated group. The challenge phase was realized on day 22 by cutaneous application of the test substance at 2.5% and 1% v/v in distilled water on two sites on the left flank . the cutaneous reactions were scored 24 ,48 and 72 hours after the challenge phase.

After the challenge application with 2.5 % v/v of the test substance in distilled water, erythema grade 1 or 2 were observed in 7, 4 and 3 controls animals at the 24, 48 and 72-hours readings respectively. 1 control animal showed also oedema. In the treated group, the incidence and severitiy of the cutaneous reactions were quite similar: 10, 7 and 5 treated animals showed erythema grade 1 or 2 at the 24, 48 and 72-hours readings. 2 treated animals showed oedema.

After the challenge application with 1% v/v of the test substance, an erythema ( grade 1 or 2) was observed in 3 ,2 and 1 out the 15 animals of the treated group at the 24, 48 and 72-hour readings respectively. In the control group, 1animal showed an erythema grade 1at the 24 -hour reading.

The persistent cutaneous reactions observed in 3/15 animals of the treated group after the challenge application may be attributable to delayed contact hypersensitivity but as the cutaneous reactions were more confined to the 24 hour examination, they were more consistent with irritation than delayed contact hypersensitivity.

Therefore, the cutaneous reactions observed in 3/15 animals (20%) of the treated groups were considered as irritative response and the substance was not considered as a skin sensitiser.