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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2002-04-26 to 2002-09-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, chlorides
EC Number:
263-082-9
EC Name:
Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, chlorides
Cas Number:
61789-73-9
IUPAC Name:
61789-73-9

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A., (Como) and bred by P.O.A.D.A., Mandello Lario, (CO).
- Age at study initiation: 9 - 11 weeks of age.
- Weight at study initiation: approximately 2kg.
- Housing: Animals were individually housed in stainless steel cages measuring 48 x 63 x 41 cm and equipped with grid floors.
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: At least 10 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2°C
- Humidity (%): 55 °C 15 %
- Air changes (per hr): 15 to 20 air changes per hour
- Photoperiod: 12hrs dark / 12hrs light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: each animal served as its own control
Amount / concentration applied:
TEST MATERIAL
- Amount applied : 0.5g of the test material was reduced to paste with sterile water and spread over a gauze square measuring 2.5x2.5 cm.
Duration of treatment / exposure:
4 hour exposure period
Observation period:
60 min, 24, 48, 72 hrs and 7d, 14d after removal the patch.
Number of animals:
3 female animals.
Details on study design:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 2.5x2.5 cm
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: the treated site of each animal was cleaned by gentle swabbing of the skin with cotton wool soaked in water
- Time after start of exposure: 4 hours after the start of exposure.

SCORING SYSTEM: according to OECD guideline 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: On day 14 (end of the observation period) , a very slight erythema (grade 1) was still observed.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: On day 14 (end of the observation period) , the severe erythema (grade 4) was still present.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: On day 14 (end of the observation period) , a moderate erythema (grade 3) was still observed.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: On day 14 (end of the observation period) , a very slight oedema (grade 1) was still observed.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean of the 24, 48 and 72-hour readings
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: On day 14 (end of the observation period) , a very slight oedema (grade 1) was still observed.
Irritant / corrosive response data:
- 1 hour after the removal of the dressing, well defined erythema (score of 2) and very slight oedema (score of 1) were observed in all animals.
- After 24 hours and until day 7, a severe erythema (score of 4) was observed in all animals. The animals showed also necrotic areas of the superficial layers of the skin (stratum corneum) while the dermis was not included. Well defined oedema (score of 2) was noted at the 24, 48 and 72 hour examinations.
- At the end of the observation period (day 14), the superficial lesions had disappeared but very slight to severe erythema was still present. Very slight oedema (score of 1) was still present in 2 of the 3 animals at the 14 day examination.
For raw data see table 1 in the "remarks on results" freetext.
Other effects:
There was no indication of a systemic effect of treatment.
There were no changes in body weight during the course of the study.

Any other information on results incl. tables

Table 1 Individual skin irritation scores according to the OECD 404 guideline

Erythema

Oedema

Animal No

1

2

3

1

2

3

After
1 h

2

2

2

1

1

1

After 24 h

4

4

4

2

2

2

After 48 h

4

4

4

2

2

2

After 72 h

4

4

4

2

2

2

Mean score 24-72 h

4

2

Day 7

4

4

4

1

1

1

Day 14

1

4

3

0

1

1

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC
Conclusions:
The results of this study indicate that the test item has strong irritating effects when applied to the skin of rabbits and its effects are not fully reversible within the 14-day observation period. According to the criteria laid down in CLP (Reg 1272/2008/EC) and directive 67/548/EEC, the test material is therefore classified irritant Category 2 and irritant R38 respectively.
Executive summary:

The potential of the test material (containing 10 -15% isopropanol and 5% water to induce skin irritation was assessed in 3 rabbits according to the

OECD guideline 404 in compliance with the principles of Good Laboratory Practice regulations.

A single dose of 0.5 g of test material reduced to paste with sterile water was applied to the skin of the rabbits under a semi-occlusive dressing for a 4-hour exposure period. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing and then on days 7 and 14,in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

The mean scores over 24, 48 and 72 hours for individual animals were 4.0, 4.0, and 4.0 for erythema and 2.0, 2.0, and 2.0 for oedema. After 24 hours and until day 7, a severe erythema (score of 4) was observed in all animals. The animals showed also necrotic areas of the superficial layers of the skin (stratum corneum) while the dermis was not included. Well defined oedema (score of 2) was noted at the 24, 48 and 72 hour examinations. At the end of the observation period (day 14), the superficial lesions had disappeared but very slight to severe erythema was still present. Very slight oedema (score of 1) was still present in 2 of the 3 animals at the 14 day examination.

Even if the solvent Isopropanol probably enhances the uptake of the sustance,it does not interfere with the inherent toxicity of the substance itself which must be considered as a severe skin irritant.