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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:
14 November 1990 - 12 December 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed under GLP and according to standard OECD guideline 404

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: Halamid
Appearance: white powder
Batch No.: 9520830
Purity: Technically pure, treated as 100% pure
Test substance storage: In the closed container at room temperature (keep cool) and in the dark
Stability under storage: Stable
Stability in vehicle: Stable for at least 96 hours in water

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: approximately 13 weeks
- Weight at study initiation: 2218 - 2479 grams
- Housing: individually in cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day.
- Water (e.g. ad libitum): ad libitum, automatic drinking system (ITL, Bergen, The Netherlands)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 November 1990 To: 12 December 1990

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: The contralateral flank was similarly prepared (but without test article and vehicle) to act as a procedural control.
Amount / concentration applied:
Concentration: 0.5 g
Duration of treatment / exposure:
4 hour(s)
Observation period:
14 days or 21 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2 x 3 cm
- % coverage: no data
- Type of wrap if used: On test day 1, 0.5 gram of the moistened test substance was applied to the intact skin of the shaved area on one flank, using a Metalline patch (2x3 cm, Lohman, Neuwied, W.-Germany) mounted to Micropore tape (3M, S t . Paul, U.S.A.). The contralateral flank was similarly prepared (but without test article and vehicle) to act as a procedural control. The dressing was wrapped around the abdomen and secured with an elastic bandage (Coban, 3M, S t . Paul, U.S.A.).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the remaining test article was removed using a tissue moistened with tap-water and subsequently a dry tissue.
- Time after start of exposure: 4 hours.

SCORING SYSTEM: According to Draize (1944)

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate t o severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

OEDEMA FORMATION
No oedema 0
Very slight oedema (barely perceptible) 1
Slight 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 area o f exposure) 4

Primary irritation index Degree of irritation
0 non-irritating
0.1-2.0 midly irritating
2.1-5.0 moderately irritaing
5.1-8.0 severely irritating

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Remarks:
Erythema/eschar and oedema
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
Yellow staining of the treated skin in 4 animals. No irritation in 2 animals, slight irritation which was reversible in 24 hours in another 2 animals, and corrosive effects of the skin in the remaining 2 animals. 
Other effects:
No systemic toxicity or mortality was observed.

Any other information on results incl. tables

no.

Effect

Hour

Days after application

Mean score erythema

24/48/72 h

Mean score oedema

24/48/72 h

1

1

2

3

7

14

21

354

Erythema/ eschar

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

355

Erythema/ eschar

Oedema

4

1

4

-

4

-

4

-

4

-

4

-

4

1

4

-

356

Erythema/ eschar

Oedema

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

368

Erythema/ eschar

Oedema

4

1

4

-

4

-

4

-

4

-

0

0

*

*

4

0

372

Erythema/ eschar

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

*

*

0

0

376

Erythema/ eschar

Oedema

1

0

0

0

0

0

0

0

0

0

0

0

*

*

0

0

Mean

1.1

0.7

0.7

0.7

0.7

0.7

0.8

- could not be determined due to crusts on the treated skin.
* after 14 days the study was stopped for this second group of animals

Applicant's summary and conclusion

Interpretation of results:
other: Skin Corr. 1B
Remarks:
according to the classification criteria outlined in Annex I and according to Annex VI of 1272/2008/EC (CLP).
Conclusions:
Tosylchloramide sodium, trihydrate resulted in an average overall irritation score of 0.7 ) when applied to the intact rabbit skin. However, according to the clinical judgement of the treated skin in two animals (corrosion). The substance is classified in catergory Skin Corr. 1B (H314: Causes severe skin burns and eye damage) according to the classification criteria outlined in Annex I and according to Annex VI of 1272/2008/EC (CLP).
Executive summary:

The purpose of this study was to assess the possible irritation or corrosion potential of Tosylchloramide sodium, trihydrate when a single dose was placed on the skin of rabbits. This study was carried out in accordance with OECD Guideline No. 404, "Acute Dermal Irritation/Corrosion and EEC Directive 84/449/EEC, Part B.4, "Acute Toxicity - Skin Irritation". Tosylchloramide sodium, trihydrate was applied on the shaved skin of six animals, using semi-occlusive dressings for 4 hours, followed by six (seven) observations at approximately 1, 24, 48 and 72 hours and 7 and 14 days (and 21 days for three animals only) after removal of the dressings and the remaining test substance. Under the conditions of this study, Tosylchloramide sodium, trihydrate resulted in no skin irritation in two animals, very s light oedema and/or very slight erythema in two other animals and eschar formation and slight oedema in the remaining two animals. The eschar formation and oedema noted in two animals were disappeared within 15 days in one of the two animals. Both animals showed scar tissue on each last observation day. The slight skin irritation noted in two animals was reversible within 24 hours, while the severe skin irritation in the other two animals was reversible within 15 days in one of these animals and not reversible within the study period (22 days) in the second animal. In the area of application, yellow staining of the treated skin by the test substance was observed in four of the six animals. Corrosive effects occurred on the skin in two of the six rabbits. No signs of systemic intoxication were observed during the study period. Tosylchloramide sodium, trihydrate resulted in an average overall irritation score of 0.7 ) when applied to the intact rabbit skin.

However, according to the clinical judgement of the treated skin in two animals (corrosion). The substance is classified in catergory Skin Corr. 1B (H314: Causes severe skin burns and eye damage) according to the classification criteria outlined in Annex I and according to Annex VI of 1272/2008/EC (CLP).