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Administrative data

Description of key information

Skin corrosion (OECD TG 404): corrosive

Eye irritation (OECD TG 405): corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
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
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
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.

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

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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 November 1990 - 22 November 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test was performed under GLP and according to OECD 405 guideline.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands.
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2395 grams
- Housing: Individually in cages with perforated floors
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 g per day.
- Water (e.g. ad libitum): Free access to tap-water diluted with decalcified water.
- Acclimation period: At least five days before start of treatment under test conditions

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

IN-LIFE DATES: 19 November 1990 - 22 November 1990
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g
Duration of treatment / exposure:
72 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: According to Draize
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

Discharge
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs a considerable area around the eye

TOOL USED TO ASSESS SCORE: hand-slit lamp

On day 1, prior to test substance administration, the animal was physically examined and the eyes found to be normal. The test substance (approx. 100 mg per animal) was instilled in the conjunctival sac of the left eye of the animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24 hours observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was applied to both eyes of the animal to quantitatively examine the potential for corneal injury. This procedure was repeated on day 4. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Viability/Mortality; Daily, animal was also examined For signs of toxicity.
Body Weights: Day 1 of test (application day).
Symptoms: The eyes of the animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The corrosive properties of the test substance were described and recorded.
Irritation parameter:
overall irritation score
Remarks:
Cornea/iris/conjuctivae (excluding area and discharge not relevant for C&L)
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Due to the severity fo the effects the study was terminated after 72 hours
Irritant / corrosive response data:
Instillation of HALAMID into one of the eyes of animal 351 affected the cornea, iris and conjunctivae. The eye effects consisted of severe corneal opacity and severe conjunctival redness and chemosis. Effects on the iris could not be observed after day 1, due to the severe corneal opacity. Therefore the study was terminated on day 4. No further animals were treated.
Treatment of the eyes with 2% fluorescein, 24 and 72 hours after test substance instillation revealed corneal epithelial damage in animal 351. There was clear evidence of ocular corrosion.
Other effects:
No toxic symptoms were observed in the animal during the test period and no mortality occurred.

Rabbit No and sex

Region of the eye

Hours after instillation

Average 24-48 hours

1

24

48

72

3068 f

Cornea

Degree of opacity

3

4

4

4

4

Area of opacity

2

2

2

2

2

Iris

1

-

-

-

-

Conjunctivae

Redness

3

3

3

3

3

Chemosis

3

3

3

3

3

Discharge

0

0

1

3

1.3

* Due to the severity of the effects the study was terminated after 72 hours.

1 Iris could be scored for only approx. 25%, therefore no pupil reaction to light could be assessed.  Lacrimation was observed. Grey/white discolouration of the conjunctivae.

24 Iris could not be scored due to corneal opacity.  Lacrimation was observed. Grey/white discolouration of the conjunctivae. Fluor. area 100%.

48 Iris could not be scored due to corneal opacity.  Lacrimation was observed. Grey/white discolouration of the conjunctivae.

72 Iris could not be scored due to corneal opacity.  Grey/white discolouration of the conjunctivae. Fluor. area 100%.

Conjunctival redness and chemosis were also observed on the outside of the eyelids on days 2, 3 and 4.

Interpretation of results:
other: Eye Dam. 1
Remarks:
according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP)
Conclusions:
Due to the severity of the effects observed in one eye of the test animal the test substance is classified as Eye Dam. category 1 (irreversible effects on the eye) according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).
Executive summary:

The purpose of this study was to assess the possible irritation or corrosion potential when a single dose of Tosylchloramide sodium, trihydrate was placed i n the conjunctival sac of a rabbit eye. This study was carried out in accordance with OECD Guideline No. 405, "Acute Eye Irritation/Corrosion" and EEC Directive 84/449/EEC, Part B.5, Acute Toxicity - Eye Irritation. Tosylchloramide sodium, trihydrate was instilled in one of the eyes of one animal, followed by four observations at approximately 1, 24, 48 and 72 hours after test article administration. Only one animal was used, due to the irritancy obtained in the skin irritation study and the animal in this eye irritation study. Under the conditions of this study, Tosylchloramide sodium, trihydrate resulted in adverse effects of the cornea, iris and the conjunctivae. The eye effects consisted of severe corneal opacity and severe conjunctival redness and chemosis. Effects on the iris could not be observed after day 1, due to the corneal opacity. Therefore the study was terminated on day 4. No further animals were treated. Clear ocular corrosion was observed in the single animal. No signs of systemic intoxication were observed during the study period.

Due to the severity of the effects observed in one eye of the test animal the test substance is classified as Eye Dam. category 1 (H318 Causes serious eye damage ) according to according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin corrosion / irritation (OECD TG 404)

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, trihydrateE 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 1B according to the criteria outlined in Annex I and Annex VI of the CLP Regulation (1272 /2008/EC).

 

Eye irritation (OECD TG 405)

The purpose of this study was to assess the possible irritation or corrosion potential when a single dose of Tosylchloramide sodium, trihydrate was placed i n the conjunctival sac of a rabbit eye. This study was carried out in accordance with OECD Guideline No. 405, "Acute Eye Irritation/Corrosion" and EEC Directive 84/449/EEC, Part B.5, Acute Toxicity - Eye Irritation. Tosylchloramide sodium, trihydrate was instilled in one of the eyes of one animal, followed by four observations at approximately 1, 24, 48 and 72 hours after test article administration. Only one animal was used, due to the irritancy obtained in the skin irritation study and the animal in this eye irritation study. Under the conditions of this study, Tosylchloramide sodium, trihydrate resulted in adverse effects of the cornea, iris and the conjunctivae. The eye effects consisted of severe corneal opacity and severe conjunctival redness and chemosis. Effects on the iris could not be observed after day 1, due to the corneal opacity. Therefore the study was terminated on day 4. No further animals were treated. Clear ocular corrosion was observed in the single animal. No signs of systemic intoxication were observed during the study period. Due to the severity of the effects observed in one eye of the test animal the test substance is classified in catergory 1 (irreversible effects on the eye) according to the criteria outlined in Annex I and Annex VI of the CLP Regulation (1272 /2008/EC).

Justification for classification or non-classification

Based on the available information, Tosylchloramide sodium needs to be classified for Skin and Eye corrosion/irritation (Skin Corr. category 1B and Eye Dam. category 1 / H314 Causes severe skin burns and eye damage) in accordance with the criteria outlined in Annex I and Annex VI of the CLP Regulation (1272 /2008/EC).