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Administrative data

Description of key information

For both dermal and eye irritation/corrosion an old pre-GLP study is available. Although not performed according to the current guidelines, the results as presented are robust enough for adequate conclusions: Tosyl chloride needs irritating to skin and causes irreversible effects on the eye. This information is consistent with other studies reported in literature.

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was performed pre-GLP and according to a method similar to OECD404. But with the following deviations: - exposure period 24 hours - rabbit skin is exposed under occlusion - the test substance is not moistened to ensure optimal skin contact - the animal skin is exposed intact and abraded - it cannot be assessed if/when effects are reversible. Observation were made up to 72 hour after exposure. - no data on substance identity or composition. - no details on test animals and their accomodation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: U.S. FDA (Fed. Reg. 28 (119), 5582, 1963)
Principles of method if other than guideline:
- exposure period 24 hours
- rabbit skin is exposed under occlusion
- the test substance is not moistened to ensure optimal skin contact
- the animal skin is exposed intact and abraded
- it cannot be assessed if/when effects are reversible. Observation were made up to 72 hour after exposure.
- no details on test animals and their accomodation
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
Duration of treatment / exposure:
24 hours
Observation period:
The skin is evaluated 24 and 72 hours after the start of exposure.
Number of animals:
6 with intact and 6 with abraded skin
Details on study design:
TEST SITE
- Area of exposure: back of the animal
- % coverage: 2.5x2.5 cm
- Type of wrap if used: Surgical patch measuring 1 inch x 1 inch (2.5 x2.5 cm). The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none
- Time after start of exposure: not applicable


SCORING SYSTEM: Draize
Erythema and eschar formation
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation
0 No oedema
1 Very slight edema(barely perceptible)
2 Slight edema(edges of the area well defined by definite raising)
3 Moderate edema(raised approximately 1mm)
4 Severe edema( raised more than 1 mm and extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: intact + abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: intact + abraded skin
Irritant / corrosive response data:
after 24 hours: well-defined erythema, ischemia and slight edema
after 72 hours: well-defined erythema, ischemia and very slight or slight edema.

No difference was observed between intact and abraded skin

Results

Rabbit No and sex

Hours after instillation

Average 24-72 hours:

Intact

Rabbit No and sex

Hours after instillation

Average 24-72 hours:

Abraded

Site

24

72

24

72

7247

erythema

4

4

4

7241

4

4

4

oedema

2

1

1.5

2

1

1.5

7248

erythema

D

D

D

7242

D

D

4

oedema

D

D

D

D

D

1.5

7249

erythema

4

4

4

7243

4

4

4

oedema

2

1

1.5

2

1

1.5

7250

erythema

4

4

4

7244

4

4

4

oedema

2

1

1.5

2

1

1.5

7251

erythema

4

4

4

7245

4

4

4

oedema

2

1

1.5

2

2

2

7252

erythema

4

4

4

7246

4

4

4

oedema

2

1

1.5

2

1

1.5

D = dead

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The results show that the test substance is severely irritating. The test substance was not moistened so contact with the skin may not have been optimal, but this was certainly compensated by the occluded conditions and 24-hr contact time. Reversibility cannot be assessed but corrosion is not observed. Although this study has many deviations performing a new study is not warranted because it will not provide any new information. With this study it has been shown that the substance is a skin irritant and the substance is classified as such.
Executive summary:

The primary irritation of PTSC to the skin is measured by a occlusive patch-test technique on the abraded and intact skin of albino rabbits. The study was performed according to methods similar to OECD404. but with the following deviations:

- exposure period 24 hours

- rabbit skin is exposed under occlusion

- the test substance is not moistened to ensure optimal skin contact

- the animal skin is exposed intact and abraded

- it cannot be assessed if/when effects are reversible. Observation were made up to 72 hour after exposure.

- no details on test substance identity or composition

- no details on test animals and their accommodation

Twelve healthy adult New Zealand White albino rabbits are used . Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions. An amount of 0.5 g is placed on the skin under occlusion for 24 hours. The skin is evaluated 24 and 72 hours after the start of exposure. After 24 hours: well-defined erythema, ischemia and slight edema after 72 hours: well-defined erythema, ischemia and very slight or slight edema. No difference was observed between intact and abraded skin.

The results show that the test substance is severely irritating. The contact time is too long and under occlusion but the test substance was not moistened so contact with the skin may not have been optimal. Reversibility cannot be assessed but corrosion is not observed. Although this study has many deviations performing a new study is not warranted because it will not provide any new information. With this study it has been shown that the substance is a skin irritant and the substance is classified as such.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed according to a method similar to OECD 405 and pre-GLP. The study did not last for 21 days to study reversibility but this would also not be acceptable nowadays for animal welfare reasons. Therefore the study is given validity 4 otherwise it can be a validity 2.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: U.S. FDA (Fed. Reg. 28(119), 5582, 1963)
Principles of method if other than guideline:
The study did not last for 21 days to study reversibility but this would also not be acceptable nowadays for animal welfare reasons.
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as the control
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
One single dose is given
Observation period (in vivo):
The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material.
Number of animals or in vitro replicates:
1, due to the severity of the effects
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done
- Time after start of exposure: not applicable

SCORING SYSTEM: 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

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

TOOL USED TO ASSESS SCORE: Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes are examined in a dark room under ultraviolet illumination.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: At the observation after 7 days the degree of the effects has increased.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: At the observation after 7 days the degree of the effects has increased.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Could not be scored, conjunctivae ischemic or necrotic.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Moderate to complete corneal opacity, slight iritis, ischemia and necrosis of the conjunctivae and swelling with lids about half closed.

results:

Rabbit No and sex

Region of the eye

Hours after instillation

Average 24-48-72 hours

24

48

72

7(days)

19

Cornea

Degree of opacity

3

3

3

4

3

Iris

1

1

1

?

1

Conjunctivae

Redness

-

-

-

-

Chemosis

3

2

2

2

2.33

? iris not discernible

- conjunctivae ischemic or necrotic

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Ischemia and necrosis of the conjunctivae were observed. Other effects increased in severity over a 7 day period. The study did not last for 21 days but this would also not be acceptable nowadays for animal welfare reasons. Therefore the test substance is considered to cause irreversible effects on the eye according to GHS.
Executive summary:

A study was performed to access the eye irritancy of para toluenesulfochloride. The study was performed pre-GLP. The study is similar to OECD405. 0.1g of the test substance was instilled in the eye of one rabbit. The untreated eye served as the control. Observations were made after 24, 48, 72 hours and after 7 days. The test substance caused very severe ocular lesions: moderate to complete corneal opacity, slight iritis, ischemia and necrosis of the conjunctivae and swelling with lids about half closed which were increased at the 7 day observation. Therefore the test substance is considered to cause irreversible effects on the eye according to GHS.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are two old pre-GLP studies available for the evaluation of the primary irritation/corrosion of Tosyl chloride (p-Toluenesulfochloride; PTSC) of both skin and eyes.

 

Skin irritation/corrosion:

The primary irritation of Tosyl chloride (p-Toluenesulfochloride; PTSC) to the skin is measured by a occlusive patch-test technique on the abraded and intact skin of albino rabbits. The study was performed according to methods similar to OECD 404, but with some deviations: exposure period 24 hours; rabbit skin is exposed under occlusion; the test substance is not moistened to ensure optimal skin contact. It could not be assessed if/when effects are reversible, as observations were made only up to 72 hour after exposure. An amount of 0.5 g was placed on the intact and abraded skin of 12 adult New Zealand White albino rabbits under occlusion for 24 hours. The skin was evaluated 24 and 72 hours after the start of exposure.

After 24 hours: well-defined erythema, ischemia and slight oedema after 72 hours: well-defined erythema, ischemia and very slight or slight oedema. No difference was observed between intact and abraded skin.

The results show that the test substance is severely irritating. The test substance was not moistened and therefore contact with the skin may not have been optimal, but this was certainly compensated by the occluded conditions and 24-hr contact time. Additionally, in contact with water Tosyl chloride readily hydrolyses to toluene sulfonic acid and HCL which are both corrosive acids. Moistening would have resulted to more severe effects.

Reversibility of the irritation cannot be assessed as observations beyond 72 hours are lacking but corrosion was not observed. Although this study has many deviations performing a new study is not warranted because it will not provide any new information. With this study it has been shown that the substance is a skin irritant and the substance is classified as such.

These results are consistent with the severe ocular lesions that PTSC caused in the eye irritation study.

 

The information from the OECD SIDS on 4-methylbenzenesulfonyl chloride (PTSC) also confirms these results. In an OECD 404, GLP compliant study, 500 mg of the test material with about 0.1 mL of sterile distilled water was applied to the abraded and intact sites on the shaved backs of rabbits for 4 hours. The skin of animals was examined at 1, 24, 48 and 72 hours after removal of the patches followed by carefully washing exposed areas with warm water. Erythema, oedema, and scab were observed and their scores ranged from 2 to 3, and 1 to 3 for erythema and oedema, respectively. The substance was evaluated as irritating to skin. The moistening of the substance possibly resulted to a worst case evaluation following the hydrolisation of PTSC into to toluene sulfonic acid and HCL, both corrosive acids.

 

Eye irritation

A pre-GLP study was performed to access the eye irritancy of PTSC. The study is similar to OECD 405. 0.1g of the test substance was instilled in the eye of one rabbit. The untreated eye served as the control. Observations were made after 24, 48, 72 hours and after 7 days. The test substance caused very severe ocular lesions: moderate to complete corneal opacity, slight iritis, ischemia and necrosis of the conjunctivae and swelling with lids about half closed, which were increased at the 7 day observation. Therefore the test substance is considered to cause irreversible effects on the eye according to GHS.

 

Also these results on the eyes are confirmed with the information from the OECD SIDS on 4-methylbenzenesulfonyl chloride (PTSC). The dossier reports that a test was performed according to the FHSA protocol, in which the eyes were exposed for 24 hours then scored at 24, 48 and 72 hours after the exposure. In this test PTSC was found to induce corrosion and irritation on the eyes of New Zealand Albino Rabbits. Another study also showed that the test substance was irritating and corrosive to eyes of rabbits and their symptoms were similar to the key study.

 

 

Respiratory irritation:

Vp is 0.13 Pa at 20°C, and the respirable fraction (≤ 4 µm) of the crystalline solid is below 0,04%. Also likelihood of exposures by aerosols from the use of the substance is low (also taking into consideration the low water solubility of 3.1 g/L). Therefore, exposures can be expected to be minimal, and although PTSC is found irritating to skin, respiratory irritation is not likely to occur.

 

Justification classification:

Available data from different studies shows consistent results, indicating that PTSC is irritating, but not corrosive, to skin, leading to Category 2 irritant with H315: Causes skin irritation.

Studies on PTSC indicate it should be classified as Category1 Irreversible effects on the eye with H319: Causes serious eye damage.

There are no data that that would lead to consider respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:

Available proprietary study

Justification for selection of eye irritation endpoint:

Only study available

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Available data from different studies shows consistent results, indicating that PTSC is irritating, but not corrosive, to skin, leading to Category 2 irritant with H315: Causes skin irritation.

Studies on PTSC indicate it should be classified as Category1 Irreversible effects on the eye with H319: Causes serious eye damage.

There are no data that that lead to consider respiratory irritation.

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