Registration Dossier

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 regarding classification: p-Toluenesulfonamide does not need to be classified for dermal or eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
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: This study was performed pre-GLP. Alike OECD 404, but with some deviations.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
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 (6 animals) and abraded (6 animals)
- 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 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:
other: 24-72 hours
Score:
0.3
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:
other: 24-72 hours
Score:
0
Max. score:
4
Remarks on result:
other: intact + abraded skin
Irritant / corrosive response data:
after 24 hours: Highest score: very slight erythema, no oedema
after 72 hours: Highest score: very slight erythema, no oedema

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

1

0

0.5

7241

0

0

0

oedema

0

0

0

0

0

0

7248

erythema

D

D

D

7242

1

0

0.5

oedema

D

D

D

0

0

0

7249

erythema

0

0

0

7243

1

0

0.5

oedema

0

0

0

0

0

0

7250

erythema

0

0

0

7244

1

0

0.5

oedema

0

0

0

0

0

0

7251

erythema

1

0

0.5

7245

1

0

0.5

oedema

0

0

0

0

0

0

7252

erythema

0

1

0.5

7246

1

1

1

oedema

0

0

0

0

0

0

D = dead

Highest grade observed: very slight erythema, no oedema

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The results show that the test substance is very slightly irritating to skin. It causes minimal erythema and no oedema. The contact time is too long but the test substance was not moistened so contact with the skin may not have been optimal. Reversibility cannot be assessed but the effects are of such minimal nature that full reversibility is expected well within 14 days. Although this study has 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 not a skin irritant according to GHS.
Executive summary:

The primary irritation of p-TSA 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. Observations 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: very slight erythema after 72 hours: very slight erythema. No difference was observed between intact and abraded skin.

The results show that the test substance is very slightly irritating to skin. It causes minimal erythema (Very slight erythema - barely perceptible)

and no oedema. The contact time is too long but the test substance was not moistened so contact with the skin may not have been optimal. Reversibility cannot be assessed but the effects are of such minimal nature that full reversibility is expected well within 14 days. Although this study has many deviations performing a new study is not warranted because it is not expected to provide any new information. With this study it has been shown that the substance is not a skin irritant according to GHS.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
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: The study was performed according to a method similar to OECD 405 and pre-GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
other: U.S. FDA (Fed. Reg. 28(119), 5582, 1963)
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:
6
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:
mean
Remarks:
all animals
Time point:
other: 14-48-72h mean
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72 h mean
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72h mean
Score:
0.8
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: a score of 1 remained in one animal after 7 days, for the other 5 animals all signs had dissapeared within 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24-48-72h mean
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight corneal damage in one out of six rabbits at 24 hours only, and slight redness of the conjunctivae in all (six) rabbits.

results:

Rabbit No and sex

Region of the eye

Hours after instillation

Average 24-48-72 hours

24

48

72

7(days)

1

Cornea

Degree of opacity

1

0

0

0

0.33

Iris

0

0

0

0

0

Conjunctivae

Redness

1

1

1

1

1

Chemosis

0

0

0

0

0

2

Cornea

Degree of opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

Redness

1

1

0

0

0.66

Chemosis

0

0

0

0

0

3

Cornea

Degree of opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

Redness

1

0

0

0

0.33

Chemosis

0

0

0

0

0

4

Cornea

Degree of opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

Redness

1

1

1

0

1

Chemosis

0

0

0

0

0

5

Cornea

Degree of opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

Redness

1

1

1

0

1

Chemosis

0

0

0

0

0

6

Cornea

Degree of opacity

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctivae

Redness

1

1

1

0

1

Chemosis

0

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The study resulted in very slight corneal damage in one out of six rabbits that was reversible within one day, and slight lesions of the conjunctivae in all (six) rabbits which was not considered a positive reaction. Therefore the test substance is considered not irritant to the eye according to GHS.
Executive summary:

A study was performed to access the eye irritancy of para-toluenesulfonamide. 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 a sthe control. Observations were made after 24, 48, 72 hours and after 7 days. Very slight corneal damage was observed in one out of six rabbits which was completely resolved the next day. Slight erythema of the conjunctivae was observed in all (six) rabbits, but this was not severe enough to be considered a positive reaction. Therefore the test substance is considered not irritant to the eye according to GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

The primary irritation of p-TSA to the skin is measured by an occlusive patch-test technique on the abraded and intact skin of albino rabbits.

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: very slight erythema after 72 hours: very slight erythema. No difference was observed between intact and abraded skin.

The results show that the test substance is very slightly irritating to skin. It causes minimal erythema (Very slight erythema - barely perceptible) and no oedema.

The study was performed according to methods similar to OECD404, but with the following relevant deviations from the current guidelines:

  • exposure period 24 hours: this would result to a comparable worst case condition
  • rabbit skin is exposed under occlusion: worst case condition
  • the test substance is not moistened to ensure optimal skin contact: Due to full occlusion and 24 hour rather than 4 hour exposure, this is likely of no consequence.
  • the animal skin is exposed intact and abraded: Abraded would represent worst case condition.
  • it cannot be assessed if/when effects are reversible. Observations were made up to 72 hour after exposure: The highest grades observed only consisted of very slight erythema. This was at 72 hours still visible in 2/11 animals and can be expected to completely resolve.

Eye irritation

A study was performed to access the eye irritancy of para-toluenesulfonamide. 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, and 72 hours and after 7 days. Very slight corneal damage was observed in one out of six rabbits which was completely resolved the next day. Slight erythema of the conjunctivae was observed in all (six) rabbits, although this reaction was not severe enough to be considered a positive reaction.

Respiratory irritation:

Vp is (less than) 2.86*10-7 kPa (= 0.0003 Pa) at 20°C, and the respirable fraction (≤ 4 µm) of the crystalline solid is 0%. 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 an in combination of the lack of irritation seen in skin and eye irritation studies, respiratory irritation is not likely to occur.


Justification for selection of skin irritation / corrosion endpoint:
Only study available

Justification for selection of eye irritation endpoint:
Only study available

Justification for classification or non-classification

The available data indicate that even following 24 hr dermal exposure under occlusive conditions only slight erythema was visible. The substance therefore does not need to be classified according to GHS.

A study evaluating the irritating effects in rabbirt eyes resulted to limited effects in 1/6 rabbits that was reversible within one day, and slight lesions of the conjunctivae in all (six) rabbits which was not considered a positive reaction. Therefore the test substance is considered not irritant to the eye according to GHS.

There are no data that that would lead to consider respiratory irritation. There is no need to consider classification for STOT-SE Cat.3 regarding respiratory irritation.