p-toluenesulphonyl isocyanate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From October 2012 to December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study is performed in accordance with GLP and OECD guideline 402.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Toluene-4-sulphonamide

EC Number:

200-741-1

EC Name:

Toluene-4-sulphonamide

Cas Number:

70-55-3

Molecular formula:

C7H9NO2S

IUPAC Name:

4-methylbenzenesulfonamide

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): p-Toluenesulphonamide (PTSA)
- Substance type: White crystalline
- Physical state: Solid
- Lot/batch No.: Confidential
- Expiration date of the lot/batch: Confidential
- Storage condition of test material: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200 g
- Fasting period before study:
- Housing: animals were housed in suspended solid floor polypropene cages furnished with woodflakes. Animals were housed individually during the 24-hour exposure period and in groups of 4, by sex, for the remainder of the study
- Diet (e.g. ad libitum): ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 07 November 2012 To: 28 November 2012

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Distilled water and dimethyl sulphoxide (DMSO)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed by wiping the treated skin and surrounding hair with cotton wool moistened with distilled water and dimethyl sulphoxide (DMSO)
- Time after start of exposure: 24 hours after application of test substance

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight
- Concentration (if solution): no information available
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): no information available
- Concentration (if solution): no information available
- Lot/batch no. (if required): no information available
- Purity: no information available

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual bodyweights prior to dosing and 7 and 14 days after treatment. Mortality and clinical observations at 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

not relevant

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 0/10 deaths

Mortality:

No mortality was observed

Clinical signs:

other: No signs of systemic toxicity were observed

Gross pathology:

One male showed thickened non-glandular epithelium of the stomach at necropsy. No abnormalities were noted at necropsy of the other animals.

Other findings:

There were no signs of dermal irritation

Any other information on results incl. tables

Not relevant

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this test, the acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater then 2000 mg/kg bw. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with according to the criteria outlined in Annex I of 1272/2008/EC (CLP) and Annex VI of 67/548/EEC (DSD).

Executive summary:

An acute dermal toxicity test (limit test) was performed with p-Toluenesulphonamide as testing material. The test was performed according to OECD guideline 402 (Acute dermal toxicity) in a group of 10 rats (5 males, 5 females). The rats were dermally exposed to the substance at 2000 mg/kg bw for 24 hours. The substance was applied to a shorn skin (approximately 10% of body surface). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

No mortality was observed in the 14 days period after exposure. No signs of systemic toxicity were observed during clinical observation. No signs of dermal irritation were noted in the animals. One male showed thickened non-glandular epithelium of the stomach at necropsy. No abnormalities were noted at necropsy of the other animals. Overall body weight of all animals increased during study.

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat, was found to be >2000 mg/kg bw. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with the criteria outlined in Annex I of 1272/2008/EC (CLP) and Annex VI of 67/548/EEC (DSD).