p-toluenesulphonyl isocyanate

Endpoint summary

Description of key information

Acute oral toxicity (males and female rats): LD50 = 2330 mg/kg bw
Acute dermal toxicity (male and female rats): LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A 2 page study report is available. The study was performed pre-GLP. The study was performed according to a method similar to OECD401. No data on substance identity or composition.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Very high dose volume. Animals were only observed for signs of intoxication and necropsy was performed on surviving animals.

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Doses:

8.3, 10.0, 12.0, 14.4, 17.3 ml/kg

No. of animals per sex per dose:

5

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 330 mg/kg bw

95% CL:

2 080 - 2 600

Results:

Within a few hours after dosing the rats showed sluggishness, followed by loss of consciousness. Death occurred between 4 and 50 hours after dosing. Later on the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors at autopsy revealed dark discolouration of the liver in the rats of all dose groups. Some of the rats showed mottled kidneys. No other signs of treatment-related gross alterations were seen.

Dose		Mortality
Suspension ml/kg	Test substance g/kg	males	females	%
8.3	2.08	1/5	3/5	40
10.0	2.50	1/5	4/5	50
12.0	3.00	4/5	5/5	90
14.4	3.60	3/5	5/5	80
17.3	4.33	5/5	5/5	100

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

From the mortality-figures the LD50 of para-toluene sulphonamide was calculated to be 2.33 g per kg body weight, with 2.08 and 2.60 as the 95% confidence limits. Therefore, the test substance does not need to be classified for Acute Oral Toxicity in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Executive summary:

An acute oral toxicity study was performed according to a method similar to OECD401 and pre-GLP. 5 male and 5 female rats were dosed with 8.3, 10.0, 1.20, 14.4 or 17.3 ml/kg bw. The animals were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors. Within a few hours after dosing the rats showed sluggishness, followed by loss of consciousness. Death occurred between 4 and 50 hours after dosing. Later on the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors at autopsy revealed dark discolouration of the liver in the rats of all dose groups. Some of the rats showed mottled kidneys. No other signs of treatment-related gross alterations were seen. From the mortality-figures the LD50 of para-toluene sulphonamide was calculated to be 2.33 g per kg body weight, with 2.08 and 2.60 as the 95% confidence limits. Therefore, the test substance does not need to be classified for Acute Oral Toxicity in accordance with the criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 330 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

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

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

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

Preliminary study:

Not applicable

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

Not relevant

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The results of PTSA are read across to PTSI. This is considered justified because PTSI is extremely reactive with water and reacts instantaneously into the source substance PTSA.This will occur on the skin and also inside the body. Thus, in practice, exposure will be to PTSA and not PTSI. Due to this extreme reactivity it is considered ethically not appropriate to perform the acute toxicity studies with PTSI.

 

An acute oral toxicity study with PTSA was performed according to a method similar to OECD401 and pre-GLP. 5 male and 5 female rats were dosed with 8.3, 10.0, 1.20, 14.4 or 17.3 ml/kg bw. The animals were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors. Sluggishness and loss of conscience were observed. Mortality was observed between 4 and 50 hours after dosing. The LD50 of PTSA was calculated to be 2.33 g per kg body weight, with 2.08 and 2.60 as the 95% confidence limits.

 

An acute dermal toxicity test (limit test) was performed with PTSA as testing material. The test was performed according to OECD guideline 402 (Acute dermal toxicity). 5 male and 5 female rats were dermally exposed to the substance at 2000 mg/kg bw for 24 hours. 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. Overall body weight of all animals increased during study. In conclusion, the acute dermal median lethal dose (LD50) was found to be >2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
One pre-GLP study available which was performed similar to the OECD guideline 401.

Justification for selection of acute toxicity – dermal endpoint
Reliable GLP study according to OECD Guideline 402

Justification for classification or non-classification

The test material does not meet the criteria for classification and will not require labelling for acute toxicity in accordance with the criteria outlined in Annex I of 1272/2008/EC (CLP) and Annex VI of 67/548/EEC (DSD).