Registration Dossier

Administrative data

Description of key information

Tosyl chloride is of low acute toxicity. Acute oral LD50 was established at 4680 mg/kgbw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A 2 page study study report. The study was performed pre-GLP. The study was performed according to a method similar to OECD401.
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:
3.00, 3.60, 4.33, 5.18, 6.20 g/kg
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 680 mg/kg bw
95% CL:
4 280 - 5 130

Results:

Within a few hours after dosing the rats showed sluggishness. Later on unconsciousness was frequently observed, especially in the two highest dose groups. Death occurred between 3 hours and 3 days after dosing. Thereafter the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors revealed no treatment-related gross alterations.

Dose

Mortality

Suspension ml/kg

Test substance g/kg

males

females

%

12.0

3.00

0/5

0/5

0

14.4

3.60

1/5

0/5

10

17.3

4.33

2/5

1/5

30

20.7

5.18

3/5

4/5

70

24.8

6.20

5/5

5/5

100

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The LD50 of para-toluene sulphochloride was calculated to be 4.68 g per kg body weight with 4.28 and 5.13 as the 95 % confidence limits.
Therefore, the test substance can be classified in Category V according to GHS.
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 3.00, 3.60, 4.33, 5.18 or 6.20 g/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. Later on unconsciousness was frequently observed, especially in the two highest dose groups. Death occurred between 3 hours and 3 days after dosing. Thereafter the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors revealed no treatment-related gross alterations.The LD50 of para-toluene sulphochloride was calculated to be 4.68 g per kg body weight with 4.28 and 5.13 as the 95 % confidence limits. Therefore, the test substance can be classified in Category V according to GHS.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
4 680 mg/kg bw
Quality of whole database:
The results are in-line with other available information.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Low quality data. In view of irritation properties to skin and indicated low systemic toxicity via oral route there is no need to perform an additional acute toxicity study by dermal route.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Indirect reference: Report of study to EPA as referenced in OECD SIDS dossier on 4-methylbenzenesulfonyl chloride; very limited reporting; no guideline study applying only one animal at three dose levels each.
Test type:
other: No data
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
no data
Vehicle:
corn oil
Details on dermal exposure:
no data
Duration of exposure:
24 hours
Doses:
3,160, 5,010 and 7,940 mg/kg
No. of animals per sex per dose:
1
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 010 mg/kg bw
Based on:
test mat.
Mortality:
The animals dosed at 3160 mg/kg (1 male) and 5010 mg/kg (1 female) both survived.
One male animal that was dosed at 7940 mg/kg, died within 9 days.
Clinical signs:
Sign of intoxication: reduced appetite and activity (2 - 3 days in survivors). Increased weakness, collapse, death
Gross pathology:
Necropsy: lung hyperomia, liver & kidney discolouration, enlarged gall bladder, gastrointestinal inflammation

Mortality:

Animal No.

Dose

Weight (Ave)

Mortality

Time of mortality

M

F

M

F

Combined

1

3,160

220

 -

 0/1 

 -

 0/1 

9 days

2

5,010

 -

180

 -

 0/1 

 0/1 

3

7,940

210

 -

 1/1 

 -

 1/1 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
LD50 > 5010 mg/kg.
Executive summary:

Tosyl chloride was applied as a 40% solution-suspension in corn oil on the skin of New Zealand Albino Rabbits for 24 hours. The levels were 3160, 5010 and 7940 mg/kg bw , that were applied to respectively one male, one female and one male animal.

There were some signs of intoxication, consisting of reduced appetite and activity for 2 - 3 days in two survivors that were treated with 3160 and 5010 mg/kg bw. The animal treated with 7940 mg/kg bw showed increased weakness, collapse, and death after 9 days. At necropsy, lung hyperaemia, liver & kidney discolouration, enlarged gall bladder, and gastrointestinal inflammation were observed. The LD50 was concluded to be greater than 5,010 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 010 mg/kg bw
Quality of whole database:
Low quality data. In view of irritation properties to skin and indicated low systemic toxicity via oral route there is no need to perform an additional acute toxicity study by dermal route.

Additional information

Oral:

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 3.00, 3.60, 4.33, 5.18 or 6.20 g/kg bw administered as 25 % (w/v) suspension in propylene glycol. 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. Later on unconsciousness was frequently observed, especially in the two highest dose groups. Death occurred between 3 hours and 3 days after dosing. Thereafter the survivors recovered gradually and looked quite healthy again at the end of the observation period. Macroscopic examination of the survivors revealed no treatment-related gross alterations. The LD50 of para-toluene sulphochloride was calculated to be 4.68 g per kg body weight with 4.28 and 5.13 as the 95 % confidence limits. Therefore, the test substance can be classified in Category V according to GHS.

 

A more recent study was performed in support of the OECD HPV evaluation, confirming the relative low toxicity by oral route. The study was performed according to the OECD 423 ‘Acute toxic class’ method and in compliance to GLP.

Test substance was administered as solution in corn oil at levels of 2,000, 2,000 and 5,000 mg/kg respectively, to 3 female rats for each test by gavage. The volumes administered were 10 ml/kg at 2000 mg/kg dose level and at 20 ml/kg at 5000 mg/kg dose. Test animals were observed for 14 days after the administration. The observation included clinical signs, mortality, body weight, necropsy, and histopathology. No dead animals were observed at all doses.

Clinical signs showed mucous diarrhea occurring from 0.5 hours after the administration with contamination of the perineal region including the anal region and abdominal region for all animals, and was resolved the next day. Depilation at the perineal region was observed on day 9 and 11 for two animals treated 2000 mg/kg. Depilation of the anal and perineal region including, haematological scab around the anal region were observed from day 9 in 2 animals treated 5000 mg/kg which had not recovered by day 14. Body weights of some animals were decreased but were recovered and increased during the test period. At necropsy, all animals displayed thickening of cutaneous membrane in the nonglandular stomach. Histopathological findings included several cases of ulceration and mild to severe inflammation with hyperkeratosis of nongranular stomach in all the test groups and mild thickening of epithelial layer in all treated animals.

The study concluded to an LD50 above 5000 mg/kgbw.

 

Dermal:

The OECD SIDS evaluation on Tosyl chloride references a report of an acute dermal toxicity study in rabbits. In this study Tosyl chloride was applied as a 40% solution-suspension in corn oil on the skin of one New Zealand Albino Rabbits for 24 hours at a level of 3160, 5010 and 7940 mg/kg bw each.

There were some signs of intoxication, consisting of reduced appetite and activity for 2 - 3 days in the two survivors that were treated with 3160 and 5010 mg/kg bw. The animal treated with 7940 mg/kg bw showed increased weakness, collapse, and dead within 9 days. At necropsy, lung hyperaemia, liver & kidney discolouration, enlarged gall bladder, and gastrointestinal inflammation were observed. The LD50 was concluded to be greater than 5,010 mg/kg.

 

This study indicating low toxicity via dermal route is of low validity in view of limited reporting and insufficient design, and data are based on indirect referencing from OECD SIDS evaluation of Tosyl chloride. The study although has been assigned 'Reliable with restrictions' following OECD SIDS evaluation with peer review.

In view of irritation properties to skin and low systemic toxicity as indicated by the acute oral LD50 of 4680 mg/kg, there is no need to perform an additional acute toxicity study by dermal route.

 

Inhalation:

Exposures by inhalation are unlikely in view of the low vp of 0.13 Pa at 20°C, its low dustiness (the respirable fraction (≤ 4 µm) of the crystalline solid is below 0,04%; besides the substance is hygroscopic) and low likelihood of exposures by aerosols with uses limited to chemical intermediate in industrial settings. Furthermore Tosyl chloride readily hydrolyses to toluene sulfonic acid and HCL which are both strong acids. In combination with the very low systemic toxicity as indicated by the acute oral LD50 of 4680 mg/kg, inhalation of dust particles will therefore lead to respiratory irritation rather than expected to results in systemic toxicity.

Justification for selection of acute toxicity – oral endpoint

Available proprietary study reportig highest level of toxicity

Justification for selection of acute toxicity – inhalation endpoint

In accordance with column 2 of REACH Annex VIII, the test for acute inhalation toxicity (required in section 8.5) does not need to be conducted. Vp is low ( less than 2.86*10-7 kPa (= 0.0003 Pa) @ 20°C), and the crystalline solid is of low dustiness (the respirable fraction (≤ 4 µm) is 0%) and hygroscopic. In combination of low likelihood of exposures by aerosols from the use of the substance and the general low acute toxicity, testing of acute toxicity by inhalation is not necessary.

Justification for selection of acute toxicity – dermal endpoint

Only data available.

Justification for classification or non-classification

Tosyl chloride is of low acute toxicity. There are two reasonably high validity studies available resulting to a LD50 of 4680 mg/kg bw and LD50 > 5000 mg/kg bw. Classification for GHS could be Cat. 5 or even not classified. For EU implementation of GHS no classification is required.

Available data also indicate low acute toxicity via dermal route with LD50 > 5010 mg/kg bw. Although of low validity data is consistent with other available data indicating low systemic toxicity and now classification is indicated.

Data via inhalation route are lacking, but in view of low likelihood of exposures and low systemic toxicity there is no reason for classification or further studies.