Toluene-2-sulphonamide

Endpoint summary

Description of key information

o-TSA is of low acute toxicity. Acute oral LD50 is 2920 mg/kgbw and dermal toxicity is even much lower.

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 summary is available. 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:

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:

2 920 mg/kg bw

95% CL:

2 610 - 3 230

Results:

Within a few hours after dosing the rats showed sluggishness, followed by loss-of consciousness. Death occurred between 5 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 and kidneys in the rats of all dose groups. No other treatment-related gross alterations were seen.

Dose		Mortality
Suspension ml/kg	Test substance g/kg	males	females	%
8.3	2.08	0/5	0/5	0
10.0	2.50	0/5	3/5	30
12.0	3.00	4/5	2/5	60
14.4	3.60	5/5	3/5	80
17.3	4.33	4/5	5/5	90

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

From the mortality-figures the LD50 of ortho-toluene sulphonamide was calculated to be 2.92 g per kg body weight, with 2.61 and 3.23 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 8.3, 10.0, 1.20, 14.4 or 17.3 ml/kg bw as a 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, followed by loss-of consciousness. Death occurred between 5 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 and kidneys in the rats of all dose groups. No other treatment-related gross alterations were seen. From the mortality-figures the LD50 of ortho-toluene sulphonamide was calculated to be 2.92 g per kg body weight, with 2.61 and 3.23 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:

2 920 mg/kg bw

Quality of whole database:

Although of low quality, the results are in-line with other available information.

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:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Only a summary of study results. See "Executive summary" for all details.

Conclusions:

LD50 > 7940 mg/kgbw when applied as 50% suspension in corn oil to rabbits.

Executive summary:

ACUTE DERMAL TOXICITY Species New Zealand Albino Rabbits

LD50 > 7,940 Mg/Kg 95% Confidence Limits - Mg/Kg

Exposure 24 hours

CONDITIONS Applied as a 50.0% suspension in corn oil

Signs of Intoxication: Reduced appetite and activity for one to two days.

Survivors( 14 Days): Viscera appeared normal.

Dose mg/kg	Initial bw males	Initial bw females	Mortalities/doses Males	Mortalities/doses Females	Mortalities/doses Combined
2000	2.4	-	0/1	-	0/1
5010	2.4	-	0/1	-	0/1
7940	2.3	2.4	0/1	0/1	0/2

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

7 940 mg/kg bw

Quality of whole database:

Although of low quality, the results are in-line with other available information. Substance is of low acute oral toxicity, not requiring classification. Also no classification is required for skin or eye irritation. Information on absorption indicates that p-TSA is rapidly and completely absorbed by oral route, en only 20% by dermal route. Further acute testing by dermal route is therefore scientifically unjustified.

Additional information

Oral:

There are two studies available evaluating the acute oral toxicity:

 

An acute oral toxicity study was performed according to a method similar to OECD 401 and pre-GLP (TNO, 1978). 5 male and 5 female rats were dosed with 8.3, 10.0, 1.20, 14.4 or 17.3 ml/kg bw of a 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, followed by loss-of consciousness. Death occurred between 5 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 and kidneys in the rats of all dose groups. No other treatment-related gross alterations were seen. From the mortality-figures the LD50 of ortho-toluene sulphonamide was calculated to be 2.92 g per kg body weight, with 2.61 and 3.23 as the 95% confidence limits. Therefore, the test substance can be classified in Category V according to GHS.

 

Similar results indicating low acute toxicity following oral dosing in rats were obtained in another study (Younger Labs, 1974). The test substance was dose as a 20.0% suspension in corn oil at dose levels of 2510, 3160, 3980 and 5010 mg/kg. Signs of Intoxication reported were reduced appetite and activity (one to two days in survivors), increasing weakness, collapse, and death. Gross Autopsy of decedents showed haemorrhagic areas of the lungs, liver hyperaemia and gastrointestinal inflammation. In 14-day survivors the viscera appeared normal. The LD50 was determined to be 3570 mg/kg with 95% confidence limits of 3250 and 3930 mg/kg bw.

 

The HPV/SIDS dossier for o-TSA (2002) mentions a more recent study by Japan Ministry of Health and Welfare: 1999. The study was performed according to OECD 401 and in compliance with GLP. SD rats (5 animals/sex/group) were administered o-TSA by gavage at a single dose of 0, 700, 1,000, 1,400 and 2,000 mg/kg bw. Three females given 1,400 mg/kg bw and two females given 2,000 mg/kg bw were found dead but there were no death in males of all treated groups. Sedation, passivity, catalepsy and prostration appeared even at the lowest dose of 700 mg/kg bw. Lateral position, abnormal breathing and hypothermia were also found in both sexes of the higher dosing groups. At autopsy, reddish discoloration of the lung, pale colored areas of the gastric mucosa and cysts in the renal cortex were observed in dead animals. The SIDS evaluation concluded that LD50 values were greater than 2,000 mg/kg b.w. for males and between 1,000 and 2,000 mg/kg b.w. for females. (although less than 50% died at 2000mg/kg bw)

 

All information, including from literature is presented in the table below:

Route	Species (sex and strain)	LD50	Reference(s)
p.o.	Rat (male & female/ Wistar)	LD50 = 2330 mg/kg bw	TNO (1978)
	Rat (male & female; Sprague Dawley	LD50 = 3570 mg/kg	Younger Labs (1974)
	Rat (male & female; Sprague Dawley Crj:CD(SD)	LD50 >2000 mg/kg	(MHW, cited by OECD, 2002) MHW (1999)
	Rat	LD50 ca. 2000mg/kg	Schmähl: 1978 (cited by OECD, 2002)
	Rat	LD50 4870 mg/kg	Marhold et al.: 1986 (RTECS)

 

Dermal:

Data is available from an old study (Younger Labs, 1974). The report is of low validity due to limited reporting, but it indicates that levels of 7940 mg/kg bw of the test substance do not result to mortality when exposed to the skin to two rabbits as a 50% suspension in corn oil.Signs of Intoxication reported were reduced appetite and activity for one to two days. In 14-day survivors the viscera appeared normal. The LD50 was concluded to exceed 7940 mg/kgbw.

 

Further support is available from information on dermal absorption: p-TSA is of low acute oral toxicity, not requiring classification. Also no classification is required for skin or eye irritation. Information on absorption indicates that p-TSA is rapidly and completely absorbed by oral route, but only 20% by dermal route. Further acute testing by dermal route is therefore scientifically unjustified.

 

Inhalation:

vp is0.000066 Pa at 25°C, and the respirable fraction (≤ 4 µm) of the crystalline solid is 0.23%. Additionally, the likelihood of exposures by aerosols from the use of the substance is also low (water solubility is low with 1.6 g/L at 20°C).

Although no data is available via inhalation route, similar low toxicity can be expected.

Justification for selection of acute toxicity – oral endpoint
Key study. Although of low quality, the results are in-line with other available information.

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 (0.000066 Pa at 25°C), and the crystalline solid is of low dustiness (the respirable fraction (≤ 4 µm) is 0.23%). 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 study available

Justification for classification or non-classification

Available information indicates no toxicity by dermal route, and low oral toxicity with an LD50 of 2920 mg/kg resulting to a GHS classification for acute oral toxicity of Cat.5. In the EU however no classification is needed.

By inhalation route no data is available. Testing is however not indicated in view of the low likelihood of exposures. Similar low toxicity can be expected by all routes.

Consequently no classification for acute toxicity is required for EU CLP.

 

The acute oral studies show effects of neurodepression at near lethal doses. Due to low dermal absorption, and unlikely exposures via inhalation (very low vp, solid with no respirable fraction) and general low exposures, no narcotic effects will occur in humans. Classification for STOT-SE Cat.3 for narcotic effects is therefore not indicated.