Toluene-4-sulphonic acid

Endpoint summary

Description of key information

The ASA Category comprises the following 5 aromatic sulphonic acids:

TSA, Toluene-4-sulphonic acid (EC 203-180-0, CAS 104-15-4)

XSA, (Xylenes and 4-ethylbenzene) sulphonic acid (EC 701-247-3, CAS -) Former EC 246-839-8

CSA, p-cumene sulphonic acid (EC 240-210-1, CAS 16066-35-6)

BSA, Benzene sulphonic acid (EC 202-638-7, CAS 98-11-3)

HBSA, 4-hydroxybenzensulphonic acid (EC No. 202-691-6, CAS No. 98-67-9)

The acute oral toxicity was assessed with available studies on ASA and related salt (Hydrotropes category). Hydrotropes could be used in read across for the related acid form.

The key study is a 1988 GLP guideline study of male and female rats exposed by oral gavage to toluene-4-sulphonic acid. The LD50 value was 1410 mg/kg bw. Given the predominance of deaths occurring within the day of exposure and the necropsy findings, it is likely that the deaths were a result of the acidity / corrosivity of the test substance. The internal examination findings (e.g., GI tract filled with blood; stomach haemorrhages and abdomen filled with fluid) suggest a secondary effect (i.e., corrosion) rather than a chemical toxicity.
In addition to the key study, there are 2 supporting acute oral studies a 1977 test of xylenesulphonic acid (CAS No. 25321-41-9) and a 1962 published study of benzenesulphonic acid (CAS No. 98-11-3). Both of these studies, as well as two additional published studies showed comparable LD50 to the one reported in the key study.
The available acute oral toxicity studies do not show any concern confirming the results seen in the test conducted on ASA substance.

There are not data for dermal acute toxicity. The aromatic sulphonic acids are corrosive for skin and therefore with regard to animal welfare, dermal studies are not recommended.
Acute dermal toxicity data is available for two Hydrotropes subgroups, xylene and cumene sulphonates which could be used as supporting information about the absence of dermal toxicity. The values (LD50, rabbit) are greater than 2000 mg/kg bw for all tests, indicating an absence of dermal toxicity within the Hydrotropes category.

There is only one publication for acute inhalation toxicity for BSA which will be used for all the other category members. During the test, 3 of 6 animals died within 14 days after an 8 hour exposure. No deaths were reported for shorter duration exposures (15, 30, 45 minutes; and 1, 2 and 4 hours). There is an acute inhalation toxicity test on Ammonium (xylenes and 4-ethylbenzene) sulfonates performed following official method OECD 403, Acute Inhalation Toxicity. One animal displayed a pronounced case of soft stool on Day 6 an returned to normal in two days. No gross signs of test compound induced adverse effects were observed in the remaining nine animals, there was no mortality and half of the exposed animals showed only slight to moderate congestion of the lungs. Slight weight gains in two animals at 7 and 14 days. The body weights for the remaining 8 animals showed gains within  limits of expectation. Five animals showed slight mottling or slight to moderate congestion of the lungs. The remaining animals did not showed remarkable effects.

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:

Aug 25 - Sept 27, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG colony
- Age at study initiation: males - 7 weeks, females - 8 weeks
- Weight at study initiation: males - 194-202 g; females 181-196 g
- Fasting period before study: overnight
- Housing: in groups of 5
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: August 25 To: September 27, 1988

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

1250, 1600 and 2000 mg/kg for females; 2000 mg/kg for males

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: observations daily starting on day of exposure; body weight weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

Probit analysis

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 410 mg/kg bw

Based on:

act. ingr.

Mortality:

2 of 5 males at 2000 mg/kg; 2 of 5, 3 of 5, and 4 of 5 females died at 1250, 1600 and 2000 mg/kg, respectively. Death almost always occurred within one day of dosing.

Clinical signs:

other: Main clinical signs were hypoactivity, hunched posture, irregular breathing in all animals at all doses on day 1 and then reversible within 3 days for males at 2000 mg/kg and within 2 days for females at 1250 mg/kg. For females at 1600 and 2000 mg/kg the

Gross pathology:

Red discolouration of the GI tract filled with blood; white discouloration of the mucosa of the stomach and intestine; pale adrenals, stomach haemorrhages and abdomen filled with flied (in animals that died spontaneously). No sex specific differences.

Other findings:

NOAEL = 1250 mg/kg bw

Mortality: number of deaths at each dose: 2/5, 3/5 and 4/5 at 1250, 1600 and 2000 mg/kg for females, and 2/5 at 2000 mg/kg for males.

Time of death was Day 1 for all but one animal at 1600 mg/kg that died on day 13.

Clinical signs: hypoactivity, hunched posture, irregular breathing were observed in all animals from all dose groups on day 1 and was reversible within 3 days for males at 2000 mg/kg. For females, the above symptoms plus abnormal gait, ptosis and piloerection were seen in all animals at 1600 and 2000 mg/kg and were not reversible.

Necropsy findings: Red discolouration of the GI tract filled with blood, white discolouration of the mucosa of the stomach and intestine, pale adrenals, growing together of the stomach and nearby organs, stomach haemorrhages and abdomen filled with fluid (in animals that died).

Conclusions:

LD50 = 1410 mg/kg bw based on active ingredient
NOAEL = 1250 mg/kg/bw based on active ingredient

Executive summary:

The acute Oral Toxicity of Toluene 4-sulphonic acid was assessed following official method OECD 401, Acute Oral Toxicity. The test was performed with three concentrations (1250, 1600 and 2000 mg a.i./kg for females rats; 2000 mg a.i./kg for males rats) administered by oral gavage. 2 of 5 males at 2000 mg/kg; 2 of 5, 3 of 5, and 4 of 5 females died at 1250, 1600 and 2000 mg/kg, respectively. Death almost always occurred within one day of dosing. Given the predominance of deaths occurring within the day of exposure and the necropsy findings, it is likely that the deaths were a result of the acidity / corrosivity of the test substance. The internal examination findings suggest a secondary effect (i.e., corrosion) rather than a chemical toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 410 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: Read across from analogue substance

Adequacy of study:

key study

Study period:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not a guideline study; some details on methodology, but concentration of test substance that the animals were exposed to is not reported. Indicated only as "saturated air".

Principles of method if other than guideline:

Exposure to concentrated vapour is continued for time periods in a logarithmic series with a ratio of the two extending from 15 minutes to 8 hours until the inhalation period killing about half the number of rats within 14 days of observation is defined.

GLP compliance:

no

Test type:

fixed concentration procedure

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

For exposures of 2, 5 or 10 minutes, a static technique was used by saturating the air with 50-100 g of test substance for 24 hours in a closed chamber. For exposures beyond 10 minutes a flowstream of saturated vapour was used.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

>= 0.25 - <= 8 h

Concentrations:

Not reported. Air was saturated with 50-100 g of test substance

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not reported
- Necropsy of survivors performed: no
- Other examinations performed: none reported

Sex:

not specified

Dose descriptor:

LC50

Effect level:

>= 50 - ca. 100 other: mg

Based on:

test mat.

Exp. duration:

8 h

Mortality:

3 of 6 animals died within 14 days after an 8 hour exposure. No deaths were reported for shorter duration exposures (i.e, 15, 30, 45 minutes; and 1, 2 and 4 hours).

Conclusions:

LC50 = 50 g

Executive summary:

The acute inhalation toxicity of Benzene sulphonic acid was assessed with a test where only few details are available. Based on the results, 3 of 6 animals died within the 14-day observation period following an 8 hour exposure to a saturated air vapour of test substance. Concentration of test substance that the animals were exposed to is not reported, only indication as "saturated air".

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Since it is not possible to directly assess the toxicity of sulphonic acids due to the corrosion/irritation effects, read-across from the hydrotopes results could be taken into account.

The internal examination findings on aromatic sulphonic acid suggested a secondary effect (i.e., corrosion) rather than a chemical toxicity. This consideration is supported by the data available on hydrotropes. The acute oral toxicity has been tested at least for each member of the hydrotropes subgroup (toluene, xylene and cumene). The results (rat LC50) ranging from 3000 to 16000 mg/Kg bw, depending on the tested dose. No deaths occurred up to the highest tested doses for each available test. The results indicate that hydrotropes are not toxic for acute oral exposure. The aromatic sulphonic acids are almost completely ionized in watery environments even at low pH. The salts of these acids are the hydrotropes (or “sulphonates”) which include ammonium, calcium, potassium and sodium cations. In principle the salts get dissociated when in contact with water, so forming back to the acids. Because of their close chemical similarities and because much of the production of the aromatic sulphonic acids goes to manufacturing the salts, the extensive dataset for the hydrotropes can also be used as a source of read-across for endpoints in an aromatic sulphonic acid dossier. This is particularly relevant for studies that are conducted in water (e.g., ecotoxicity and biodegradation) as well as for mammalian toxicity studies where the relatively high acidity of the acid form has an immediate and harsh local effect, whereas the salt form provides an indication of potential systemic toxicity beyond the site of application or initial contact.

 

No basis for acute toxicity classification is found.