Registration Dossier

Administrative data

Description of key information

LD50 oral = 1410 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:
experimental study
Adequacy of study:
key study
Study period:
Aug 25 - Sept 27, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well described GLP compliant study conducted to recognized international test guidelines
Justification for type of information:
Read-across from supporting substance (structural analogue or surrogate)
Qualifier:
according to
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 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:
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 symptoms were irreversible in 1 or 2 animals. Other clinical signs included abnormal gait, ptosis and piloerection in several animals from all doses on day 1 and then reversible within 2 days for males at 2000 mg/kg and females at 1250 mg/kg. For females at 1600 and 2000 mg/kg these symptoms were observed throughout the 28 day observation period.
Body weight:
At the end of 28-days, body weight increased in 2 of 3 males that survived. Increased in 2 of 3 surviving females exposed to 1250 mg/kg, and in 1 of 2 surviving females exposed to 1600 mg/kg. Body weight decreased in single surviving female exposed to 2000 mg/kg. Both increases and decreases at 28 days were at most and least +/- 27% of initial body weights.
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).

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance has an acute oral LD50 of 1410 mg/kg bw. The NOAEL is 1250 mg/kg/bw.
Endpoint conclusion
Dose descriptor:
LD50
1 410 mg/kg bw

Additional information

The key study is a 1988 GLP guideline study of male and female rats exposed by oral gavage to toluene-4-sulphonic acid (CAS No, 104-15-4). 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 support the LD50 value of 1410 mg/kg bw reported in the key study.

There are not data for dermal acute toxicity. The aromatic sulphonic acids are corrosive and therefore with regard to animal welfare, dermal studies are not recommended. There are however acute dermal toxcity studies for the closely related hyrotropes that are the salt form of the sulphonic acids. The LD50 for the salts is >2000 mg/kg bw.

A single acute inhalation study concluded the acids are harmful at saturated air conditions as 3 of 6 animals died. A concentration was not reported.

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 resdults could be taken into account.

The studies with the salts (hydrotropes) provide valid read-across for the acids. The specific cation is not expected to have an appreciable effect on fate, ecotoxicity or mammalian toxicity and therefore the dataset for the entire hydrotropes category can be applied broadly. 

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 contac

No basis for acute toxicity classification is found.