Registration Dossier

Administrative data

Description of key information

A GLP guideline study with p-toluenesulphonic acid (CAS No. 104-15-4) reported no adverse effects to male and female rats exposed orally for 28 days. The highest dose was 500 mg/kg bw/day (>490 mg/kg bw/day based on >98% active ingredient). Therefore the NOAEL was set at 500 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline and GLP study but without complete documentation available
Justification for type of information:
Grouping of structurally similar substances (category approach)
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Not available
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
Not available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 days
Frequency of treatment:
one per day, 7 days per week
Remarks:
Doses / Concentrations:
4, 20, 100 and 500 mg/kg bw/d
Basis:
actual ingested
No. of animals per sex per dose:
10 or more
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: In a preliminary study to establish the doses for the definitive study, a single dose of 1250 mg.kg bw of the test substance resulted in 40% mortality of female rats. The definitive study high dose was set at 500 mg/kg bw/d
Positive control:
no
Observations and examinations performed and frequency:
no details available
Sacrifice and pathology:
no details available
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
increased salivation in high dose males
Mortality:
mortality observed, treatment-related
Description (incidence):
increased salivation in high dose males
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
acidic urine in high dose males and females
Dose descriptor:
NOAEL
Effect level:
>= 500 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Critical effects observed:
not specified
Conclusions:
NOAEL in the definitive study is 500 mg/kg bw/day.
A preliminary dose-finding study indicated mortality of females at 1250 mg/kg bw
Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
chronic
Species:
rat

Additional information

The NOAEL in the definitive 28 -day oral study of toluene-4-sulphonic acid is 500 mg/kg bw/day. A preliminary dose-finding study indicated mortality of females at 1250 mg/kg bw. And while this is a valid study there were no adverse effects observed at the highest dose tested. Therefore a read-across is included to view a derived NOAEL for a related substance. Hydrotropes are the salt form of the sulphonic acids.

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

There are a total of 6 oral repeated dose studies for the hydrotrope sodium xylene sulphonate (CAS No. 1300-72-7). The key study is a 90-day oral study, conducted in 1968, is generally comparable to the OECD 408 guideline study. In that study, the highest dose for female rats - 4092 mg active ingredient (a.i.) per kilogram body weight - resulted in a loss in relative weight of the spleen. The 2nd highest dose for females - 763 mg a.i. per kilogram body weight - had no measureable adverse effects and therefore establishes the repeat dose oral NOAEL for the test substance. The highest oral dose for male rats - 3534 mg a.i. per kilogram body weight - had no measurable adverse effects. No adverse effects were reported in a 90 day mouse study with the same substance.

Justification for classification or non-classification

Classification for STOT is relevant where significant toxic effects are seen from single or repeated dose studies. No such significant toxicity is seen in all available studies

No classification for STOT is warrented at present under 67/548/EEC or Regulation 1272/2008.