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Administrative data

Description of key information

4-nitrotoluene-2-sulphonic acid was testet in a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test by oral administration in rats. The NOAEL was 175 mg/kg bw/ day.
Furthermore, based on data with the structural analogue 3-nitrobenzenesulphonate (CAS 127-68-4) there is sufficient weight of evidence that 4-Nitrotoluene-2-sulphonic acid itself does not have a dangerous property that has not been detected in the available Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening test. Consequently, additional testing concerning sub-chronic toxicity with the registered substance is considered to be of very low priority.
In addition, taking the exposure considerations for this substance into account, and for the sake of animal welfare, further vertebrate studies (i.e. sub-chronic toxicity study in rats (90-day; OECD 408) and pre-natal developmental toxicity study in rats (OECD 414)) are not justified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
175 mg/kg bw/day

Additional information

A Combined Repeat Dose Reproductive/Developmental Toxicity Screening Test according to OECD TG 422 in compliance with GLP is available to assess the repeated dose toxicity of 4-nitrotoluene-2-sulphonic acid (GINC, Japan). In this study, the test substance was administered by gavage to 12 rats per sex and dose of 0, 175, 350 and 700 mg/kg. It was shown that in males and females of the groups of 350 mg/kg or 700 mg/kg respectively, mucosal hyperplasia in the stomach limiting ridge and mucosal atrophy in the cardiac region were seen. Furthermore, in males and females of the 700 mg/kg group, erosion and superficial hemorrhage in the glandular stomach and soft feces with partial black changes were observed. Moreover, males of the 700 mg/kg group exhibited retarded body weight gain, low food consumption, low values for mean corpuscular volume and mean corpuscular hemoglobin, low values for total protein andα1-globulin fraction ratio. In females, of the 700 mg/kg group one animal died and one animal was sacrificed in extremis, and also retarded body weight gain was observed.

Under the conditions of this study the NOAEL was determined to be 175 mg/kg/day.

Data with structural analogue 3-nitrobenzenesulphonate (CAS 127-68-4):

Wernick et al. (1975) reported a chronic toxicity study using dogs with the structural analogue sodium 3-nitrobenzenesulphonate. Male and female Beagle dogs were offered a concentration of 19.5 or 97.5 mg/kg/day via the diet. The study duration was 2 years. There were no note-worthy differences in organ-to-body weight ratios and hematological, blood chemical, or urinalysis parameters between the controls and the 19.5 or 97.5 mg/kg/day dose groups. There were also no test substance-related gross or microscopic changes in tissues or organs. Furthermore, electron microscopy of liver and urinary bladder sections from all dogs that were killed at 18 months did not indicate any ultrastructural changes.

Therefore, there is sufficient weight of evidence that 4-Nitrotoluene-2-sulphonic acid itself does not have a dangerous property that has not been detected in the available combined repeated dose toxicity study with the reproduction/developmental toxicity screening test. Consequently, additional testing concerning sub-chronic toxicity with the registered substance is considered to be of very low priority.

Taking the above mentioned scientific arguments together with the exposure considerations for this substance into account, and for the sake of animal welfare, further vertebrate studies concerning repeated dose toxicity (i.e. sub-chronic toxicity study in rats (90-day; OECD 408) are not justified.

Justification for classification or non-classification

EU classification according to annex VI of the Directive 67/548/EEC:

no classification required

GHS classification (EU GHS, CLP 1272/2008)

no classification required