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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
700 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 reproductive 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.

In the test group of 700 mg/kg to male and female parents, there were no effects of the test substance on the estrous cycle, number of days required until copulation, as well as copulation rates. Additionally, there were neither histological changes in testes and epididymides nor abnormalities in staging of the seminiferous tubules, and there was no testicular toxicity to sperm production and development. In female animals, no abnormalities were found in the gestation period and parturition. There were no effects of the test substance on the numbers of corpora lutea and implantation sites, implantation rate, total number of live newborns, as well as birth and delivery rates. Further, no abnormalities were found in lactation behaviors after parturition. No effects on the fertilities of male and female parental animals were observed up to 700 mg/kg/day the highest dose tested. The NOEL for reproductive toxicity is considered to be 700 mg/kg/day, the highset dose tested, for parental males and females.


Short description of key information:
4-nitrotoluene-2-sulphonic acid was tested in a Combined Repeat Dose Reproductive/Developmental Toxicity Screening Test by oral Administration in rats.
The NOELs for the reproductive/developmental toxicity are considered to be 700 mg/kg/day for parental males and females, and 350 mg/kg/day for pups. The NOAEL for maternal toxicity was determined to be 175 mg/kg/day.

Effects on developmental toxicity

Description of key information
4-nitrotoluene-2-sulphonic acid was testet in a Combined Repeat Dose Reproductive/Developmental Toxicity Screening Test by oral administration in rats. In this study, the NOEL for developmental toxicity was determined to be 350 mg/kg/day, the NOAEL for maternal toxicity was determined to be 175 mg/kg/day.
In addition, no selective prenatal developmental effects have been observed with the structural analogue nitrobenzene (CAS 98-95-6) in rats and rabbits. Hence, 4-Nitrotoluene-2-sulphonic acid which is of much lower bioavailability and half-life time does not present a structural alert either.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
350 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 developmental 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.

In the 700 mg/kg group no external anomalies were observed in pups. There were no effects of the test substance on the sex ratio, number of live pups, number of stillborns and live birth rate. However, in the 700 mg/kg group, there was a tendency towards low body weights in males and females, and towards low viability on day 4 of lactation. These changes were presumed to be secondary effects which arose from toxic changes during the gestation and lactation periods of the mother. The NOAEL for maternal toxicity was determined to be 175 mg/kg/day. The NOEL for developmental toxicity is considered to be 350 mg/kg/day.

Supporting data with structural analogue nitrobenzene (CAS 98-95-6):

The structural analogue nitrobenzene (CAS 98-95-6) showed testicular toxicity and a reduction of male fertility already in the F0 generation in the course of a 2-generation reproductive toxicity study via inhalation at an exposure level of 200 mg/m³ (Dodd et al. (1987)) which is equivalent to 57.6 mg/kg bw if one calculates with a 100% resorption rate and an inhalation rate of 0.8 ml/min/kg in the rat.

In contrast, 4-Nitrotoluene-2-sulphonic acid, did not cause any testicular toxicity or adverse effects on the fertilities of male and female parental animals in the course of a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats via gavage up to 700 mg/kg bw, the highest dose tested. This is an expected observation since the bioavailability of 4-Nitrotoluene-2-sulphonic acid and its half-life time is expected to be much lower (due to the sulphonate group in its structure).

In contrast to the fertility impairing effects, no selective prenatal developmental effects have been observed with the structural analogue nitrobenzene in rats and rabbits (ECB, 2007; EPA, 1987; Tyl, R.W. et al., 1987). Hence, 4-Nitrotoluene-2-sulphonic acid which is of much lower bioavailability and half-life time does not present a structural alert either. Therefore, testing concerning prenatal developmental toxicity/teratogenicity 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 developmental toxicity of 4-nitrotoluene-2-sulphonic acid (i.e. pre-natal developmental toxicity study (OECD 414)) 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