2-nitrotoluene

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

EU RISK ASSESSMENT 2008

 

The only information available on fertility is from non-standard studies in experimental animals. In rats, 2-nitrotoluene administered in feed at 5000 ppm for 13 weeks causes damage to the testes and the epididymis with a simultaneous reduction in the sperm count and the motility of the sperm in males, and a prolongation of the menstrual cycle among the females. Reduced sperm motility was also observed at 10000 ppm (the highest dose level tested) for the mouse. The testicular effects indicate a need for fertility classification but because they occur at toxic dose levels, while clear-cut effects on fertility seem absent, indeed only toxic for reproduction category 3 under DSD (Xn, R 62) is justified according to EU criteria

Short description of key information:
EU RISK ASSESSMENT (2008)
Studies in animals

Oral

Rats
Within the framework of a study on subchronic and reproductive toxicity, Wistar rats (10 animals/sex/group weighing about 200 g) were administered 0 and 200 mg/kg b.w. of 2- nitrotoluene (99% pure) in olive oil by gavage 5 days/week for 3 months, after an acclimation period of 1 week. Then, 5 treated males were in each case mated with 5 untreated or treated females and 5 untreated males were in each case mated with 5 untreated or treated females.
Treated females were dosed throughout pregnancy but undosed during the lactation period of the offspring; in addition, 2 untreated females, which have been mated with untreated males, were dosed during the lactation period of the offspring. Pups, non-treated, were sacrificed 3month post-partum (Ciss, 1978; Ciss et al. 1980b). There was not treatment related histopathology on either testes or ovaries of parents. In addition, the number of pups from treated and untreated animals was the same. Therefore, it can be said that at the dose used in this study, 2-nitrotoluene did not have any influence on the fertility.
Within the framework of a reproduction/developmental toxicity screening study performed by Huntingdon, 1994 (cited in KemI 1994), male and female CD rats received 2-nitrotoluene at daily doses of 0, 50, 150 or 450 mg/kg/d by gavage in corn oil over a total period of approximately 10 weeks (2 weeks prior to mating, 2 weeks¿ mating period, 20 days¿ pregnancy and 21 days post-partum). Pups were sacrificed on day 21 post-partum. For the 450 mg/kg/d group wet coats generally occurred for both sexes and brown stained coats were also observed in all males followed by most females. Lower body weight gain and food consumption occurred for males from 150 mg/kg/d. For females lower body weight gain occurred during pregnancy for the 450 mg/kg/d group but recovered Day 21 post partum.
Food consumption was lower from 150 mg/kg/d Days 1 to 13 post partum. The parent animal...

Effects on developmental toxicity

Description of key information

EU Risk Assessment (2008)
Oral 
- Rats
Within the framework of a study on subchronic and reproductive toxicity, Wistar rats (10 animals/sex/group weighing about 200 g) were administered 0 and 200 mg/kg b.w. of 2- nitrotoluene (99% pure) in olive oil by gavage 5 days/week for 3 months, after an acclimation period of 1 week. Then, 5 treated males were in each case mated with 5 untreated or treated females and 5 untreated males were in each case mated with 5 untreated or treated females.
Treated females were dosed throughout pregnancy but undosed during the lactation period of the offspring; in addition, 2 untreated females, which have been mated with untreated males, were dosed during the lactation period of the offspring. Pups, non-treated, were sacrificed 3 month post-partum (Ciss, 1978; Cisset al.1980b). Mortality, vitality and behaviour of pups from treated and untreated animals were the same. In addition, no histopathological changes in organs occurred among the young animals regardeless on treatment. Therefore, it can be said that at the dose used in this study, 2-nitrotoluene did not induce developmental toxicity.
Furthermore, there was no toxicity derived from transfer of the substance through the milk.
Within the framework of a reproduction/developmental toxicity screening study performed by Huntingdon, 1994 (cited in KemI 1994), male and female CD rats received 2-nitrotoluene at daily doses of 0, 50, 150 or 450 mg/kg/d by gavage in corn oil over a total period of approximately 10 weeks (2 weeks prior to mating, 2 weeks´ mating period, 20 days´pregnancy and 21 days post-partum). Pups were sacrificed on day 21 post-partum. For the 450 mg/kg/d group wet coats generally occurred for both sexes and brown stained coats were also observed in all males followed by most females. Lower body weight gain and food consumption occurred for males from 150 mg/kg/d. For females lower body weight gain occurred during pregnancy for the 450 mg/kg/d group but recovered Day 2.

Additional information

EU RISK ASSESSMENT 2008

The only information available on developmental toxicity is derived from two non-standard reproduction studies in experimental animals. In one of them carried out in CD rats, the only effect considered as indicative of developmental toxicity was the retardation in pup growth; however, because of the absence of further details on its severity we are not sure if this effect could be used for classification; in addition, if this effect was considered as toxic, it cannot be ruled out that some toxicity was due to the transfer of the substance through the milk. In the other study carried out in Wistar rats, mortality, vitality and behaviour of pups from both treated and untreated animals were the same and no histopathological changes in organs occurred among the young animals regardeless on treatment; therefore, 2-nitrotoluene did not induce developmental toxicity; furthermore, there was no toxicity derived from transfer of the substance through the milk. Differences on results between studies could be due to differences on sensitivity between strains. The classification for developmental toxicity based on available data and the EU criteria is not justified. However, assuming the worst case, it is necessary a risk characterization for developmental toxicity using the LOAEL of 50 mg/kg.

Justification for classification or non-classification

Harmonised classification:

The substance is classified in Category 2 (H361f ) according to the Regulation (EC) No. 1272/2008 (CLP).