2-nitrotoluene

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

other: EU Risk Assessment

Adequacy of study:

other information

Reliability:

other: EU Risk Assessment

Rationale for reliability incl. deficiencies:

other: no reliability is given as this is a summary entry for the EU RAR

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

European Union Risk Assessment Report - 2-Nitrotoluene

Author:

European Commission - European Chemicals Bureau

Year:

2008

Bibliographic source:

Office for Official Publications of the European Communities

Reference 2

Reference Type:

publication

Title:

Etude analytique, toxicologique et biochimique des dérivés mononitrés du toluene

Author:

Ciss M

Year:

1978

Bibliographic source:

Dissertation, Université René Descartes de Paris, Serie E

Reference 3

Reference Type:

publication

Title:

Etude toxicologique des nitrotoluènes: Toxicité à long terme

Author:

Ciss M, Huyen N, Dutertre H, Phu-Lich N and Truhaut R

Year:

1980

Bibliographic source:

Dakar Med 25(4): 293-302

Reference 4

Reference Type:

publication

Title:

SIDS dossier on the OECD HPV chemical 2-nitrotoluene

Author:

KemI

Year:

1994

Bibliographic source:

KemI

Materials and methods

Principles of method if other than guideline:

EU Risk Assessment

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-nitrotoluene

EC Number:

201-853-3

EC Name:

2-nitrotoluene

Cas Number:

88-72-2

Molecular formula:

C7H7NO2

IUPAC Name:

1-methyl-2-nitrobenzene

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

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 21 post partum. Food consumption was lower from 150 mg/kg/d Days 1 to 13 post partum. The parent animals showed increases in liver weight, from 50 mg/kg/d (females) and 150 mg/kg/d (male), and in both kidney and spleen weights (from 150 mg/kg/d in both sexes). In relation to the reproductive system, there was a dosage-related decrease of epididymis, seminal vesicles and prostate weights from 150 mg/kg/d and of testes at 450 mg/kg/d. 3 out of 12 females from the 450 mg/kg/d group died in the immediate post natal period (Day 1 or 2 post-partum), and had dead implantations in the uteri. A dosage-related retardation in pup growth was apparent in all treated groups from the 4thor 8thday post-partum. The mortality of 3 among 12 dams treated with 450 mg/kg/d of 2-nitrotoluene is attributed to systemic toxicity of the test material; consequently, the foetus mortality is seen as a secondary effect of maternal toxicity. The retardation in pup growth could be indicative of developmental toxicity; however, in the absence of further details on its severity we are not sure if this effect could be used for classification or it is only a minor developmental change. In addition, if the retardation in pup growth was considered a toxic effect, it cannot be ruled out that some toxicity was due to the transfer of the substance through the milk.