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Description of key information

Justification for selection of carcinogenicity via oral route endpoint:
One publication available.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: feed
Duration of treatment / exposure:
24 months
Frequency of treatment:
Test animals received weekly doses, based on their body weight and food consumption.
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
0.4 mg/kg bw/day (nominal)
Dose / conc.:
2 mg/kg bw/day (nominal)
Dose / conc.:
10 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
No. of animals per sex per dose:
75 rats per sex
Control animals:
yes
Details on study design:
The doses were selected based on the results of 13-week oral (diet) toxicity studies in Fischer 344 rats.
Sacrifice and pathology:
Ten rats per sex per dosegroup were sacrificed following six and 12 months, with surviving animals sacrificed at the end of the 24-month treatment.
Details on results:
Survival rates and mean survival duration did not differ among control and treated groups in either sex. Dose-related reductions in body weight (5- 14% reduction in animals given 10 mg TNT/kg/day, and 30-33% decreases in the 50 mg/kg/day groups) and food intake were observed in both males and females. There was a dose-related increase in the incidence of hepatocellular hyperplasia in male rats (23/54, p<0.01;34/55,p<0.01) in the10 mg/kg/day and 50 mg/kg/day dose groups, respectively.Hyperplasia was elevated in the kidney(10 mg/kg/day: 7/47,p<0.05) and urinary bladder (10 mg/kg/day: 12/47,p<0.01) in female rats at doses of 10 mg/kg/day or greater.The incidences of benign and malignant urinary bladder tumors were significantly increased in treated female rats in the 50 mg/kg/day dose group, with an incidence of urinary bladder papilloma and carcinoma (combined) of 17/55 (p<0.01) as compared to 0/54 in controls.
Key result
Dose descriptor:
LOAEL
Effect level:
10 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: clinical signs; body weight; food consumption; ophthalmoscopic examination; haematology; clinical chemistry; organ weights, and gross and tissue morphology.
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

The observance of carcinoma of the urinary bladder suggests that TNT is a carcinogen to F344 rats under the conditions of the present study. Hepatocellular, renal and urinary bladder hyperplasia supports this concept. These hyperplastic/neoplastic lesions were seen at dosed of 10 mg/kg/day or greater. Additional toxic effects of TNT seen primarly at 50 mg/kg/day included increased numbers of circulating platelets, elevated blood calcium, and increased hearth weights. Tissues morphology studies did not support these observations.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
10 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Klimisch rating 1.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The observance of carcinoma of the urinary bladder suggests that TNT is a carcinogen to F344 rats under the conditions of the present study. Hepatocellular, renal and urinary bladder hyperplasia supports this concept. These hyperplastic/neoplastic lesions were seen at dosed of 10 mg/kg/day or greater. Additional toxic effects of TNT seen primarly at 50 mg/kg/day included increased numbers of circulating platelets, elevated blood calcium, and increased hearth weights. Tissues morphology studies did not support these observations.

Based on available data, the pure TNT (concentration of impurities 2,4 -DNT; 2,6 -DNT and 3,4 -DNT in amount of total <0.1) does not meet the criteria for classification as carcinogenic

As far as TNT can contain 2,4 -DNT; 2,6 -DNT and 3,4 -DNT in amount of total >0.1 which are all classified as carcinogenic category 1B according to Regulation EC no 1272/2008, we can expect that TNT with those impurities is carcinogenic (calculation method).

Additional information