2,4,6-trinitrotoluene

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Reference 2

Reference Type:

publication

Title:

Subchronic toxicity of trinitrotoluene in Fischer 344 rats

Author:

B.S. Levine, E.M. Furedi, D.E. Gordon, P.M. Lish, J.J. Barkley

Year:

1984

Bibliographic source:

This article was published in Toxicology, Vol. 32, pp. 253-265, Copyright Elsevier Scientific Publishers Ireland Ltd. (1984)

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,4,6-trinitrotoluene

EC Number:

204-289-6

EC Name:

2,4,6-trinitrotoluene

Cas Number:

118-96-7

Molecular formula:

C7H5N3O6

IUPAC Name:

2-methyl-1,3,5-trinitrobenzene

Details on test material:

Trinitrotoluene, 99.1 +/- 0.4% purity as determined by HPLC

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: dietary admixture

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

TNT was administered as a dietary admixture, and the appropriate test diets were available ad libitum except during 17-19h fast prior to either blood collection in Test Week 13 or routine kill in Test Week 14.

Doses / concentrations

Remarks:

Doses / Concentrations:
1, 5, 25, 125 or 300 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

Ten rats per sex received either 1, 5, 25, 125 or 300 mg/kg/day for 13 weeks. Thirty rats of each sex were included as untreated controls.

Control animals:

yes, concurrent no treatment

Results and discussion

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 1 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

body weight and weight gain

food consumption and compound intake

gross pathology

haematology

2

Dose descriptor:

NOAEL

Effect level:

ca. 5 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

gross pathology

haematology

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Toxic effects following 125 mg/kg/day or greater included decrease food intake and body weight gain, elevated serum cholesterol levels, and anemia (reduced hemoglobin, hematocrit and RBC counts). Splenomegaly, hepatomegaly/hepatocytomegaly and testicular artrophy with degeneration of the seminiferous tubular epithelium were also seen at 125 and 300 mg/kg/day. Hemosiderin-laden macrophages, congestion of the splenic red pulp, methemoglobin production indicative of the bone marrow toxicity suggested hemolysis as the mechanism of anemia.

Applicant's summary and conclusion

Conclusions:

The present study demonstrated that liver, testes and blood are the main target organs of TNT toxicity in the rats. Splenic lesions were also observed but were secondary to the hemolytic effect.