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Toxicological information

Repeated dose toxicity: oral

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981
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

Reference
Name:
Unnamed
Type:
Constituent
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

open allclose all
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
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.