2,4,6-trinitrotoluene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 Apr 1974 - 31 May 1975

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Objective of study:

absorption

metabolism

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.36 (Toxicokinetics)

GLP compliance:

no

Remarks:

no (The study was conducted in 1975 whereas OECD and EU Guidelines as well as GLP Principles were implemented in 1981 and 1988)

Test material

Test material information

Constituent 1

Reference substance name:

TNT

IUPAC Name:

TNT

Constituent 2

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:

TNT was purchased from K&K Laboratories (Cleveland, Ohio). Purity >99%.

Radiolabelling:

yes

Remarks:

14C-labeled nitrotoluenes

Test animals

Species:

rat

Strain:

other: Charles River CD

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Duration and frequency of treatment / exposure:

24 hours/ administered once

Doses / concentrations

Remarks:

Doses / Concentrations:
test material suspended in peanut oil was administered in volume of 1 ml/100g bw (approx. 1/10 of the LD50)

Control animals:

not specified

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The nitrotoluenes were readily absorbed after oral administration in the rat. The absorption was essentially completed in 24 hours with approximately 60 to 90% of the aministered doses. The extents of absorption were in the fillowing order: 2,4-DNT, 3,4-DNT > TNT, 2,5-DNT > 2,3-DNT, 2,6-DNT.

Details on distribution in tissues:

The liver and kidney contained small but significant amounts of radioactivity. Very small amounts of radioactivity were also found in the other tissue including brain, lungs, skeletal muscle, and/or spleen.The tissue to plasma radioactivity ratios indicated that the nitrotoluenesand/or their metabolites were, in general, readily taken into most tissues.

Details on excretion:

Most of the absorbed radioactivity from oral administration of nitrotoluenes were excreted in the urine. It indicated that these compounts were extensively metabolised in the body since nitrotoluenes are water insoluble. The aromatic ring of these nitrotoluenes remained intact.

Metabolite characterisation studies

Details on metabolites:

TLC analysis of the urine from treated rats indicated that the nitrotoluenes were metabolised extensively. Unchanged parent compunds were not present in the urine.The urinary metabolites consisted of one or two classes of polar metabolites. TLC analysis of brain extracts from TNT treated rats revealed a radioactive nonpolar metabolite. However this did not correspond to TNT.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: low bioaccumulation potential based on study results.
The absorption in 24 hours is 60 to 90% of the aministered doses. Nitrotoluenes are extensively metabolised in the body since they are water insoluble