Dinitrotoluene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions (pure 2,6- dinitrotoluene tested; exposure for 6 h)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

6 h exposure

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dinitrotoluene

EC Number:

210-106-0

EC Name:

2,6-dinitrotoluene

Cas Number:

606-20-2

Molecular formula:

C7H6N2O4

IUPAC Name:

2-methyl-1,3-dinitrobenzene

Details on test material:

- Name of test material (as cited in study report): 2,6-dinitrotoluene
- Analytical purity: >99%
- Physical state: yellow solid
- Stability under test conditions: stable under normal conditions of use
- Storage condition of test material: in the dark at 4 °C

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

other: inhalation: vapour (lowest dose) and aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: vapour: clean dried air; aerosol: acetone/polyethylenglycol 200

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only exposure chambers made of perspex
- Exposure chamber volume: 50 L
- Method of holding animals in test chamber: perspex restraining tubes which were attached at evenly spaced ports in the chamber. Each rat was restained in a forward position by an adjustable plastic stopper which also provided a seal for the tube.
- Source and rate of air: 25 L/min
- System of generating vapour: The yapour generator was constructed from a 1 litre 2-necked flask, an air inlet tube and glass distillation column which connected the flask to the inlet port on the exposure chamber. The flask was maintained at approx. 90 °C in a hot water bath. The glass column connecting the flask to the exposure chamber was filled with glass wool to act as a particulate trap and also allowed the test atmosphere to coll to approx. 26 °C before entering the exposure chamber.
- System of generating particulates/aerosols: The aerosol generator was designed to produce and maintain an atmosphere containing a high proportion of respirable droplets. The generator (made of stainless steel or glass) was comprised af a concentric jet atomiser and a plastic elutriation column. The solution of test substance in acetone was supplied to the generator from a syringe driven at a constant rate by a syringe pump. The compressed air supply to the generator was dried, filtered and oil-free.
- Method of particle size determination:
- Treatment of exhaust air: absolute filter
- Temperature: 22 - 27 °C


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography fitted with a flame ionisation detector was used. The quatification was calibrated with prepared 2,6-DNT standard solutions.
- Samples taken from breathing zone: yes; seven air samples were taken during each exposure


VEHICLE
- Composition of vehicle (if applicable): acetone and polyethylen glycol 200
- Concentration of test material in vehicle: 15 g 2,6-dinitrotoluene (2,6-DNT) and 5 g polyethylene glycol 200 were dissolved in sufficient acetone to make 100 mL of solution.
- Justification of choice of vehicle: Polyethylene glycol 200 was necessary to eliminate crystalisation of 2,6-DNT at the tip of the concentric jet atomiser.


TEST ATMOSPHERE
- Particle size distribution: Approx. 25% of the paricles were smaller than 1.0 µm size. Approx. 87 - 96% of the 2,6-DNT present in the chamber atmosphere was in the form of respirable particles (< 5.5 µm).
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 1.7 - 2.0 µm/GSD 2.26 - 2.95

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

mean analytical concentrations: 0.026, 0.196, 0.473 and 0.694 mg/L air

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. Clinical signs were recorded at the end of the chamber equilibration period (5 min), at 0.25, 0.5 and 1 h and then at hourly intervals during the exposure. During the observation period the clinical signs were recorded once in the morning and then as necessary.
- Necropsy of survivors performed: yes; also all animals that died as a result of exposure
- Other examinations performed:body weight (daily), food and water consumption (dails), organ weights (lung), other: blood samples were taken from the orbital sinuses from all rats at approx. 24 h before exposure and then at 1, 24 and 48 h post exposure. The samples were analysed for methemoglobin using the method of Van Kampen and Zijlstra, 1975. Additional samples were taken at seven days post exposure for selected groups.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.43 mg/L air (analytical)

95% CL:

0.23 - 0.63

Exp. duration:

6 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

0.24 mg/L air (analytical)

95% CL:

0.08 - 0.4

Exp. duration:

6 h

Effect levels 3

Sex:

female

Dose descriptor:

LC50

Effect level:

0.66 mg/L air (analytical)

95% CL:

0.49 - 0.83

Exp. duration:

6 h

Effect levels 4

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.36 mg/L air

Exp. duration:

4 h

Remarks on result:

other: calculated from 6 h value (calculated value was adopted from the OECD SIDS 2004)