2-chloro-4-nitrotoluene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-4-nitrotoluene

EC Number:

204-501-7

EC Name:

2-chloro-4-nitrotoluene

Cas Number:

121-86-8

Molecular formula:

C7H6ClNO2

IUPAC Name:

2-chloro-1-methyl-4-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): 2-Chlor-4-nitrotoluol rein krist.
- Purity: 99.4 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann (Borchen, Germany)
- Age at study initiation: ca. 2-3 months
- Weight at study initiation: 170-210 g
- Housing: 5 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): ca. 40-60
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: polyethylene glycol 400/ethanol (1:1)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: plastic inhalation chamber
- Exposure chamber volume: about 20 l
- Method of holding animals in test chamber: Plexiglas exposure tubes
- Source and rate of air: compressed air was supplied by Boge compressors; ca. 45 air exchanges per hour
- Method of conditioning air: air was conditioned (i.e. freed from water, dust, and oil) automatically by a VIA compressed air dryer
- System of generating particulates/aerosols: by means of a nozzle and compressed air
- Method of particle size determination: samples for the analysis of the aerodynamic particle-size distribution were taken in the vicinity of the breathing zone. These samples were taken using a TSl-Laser Velocimeter APS 3300, including diluter TSI Model 3302 (TSI Inc., St. Paul, MN, USA).

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric and GC analysis
- Samples taken from breathing zone: yes

RESULTS OF PARTICLE-SIZE ANALYSES
- Particle size distribution: 100 % of particles were <= 3 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.34 µm / 1.41

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

analytical concentration: 528 mg/m³ air (maximum producible concentration)

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: several times on the day of exposure as well as at least twice daily during observation period (clinical signs, mortality); body weights were recorded immediately prior to exposure, on days 3, 7 and 14 thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: methemoglobin

Statistics:

LC50 calculation:
According to A.P. Rosiello, J.M. Essigmann and G.N. Wogan (J. Tox. and Environ. Health 3, 797 -809, 1977). This method is based on the Maximum likelyhood method of C.I. Bliss (Q. J. Pharm. Pharmacol. 11, 192 -216, 1938).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 528 mg/m³ air

Exp. duration:

4 h

Mortality:

All male and female animals survived the treatment.

Clinical signs:

other: No clinical signs were observed in both sexes.

Body weight:

Body weight development was slightly impaired up to day 3 of the 14-day post observation period in males and females.

Gross pathology:

The necropsies performed at the end of the study revealed no findings in male and female animals.

Other findings:

No substance-induced increase of methemoglobin concentration was noticed.

Applicant's summary and conclusion

Executive summary:

The inhalation LC50 in male and female rats was determined to be > 528 mg/m3 ( highest concentration that was technically achievable) for a 4 hour exposure (aerosol) to 2-Chlor-4-nitrotoluol rein krist. according to OECD TG 403. The test concentration of 528 mg/m3 revealed no mortality. No clinical signs and no substance-induced increase of methemoglobin concentrations were observed in both sexes. Body weight development was slightly impaired up to day 3 of the 14-day post observation period in males and females.