4-chloro-α,α,α-trifluoro-3-nitrotoluene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: in accordance with guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-α,α,α-trifluoro-3-nitrotoluene

EC Number:

204-451-6

EC Name:

4-chloro-α,α,α-trifluoro-3-nitrotoluene

Cas Number:

121-17-5

Molecular formula:

C7H3ClF3NO2

IUPAC Name:

1-chloro-2-nitro-4-(trifluoromethyl)benzene

Details on test material:

- Name of test material (as cited in study report): Mononitro
- Physical state: pale amber liquid
- Analytical purity: 99%
- Lot/batch No.: IS05-04/03/02
- Expiration date of the lot/batch: n.a. (receipt date 27 May 2003)
- Storage condition of test material: room temperature, in the dark

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: groups of five by sex in solid-floor polypropylene cages with stainless steel lids
- Diet : ad libitum (EU rodent diet 5LF2, IPS Ltd, Northants, UK)
- Water : ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12 hrs continuous light, 12 hrs darkness

IN-LIFE DATES: From: 22 September 2003 To: 09 October 2003

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The test material was aerosolised using a glass concentric jet nebuliser located at the top of the exposure chamber. the nebuliser was connected to a glass syringe attached to an infusion pump, which provided a continuous supply of test material under pressure, and to a metered compressed air supply.
compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebuliser.
The cylindrical exposure chamber had a volume of approx. 30 litres (dimensions: 28 cm diameter X 50 cm high). the concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump. The extract from the exposure chamber passed through a scrubber trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure.
Prior to the start of the study, test material atmospheres were genearted within the exposure chamber. During thic characterisation period, test material input rates were varied to achieve the required atmospheric concentrations.
the temperature and humidity inside the exposure chamber were measured by an electronic thermometer /humidity meter located in a vacant port in the animals' breathing zone of the chamber and recorded every 30 minutes throughout the 4-hour exposure period.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the particle size of the generated atmosphere inside the exposure chamber was determined 3 times during the expsoure period using a marple Personal Cascade impactor. it was as follows:
Mean Achieved Atmosphere Concentreation (mg/L): 5.18
Mean MAss Median Aerodynamic Diameter (µm): 4.00
Inhalable Fraction (% < 4 µm): 50.0
Geometric Standard Deviation: 2.15

CHAMBER FLOW RATE : 70 /h
THEORETICAL CHAMBER EQUILIBRATION TIME: 4 minutes (Silver, 1946)

Duration of exposure:

ca. 4 h

Concentrations:

Mean achieved Atmosphere Concentration : 5.18 mg/L

No. of animals per sex per dose:

10 animals in total (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights were recorded prior to treatment on the day of exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (hourly intervals during exposure, immediately on removing from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 days).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.18 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Males: 0/5
Females: 0/5
Total: 0/5

Clinical signs:

other: Signs of hunched posture and piloerection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded.These observations are considered to be associated with the restraint pr

Body weight:

One male animal showed a slight body weight loss in week 1 but recovered to show normal development in week 2. Normal development was recorded for all other animals.

Gross pathology:

No macroscopic abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No deaths occurred in a group of ten rats exposed to amean achieved atmosphere concentration of 5.18 mg/L for 4 hours. It was therefore considered that the acute inhalation median lethal concentration (4hr LC50) of MONONITRO in the Sprague- dawley Crl:CD (SD) IGS BR strain rat, was greater than 5.18 mg/L.

Executive summary:

A study was performed to assess the acute inhalation toxicity of the test material, as per OECD Guidelines n. 403.

A group of 10 Sprague-Dawley Crl:CD (SD) IGS BR strain rats (five males and five females) was exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a 14 day observation period.

The mean achieved atmosphere concentration was 5.18 mg/L, with a standard deviation equal to 0.49.

the characteristics of the achieved atmosphere were as follows:

Mean Achieved Atmosphere Concentreation (mg/L): 5.18

Mean MAss Median Aerodynamic Diameter (µm): 4.00

Inhalable Fraction (% < 4 µm): 50.0

Geometric standard Deviation: 2.15

The mortality data are sumarized as follows: Males: 0/5, Females:0/5, Total: 0/10.

Common abnormalities noted during the study included increased respiratory rate, hunched posture, piloerection and wet fur. there were occasional instances of laboured respiration and noisy respiration and isolated occurrences of lethargy, ataxia and sneezing. Animals recovered steadily to appear normal 2 or 3 days after exposure.

One male animal showed a slight body weight loss in week 1 but recovered to show normal development in week 2. Normal development was recorded for all other animals. No macroscopic abnormalities were detected at necropsy.