α,α,α,4-tetrachlorotoluene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

March 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α,4-tetrachlorotoluene

EC Number:

226-009-1

EC Name:

α,α,α,4-tetrachlorotoluene

Cas Number:

5216-25-1

Molecular formula:

C7H4Cl4

IUPAC Name:

1-chloro-4-(trichloromethyl)benzene

Test animals

Species:

rat

Strain:

other: Sprague Dawley, albino, CD strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Kent
- Age at study initiation:6-7 weeks old on receipt
- Weight at study initiation: 176-196 g on receipt
- Housing: the rats were caged 5 males or 5 females to a cage.
- Diet: free access to a measured amount of food (Spratrt's Laboratory Diet 1)
- Water : free access to a measured amount of tap water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 and 22 °C in the two holding rooms.
- Humidity (%): 33%, (standard deviation 5.4).


IN-LIFE DATES: From: March 3, 1980 To: March 11, 1980

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

CHAMBER DESCRIPTION
The used chambers were of square section and fitted with pyramidal tops. The chambers were made of perspex and had an internal volume of approx. 0.13 m3. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments. the test atmosphere entered through a port at the base centre of the chamber and passed out through small holes in the lower edge of the square section. Each chamber was positioned inside a large glass walled cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.


INHALATION EXPOSURE
Three groups of ras were exposed continously for 4 hours to test atmospheres containing the test article. A fourth group acting as a control received clean air only for 4 hours.
A supply of clean dry air was connected to the aerosol generator and the supply pressure was adjusted to give a flow rate of 30 litres per minute measured at the generator outlet tube. A 10 or 100 ml glass syringe, filled with 4-chlorobenzotrichloride was fitted to the syringe pump and connected to the generator via a three-way PTFE tap and a lenght of PTFE tubing. A flow rate of between 0.13 and 0.90 ml per minute was selected for the exposure. the rats (5 males and 5 females) were placed into separate compartments of the expsoure chamber. the syringe pump was switched on and the exposure timed from the appearence of an aerosol from the generator outlet. the syringe was refilled as required during the exposure through the three-way tap.
After 4 hours the suppluy of test article was discontinued and the exposure chamber was allowed to clear for 60 minutes before the rats were removed for examination. The exposure procedure was repeated for each test group at a difefrent setting of the syringe pump or with a different syringe to obtain other flow rates of the test substance,.
Following exposure, the rats were kept in a ventilated cabinet for 48 hours and then returned to the holding room for the remainder of the observation period.


CHAMBER ATMOSPHERE
- Particle size distribution:
Stage 1: particles freater than 5.5 µm mean aerodynamic diameter (A.d.)
Stage 2: particles between 5.5 and 2.0 µm mean aerodynamic diameter
Stage 3: particles less than 2.0 µm mean aerodynamic diameter

The temperature in the exposure chamber was measured with a mercury bulb thermometer and recorded at 30 minute intervals during the exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

samples drawn through a gas absorption trap containing 15 ml of acetonitrile at a rate of 2 litres per minute.

Duration of exposure:

4 h

Concentrations:

0.99, 1.31, 2.32 g/m3 of chamber air.

No. of animals per sex per dose:

3 test groups, each of 5 male and 5 female rats.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

1.41 other: g/m3

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Standard error 0.18 g/m3

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

1.59 other: g/m3

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Standard Error 0.25 g/m3

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.48 other: g/m3

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Standard Error 0.13 g/m3

Mortality:

Control Group : 0/5
Group 1 (mean concentration 1.31 g/m3) : 1/5 males and 3/5 females
Group 2 (mean concentration 2.32 g/m3): 5/5 males and 4/5 females
Group 3 (mean concentration 0.99 g/m3): 1/5 males and 0/5 females

Clinical signs:

other: DURING EXPOSURE Normal appearance and behaviour for control group. Abnormal posture, lacrimation, salivation and peripheral vasodilation observed for groups exposed to 4-chlorobenzotrichloride. DURING OBSERVATION PERIOD Normal appearance and behaviour for

Body weight:

A loss of bodyweight over 3-4 days by all groups exposed to the test substance. Subsequent rate of bodyweight gain was irregular with a definite decrease in the rate of bodyweight gain towards the end of the observation period.

Gross pathology:

At the end of the 14 day observation period, the rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination. Findings for rats that died following exposure to the test substance were areas of hepatisation and bright red appearance of the lung and distended gas filled stomachs.
Findings for surviving rats were areas of hepatisation and numerous dark sub-pleural foci in the lung.

Other findings:

Food and water consumption by each cage of rats was daily measured from the day following arrival.

Applicant's summary and conclusion

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

LC50 (4 hour) = 1.4 g/m3 of air

Executive summary:

The acute inhalation toxicity of 4 -chlorobenzotrichloride was assessed by exposing 3 groups of rats for a period of 4 hours, to atmospheres containing a respirable aerosol of the test substance (whole body method). The study was performed with albino rats CD strain (SpragueDawley), females and males. One control group exposed to clean air was used too.

At the atmosphere concentartions of 0.99, 1.31 and 2.32 g/m3 of chamber air, the calculated LC50 resulted to be established at 1.48 g/m3 of air. Acute exposure to the aerosol, at the concentrations used for this study, produced irritation to the eyes and skin of the rat and had a marked injurious effect on the lungs and upper airways.