1-fluoro-2-nitrobenzene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - december 1978

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study well conducted, well described, following standard guidlines, but not under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-fluoro-2-nitrobenzene

EC Number:

216-088-0

EC Name:

1-fluoro-2-nitrobenzene

Cas Number:

1493-27-2

Molecular formula:

C6H4FNO2

IUPAC Name:

1-fluoro-2-nitrobenzene

Details on test material:

- Name of test material (as cited in study report): 2- fluoronitrobenzene
- Physical state: lemon yellow liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grmston, Hull.
- Housing: singly or 5 to a cage.
- Diet: Dixons 41B diet, ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: up to 10 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 2 °C
- Humidity: 50 +/- 5 %

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 100 l
- System of generating particulates/aerosols: A glass syringe is filled with the liquid sample and is connected to a concentric glass atomiser. By means of a palmer injection apparatus the liquid is injected at an even rate from the syringe through the atomiser into a current of filtered dry air. The air is obtained from an oil-free carbon ring compressor.The generated aerosol is passed through a contral glass column into a 100 l volume perspex exposure chamber. The cylindrical chamber of 49.5 cm diameter and 36.0 cm height rests on an aluminium alloy tray and is covered with a hemispheric perspex lid. The aerosol leaves the exposure chamber through a series of holes around the base of the chamber. The exposure chamber is placed inside an air extraction cabinet wich ventilates through a bag filter to the outside air by means of a centrifugal fan.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were monitored during the exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used:The concentration of the test item in the exposure chamber was monitored by collecting samples of test atmospheres from the breathing zone of the animals and examining the aerosol content of the samples by gas chromatography. (PerkinElemer 33 F33 Gas Cromatograph fitted wit F/D)
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Preliminary test: Nominal aerosol concentration during the first preliminary test was established initially at 1.00 mg/l. On the first day of exposure the concentration was increased at hourly intervals to 2.00 and 4.00 mg/l. On the second day the animals were subjected to a further 3-hour period of exposure at a nominal concentration of 5.00 mg/l.
Main test: 0.10, 0.50, 1.00, 2.80 and 10.00 mg/l air (nominal) / 0.10, 0.50, 0.93, 2.85 and 6.75 mg/l air (measured)

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were observed at intervals throughout the exposure period and each rats was individually inspected before and after exposure. The preliminary groups were weighed once before exposure and up to 3 times after. The control and test groups were weighed twice before exposure and on days 2, 4 8, 11, and 15 after exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Statistics:

The aerosol concentration likely to cause death in 50 % of the exposed rats during a period of 15 days following a 4 hours exposure period was calculated by the log-probit method (Miller, L.C. and Tainter, M.L. 1944, Proc. Soc. Exp. Biol & Med., Vol. 57 (2) 261).
The standard Error was calculated from the formula: S.E. = 2S/racine (2N). Where 2S is the estimated increment in dose levels necessary to increase the effects by 2 probits within the concentration range. These correspond to values at 16 % and 84 % mortality. By subtracting the former from the latter gives 2S. N is the total number of rats in the affected groups between 6.7% and 93.3 % mortality.

Results and discussion

Preliminary study:

Preiminary group 1: No signs of adverse response were seen in the 2 rats during the first hour of exposure, during the second hour eye and respiratory irritations were noted, during the third hour peripheral vasoconstriction was also observed. During the second day of exposure increased urinary secretion and lethargy were noted as well. Lethargy persisted on the day following the last exposure but the other adverse signs were absent.

Preliminary group 2: The adverse signs of response seen during exposure in the previous group of rats were also seen in this group but the signs were more severe. In addition the rats appeared to be comatose after 2 hour 30 minutes exposure. The female rat died 30 minutes after termination of exposure, its lung were pale grey in colour. The male rat was limp and lethargic, showed uncoordinated movements, end its fur was stainded yellow around the urethra and on its posterior ventral area.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.26 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Group 5: At 2.85 mg/l, 4 males and 2 females died between day 1 to 2. One male and 1 female rat died 15 and 30 minutes respectively after termination of exposure; 2 further males and 1 female rat died overnight following exposure, and 1 male died during the day following exposure.

Group 6: At 6.75 mg/l, 3 males and 4 females died between day 1 to 2. Two female rats died during exposure: 3 hour 30 minutes and 3 hour 50 minutes after the start of exposure. One male and one female rat died 45 minutes after termination of exposure, and 2 further males and 1 female rat died overnight following exposure

Clinical signs:

other: Group 1 (control): The behaviour of rats was normal during the 4-hour exposure period and during the subsequent 15-day observation period. Group 2 (0.10 mg/l): The behaviour of this group of rats during and after exposure was similar to that of the contr

Body weight:

Group 1 (control): The rate of growth was within limits of normal variation for this strain and age of rats.

Group 2 (0.10 mg/l): The rate of growth was similar to those of the control group.

Group 3 (0.50 mg/l): Both sexes of rats lost weight on the day following exposure; the rate of growth was normal subsequently.

Group 4 (0.93 mg/l): The animals lost weight during the first 4 days after exposure.

Group 5 (2.85 mg/l): They lost weight during the first week of post-exposure observation, the rate of growth was normal during the second week.

Group 6 (6.75 mg/l): Animals lost weight during the first week after exposure but the rate of growth was normal during the second week.

Gross pathology:

Group 1 (control): During macroscopic examination all organs and tissues appeared to be normal.

Group 2 (0.10 mg/l): Areas of darker colour were seen on the surface of the lungs of 2 male and 2 female rats. Such discolouration frequently occurs on the lungs of laboratory rats and therefore no toxicological importance is attached to this finding.

Group 3 (0.50 mg/l): Macroscopic pathology revealed areas discolouration on the surface of lungs of 3 male and 2 female rats, no toxicological importance is attached to this finding.

Group 4 (0.93 mg/l): Macroscopic examination of the major internal organs revealed no abnormalities.

Group 5 (2.85 mg/l): On dissection the lung parenchyma appeared to be very pale and bloodless with sharply defined congested areas containing brown coloured blood. The bladder contained urine stained as the colour of the test item. In one male rat the liver and kidney showed lobular changes in colour and the bladder contained brown urine. No abnormalities were seen in any of the major internal organs during macroscopic pathology in surviving animals.

Group 6 (6.75 mg/l): Dead animals: on dissection the lung parenchyma appeared pale grey and bloodless with sharply defined areas of congestion containing blood of brown colour. The bladder contained urine of the colour of test item. Surviving animal: macroscopic patology revealed sharply defined areas of congestion in the lungs of the 2 surviving male rats.

Any other information on results incl. tables

Table 1: Mortality in rats exposed to the aerosol of 2 -fluoronitrobenzene.

Dose level (mg/l)	Deaths by day (5 M/5 F)		Total death (combined male and female)	Percentage Mortality (%)
	Day 1	Day 2
0	0M/0 F	0M/0 F	0	0
0.10	0M/0 F	0M/0 F	0	0
0.50	0M/0 F	0M/0 F	0	0
0.93	0M/0 F	0M/0 F	0	0
2.85	1M/1F	3M/1F	6	60
6.75	1M/3F	2M/1F	7	70

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the experimental conditions of this test, the test item is classified as Acute Inhal. Tox. cat. 4, H 332 (Harmful if inhaled) according to CLP.

Executive summary:

Five groups of 10 rats were exposed for 4 hours to the aerosol of 2 -fluoronitrobenzene at concentrations of 0.10, 0.50, 0.93, 2.85 and 6.75 mg/l air. The animals were subsequently observed for 15 days. Mortality, eye and respiratory irritations, dyspnoea, bradypnoea, torpor and coma were observed in the animals during and after exposures. Temporary loss in body weights were noted after exposure. Macroscopic pathology revealed congestion and discolouration of the lungs in rats exposed to the 2 highest aerosol concentrations. The calculated LC50(4h) was located at 2.26 (+/- 0.42) mg/l air. The threshold of response was located between 0.10 mg and 0.50 mg of 2 -fluoronitrobenzene per litre air. It is concluded that under experimental conditions described in this report aerosols generated from the sample of 2 -fluoronitrobenzene have adverse effects on the respiratory, nervous and circulatroy systems as well as local effects on the eye of rats. Therefore, the test item is classified as , cat. 4, H 332 (Harmful if inhaled) according to CLP.