1-bromo-4-fluorobenzene

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: Data is from National Toxicology Program (NTP)

Justification for type of information:

Data is from National Toxicology Program (NTP)

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Acute oral toxicity study of test chemical in rats

Author:

National Toxicology Program (NTP)

Year:

2005

Bibliographic source:

National Toxicology Program (NTP)

Reference 2

Reference Type:

review article or handbook

Title:

Initial submission: Inhalation Median lethal concentration toxicity study with test chemical in Rats with cover letter

Author:

Haskell Laboratory

Year:

1986

Bibliographic source:

NTRL report No.88920004148

Reference 3

Reference Type:

secondary source

Title:

Provisional Peer Reviewed Toxicity Values for test chemical

Author:

U.S. Environmental Protection Agency

Year:

2017

Bibliographic source:

U.S. Environmental Protection Agency

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Acute inhalation toxicity study of test chemical in rats

GLP compliance:

not specified

Test type:

other: Single dose study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-bromo-4-fluorobenzene

EC Number:

207-300-2

EC Name:

1-bromo-4-fluorobenzene

Cas Number:

460-00-4

Molecular formula:

C6H4BrF

IUPAC Name:

1-bromo-4-fluorobenzene

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): 4-Bromofluorobenzene (INY-1059-1)
- Molecular formula (if other than submission substance): C6H4BrF
- Molecular weight (if other than submission substance): 175.0 g/mole
- Substance type: Organic
- Physical state: Clear coloureless to slightly yellow liquid

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New york
- Age at study initiation: 8 weeks old
- Weight at study initiation: 221 to 258 gm
- Housing: Animals were housed in a pair suspended, stainless steel, wire –mash cages with dimensions of 8” X 14” X 8” (wXdXh). Each rat was assigned lower number in each cage, identification by a slash in the right ear. Prior to being exposed rats tails and cage cards were colore- coded with warter insoluble markersso that individual rats coul be identified after exposure.
- Diet (e.g. ad libitum): Purina certified rodent chow #5002, except during exposure, ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 1 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2 °C
- Humidity (%): 50 ± 10%
- Photoperiod (hrs dark / hrs light): Timer-controlled, 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 2/8/85
To: 2/28/85

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

VEHICLE
- Concentration in vehicle: 7.1, 14, 19, 22 and 26 mg/L

DOSAGE PREPARATION (if unusual): Vapor atmospheres of INY-1059-1 were generated by metering with syringe drive onto the inner surface of a heated, 3-neck round bottom flash evaporation. Dilution air was added to the flask to sweep the vapors into glass 38 liter exposure chamber.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

7.1, 14, 19, 22 and 26 mg/L

No. of animals per sex per dose:

Total : 50
7.1 mg/L bw: 10 male
14 mg/L bw: 10 male
19 mg/L bw: 10 male
22 mg/L bw: 10 male
26 mg/L bw: 10 male

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and body weight were examined.

Statistics:

No data available

Results and discussion

Preliminary study:

No data available

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

18 mg/L air

Based on:

test mat.

95% CL:

> 15 - < 21

Exp. duration:

4 h

Remarks on result:

other: No effect on survival, clinical and body weight

Mortality:

At 22 mg/L and 26 mg/L, 6 and 10 male rats were dead, 3 at 19 mg/L bw, 4 at 14 mg/L and no effect on survival of 7.1 mg/L treated rats were observed.

Clinical signs:

other: Loss of righting reflex, diminished startle response, lethargy, tremors, spasms, labored or rapid breathing, red nasal discharge, and darkened eyes were observed in treated rats.

Body weight:

Slight -to-moderate body weight loss (up to 8%) was observed in rats exposed to 7.1 mg/L and a slight-to-severe weight loss (4.1- 17.5%) was observed in the rats exposed to 14 mg/L or greater. were observed in treated rats.

Gross pathology:

No data available

Other findings:

No data available

Any other information on results incl. tables

Sr no.	Dose rate	Average body weight	Emulsion concentration (mg/ml)	Average dose	Mortality ratio
1	1000	231(227-243)	225	1.0	0/10
2	2000	251(235-268)	300	1.7	1/10
3	3000	242(226-253)	300	2.4	7/10
4	5000	259(255-267)	300	4.3	10/10

 

Sr no.	Concentration mg/L			Mortality
	Mean	S.D	Range	Death/Exposed
1	7.1	0.27	6.8-7.5	0/10
2	14	1.2	12-16	4/10
	19	0.89	17-20	3/10
3	22	1.0	20-24	6/10
4	26	0.93	25-27	10/10

 

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

LD50 was considered to be 18 mg/L bw (15 – 21 mg/L) when Crl:CD (SD)BR male rats were exposed to test chemical by nose only inhalation.

Executive summary:

In acute inhalation toxicity study,Crl:CD (SD)BR male rats were treated with 4-Bromofluorobenzene (4-BFB) in the concentration of 7.1, 14, 19, 22 and 26 mg/L in air generated by metering with syringe drive onto the inner surface of a heated, 3-neck round bottom flash evaporation. Dilution air was added to the flask to sweep the vapors into glass 38 liter exposure chamber and observed for 14 days. 6 and 10 male rats were dead at 22 mg/L and 26 mg/L, 3 at 19 mg/L bw, 4 at 14 mg/L and no effect on survival of 7.1 mg/L treated rats were observed. Loss of righting reflex, diminished startle response, lethargy, tremors, spasms, labored or rapid breathing, dry red nasal discharge,incrased salivation,red ocular discharge,lung noise, darkened eyes,partially closed eyes, ruffled and discolored fur were observed in treated rats. Slight -to-moderate body weight loss (up to 8%) was observed in rats exposed to 7.1 mg/L and a slight-to-severe weight loss (4.1- 17.5%) was observed in the rats exposed to 14 mg/L or greater were observed in treated rats. Therefore, LD50 value was considered to be 18 mg/L bw in air(15 – 21 mg/L),when Crl:CD (SD)BR male rats were exposed to 4-Bromofluorobenzene (INY-1059-1)(460 -00 -4) by nose only inhalation.