1-bromo-4-fluorobenzene

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for target chemical 1-bromo-4-fluorobenzene (CAS No. 460-00-4) was considered based on experimental study conducted on rats. The LD50 value was considered in between > 2000 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, 1-bromo-4-fluorobenzene cannot be classified for acute oral toxicity.

Acute Inhalation toxicity:

In Acute inhalation toxicity, LD50 value for target substance 4-Bromofluorobenzene (460-00-4) was considered to be >18000 mg/m3 and >5950 mg/m3 in air in rat. All these studies concluded that the LD50 value is greater than 5 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Bromofluorobenzene (460-00-4) cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) for target 1-bromo-4-fluorobenzene (CAS No. 460-00-4) was considered based on experimental study conducted on rats, the value was considered to be >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 1-bromo-4-fluorobenzene (CAS No. 460-00-4) cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Acute oral toxicity study of test chemical in rats

GLP compliance:

not specified

Test type:

other: Single dose acute oral toxicty

Limit test:

no

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
- Housing: Animals were housed singly in suspended, stainless steel, wire –mash cages with dimensions of 8” X 14” X 8” (wXdXh). Each rat was assigned a unique identification number which was recorded on a card affixed to the cage.
- Diet (e.g. ad libitum): Purina certified rodent chow #5002, ad libitum
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 8 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: 3/20/85
To: 5/22/85

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1000, 2000, 3000 and 5000 mg/kg bw
- Justification for choice of vehicle: Marola corn oil

DOSAGE PREPARATION (if unusual): 4-Bromofluorobenzene (4-BFB) as emulsion in Marola corn oil.

Doses:

1000, 2000, 3000 and 5000 mg/kg bw

No. of animals per sex per dose:

Total : 40
1000 mg/kg bw: 10 male
2000 mg/kg bw: 10 male
3000 mg/kg bw: 10 male
5000 mg/kg 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:

LD50 values were calculated from the mortality data using method of 0.0.Finney.

Sex:

male

Dose descriptor:

LD50

Effect level:

2 700 mg/kg bw

Based on:

test mat.

95% CL:

> 2 200 - < 3 200

Remarks on result:

other: No effect on survival, clinical and body weight

Mortality:

At 3000 mg/kg and 5000 mg/kg bw, 7 and 10 male rats were dead, 1 at 2000 mg/kg bw and no effect on survival of 1000 mg/kg bw treated rats were observed.

Clinical signs:

other: Tremor, Limpness change in motor activity, clear discharge from eyes and ataxia were observed in treated rats.

Gross pathology:

No data available

Other findings:

No data available

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

Interpretation of results:

other: Not classified

Conclusions:

LD50 was considered to be 2700 mg/kg bw (2200 – 3200 mg/kg ) when Crl:CD (SD)BR male rats were treated with test chemical orally by gavage.

Executive summary:

In a acute oral toxicity study,Crl:CD (SD)BR male rats were treated with test chemical in the concentration of 1000, 2000, 3000 and 5000 mg/kg bw as emulsion in Marola corn oil orally by gavage and observed for 14 days. 7 and 10 male rats were dead at 3000 mg/kg and 5000 mg/kg bw, 1 at 2000 mg/kg bw and no effect on survival of 1000 mg/kg bw treated rats were observed. Tremor, Limpness change in motor activity, clear discharge from eyes and ataxia were observed in treated rats. Slight to sever decrease in body weight were observed in treated rats. Therefore,LD50 was considered to be 2700 mg/kg bw(2200 – 3200 mg/kg ) whenCrl:CD (SD)BR male rats were treated with test chemical orally by gavage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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)

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

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

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

Preliminary study:

No data available

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

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is summarized based on the available information from various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

WoE report is based on 3 acute dermal toxicity studies as - WoE 2 ,WoE 3 and WoE 4.
Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Species:

other: 2) Rabbit 3)Rabbit 4) Rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: 2)Dermal 3)Dermal 4)Dermal

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

2) >2000 mg/kg bw
3) 10000 mg/kg bw
4) >4000 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

10 000 mg/kg bw

Based on:

test mat.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 4 000 mg/kg bw

Based on:

test mat.

Mortality:

2) NO mortality observed
3) Mortality observed on dose level of 10000 mg/kg bw
4) NO mortality observed

Clinical signs:

other: Not specified

Gross pathology:

Not specified

Other findings:

Not specified

Interpretation of results:

other: Not classified

Conclusions:

According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.

Executive summary:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and rabbits for test chemical. The studies are summarized as below –

1.In acute dermal toxicity study, rabbit were treated withtest chemicalin the concentration of 2000 mg/kg bw by dermal application.No mortality was observed in treated rabbit at dose 2000 mg/kg bw.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rabbit were treated withtest chemicalby dermal application.

2. Acute dermal toxicity study was done in rabbits usingtest chemical.No mortality was observed at dose 10000 mg/kg bw. HenceThe LD50 value was considered to be >10000 mg/kg bw,when rabbits were treated withtest chemical by dermal application.

3.Acute dermal toxicity study of test chemical was conducted on rats at the dose concentration of 4000 mg/kg bw. All animals were maintained under close observation for recording toxic signs and time of death . No mortality was observed at 4000 mg/kg bw dose.Therefore, LD50 value was considered to be >4000 mg/kg bw, when rats were treated with test chemical via dermal application.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from authoritative database.

Additional information

Acute toxicity: Oral

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical 1-bromo-4-fluorobenzene. The studies are summarized as below –

In an acute oral toxicity study, Crl:CD (SD)BR male rats were treated with test chemical in the concentration of 1000, 2000, 3000 and 5000 mg/kg bw as emulsion in Marola corn oil orally by gavage and observed for 14 days. 7 and 10 male rats were dead at 3000 mg/kg and 5000 mg/kg bw, 1 at 2000 mg/kg bw and no effect on survival of 1000 mg/kg bw treated rats were observed. Tremor, Limpness change in motor activity, clear discharge from eyes and ataxia were observed in treated rats. Slight to sever decrease in body weight were observed in treated rats. Therefore, LD50 was considered to be 2700 mg/kg bw (2200 – 3200 mg/kg) when Crl:CD (SD)BR male rats were treated with test chemical orally by gavage.

 

Above studies was supported by the second and third study from other authoritative databases. In an acute oral toxicity study, rats were treated with test chemical in the concentration of 2248 mg/kg bw orally. 50 % mortality were observed in treated rats at 2248 mg/kg bw. Tremor, change in motor activity, and ataxia were observed in treated rats. Therefore, LD50 was considered to be 2248 mg/kg bw when rats were treated with test chemical orally.

 

In a acute oral toxicity study, rats were treated with test chemical in the concentration of 3788 mg/kg bw orally. 50 % mortality were observed in treated rats at 3788mg/kg bw. Tremor, change in motor activity, and ataxia were observed in treated rats. Therefore, LD50 was considered to be 3788 mg/kg bw when rats were treated with test chemical orally.

 

Based on the results of the present study, the LD50 value of the given test chemical is >2000 mg/kg bw. Thus, the test item is not classified for acute oral toxicity. CLP criteria "Not classified".

 

Acute Inhalation Toxicity: 

In different experimental studies4-Bromofluorobenzene (460-00-4)have been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for4-Bromofluorobenzene (460-00-4)along with the study available on structurally similar read across substance. The studies are summarized as below -

The experimental study mentioned in authoritative database for the target chemical4-Bromofluorobenzene (460-00-4)was designed and conducted for acute inhalation toxicity.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.

The above study is supported by another experimental study mentioned in secondary source for the target chemical 4-Bromofluorobenzene (460 -00 -4) was designed and conducted for acute inhalation toxicity.In acute inhalation toxicity study,Wistar male and female rats were treated with Para- Bromofluorobenzene in the concentration of 0 and 5.95 mg/L vapors generator constructed from a stainless steel atomizer and glass elutriator. Exposures were of square section and were fitted with pyramidal tops. 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.No effect on survival of treated male and female rats was observed. Mildly irritant vapor and included abnormal respiratory pattern and body posture. During the post exposure observation period, signs included abnormal respiratory pattern and fascicular tremors. Four of five female rats exposed to p-bromofluorobenzene developed hair loss from the back during the observation period, compared to a single female with hair loss from the head were observed in treated male and female rats as compared to control. Similarly, No effects on body weight, Food and water consumption of treated male and female rats were observed as compared to control. In addition, No effects on lung weight, gross pathology and Histopathology of treated male and female rats were observed as compared to control. Therefore,LD50 value was considered to be >5.95 mg/L bw in air,when Wistar male and female rats were exposed to Para- Bromofluorobenzene (460 -00 -4) by whole body inhalation for 4 hours. 

Thus, based on the above summarised studies on 4-Bromofluorobenzene (460 -00 -4), it can be concluded that LD50 value is >5 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4-Bromofluorobenzene (460 -00 -4) cannot be classified for acute inhalation toxicity.

 

 

Acute toxicity: Dermal

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and rabbits for test chemical. The studies are summarized as below –

 

In the first acute dermal toxicity study, rabbit were treated with test chemical in the concentration of 2000 mg/kg bw by dermal application. No mortality was observed in treated rabbit at dose 2000 mg/kg bw. Therefore, LD50 value was considered to be >2000 mg/kg bw, when rabbit were treated with test chemical by dermal application.

 

Similar acute dermal toxicity study was done in rabbits using test chemical. No mortality was observed at dose 10000 mg/kg bw. Hence the LD50 value was considered to be >10000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

 

Similarly in the third study acute dermal toxicity study of test chemical was conducted on rats at the dose concentration of 4000 mg/kg bw. All animals were maintained under close observation for recording toxic signs and time of death. No mortality was observed at 4000 mg/kg bw dose. Therefore, LD50 value was considered to be >4000 mg/kg bw, when rats were treated with test chemical via dermal application.

 

Thus, based on the above summarized studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on 4-Bromofluorobenzene (4-BFB) (CAS no.: 460-00-4) and it’s structurally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity.Thus, comparing this value with the criteria of CLP regulation,4-Bromofluorobenzene (4-BFB) (CAS no.: 460-00-4)cannot be classified for acute oral ,inhalation and dermal toxicity.