Fluorobenzene

Endpoint summary

Description of key information

Oral: LD50 = 7593.75 mg/kg bw (f); mouse; similar to OECD TG 423; GLP not specified; K2 

Inhalation: LC50 ≥ 24.7 mg/L (male); rat; similar to OECD TG 403; GLP; K2 

Dermal: no data available

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:

other: Well documented study which meets basic principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

not specified

Test type:

acute toxic class method

Species:

mouse

Strain:

ICR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Qinglongshan Animal Breeding Center of Nanjing, Jiangsu
- Age at study initiation: 6 weeks old
- Weight at study initiation:20.0 +/- 2.0g
- Fasting period before study: 3h
- Housing:Mice were caged in groups of ten using dust-free poplar chips for bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0 +/- 1 °C
- Humidity (%): 55.0 +/- 5 %
- Air changes (per hr): 10 times/h
- Photoperiod (hrs dark / hrs light): 12/12 h light/dark cycle

Route of administration:

oral: gavage

Vehicle:

other: maize germ oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.1 to 0.2 mL/100g
- Rationale for the selection of the starting dose: The preliminary experiment: Four dose levels 100, 500, 2000, 5000 mg/kg bw amd three mice for each level were used. The general concentration range was determined after observation of death and evident toxicity in 7 days. Then the administration doses were graded with geometric progression for ease of the calculation of LD50.

Doses:

0, 3375.0, 5062.5, 7593.8 mg/kg bw

No. of animals per sex per dose:

10 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes

Statistics:

The data on organ/body coefficients and hepatic antioxidantive responses were statistically analyzed using the SPSS software package Version 12.0 for Windows (SPSS Company, CHicago, IL). Data were expressed as the mean+/-standard deviation (SD). All the analyzed parameters were checked for assumptions of normality using the Kolmogorov-Smirnov and homogeneity of variance using the Levene test, respectively. The differences between the control and experimental group were analyzed using one-way analysis of varinace followed by Dunnett's test. Differences were considered significant at p>0.05 and highly significant at p<0.01.

Sex:

female

Dose descriptor:

LD50

Effect level:

7 593.75 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in the low dose group, in the mid dose goup 2 animals died and in the highest dose group 4 animals died.

Clinical signs:

convulsions

Body weight:

lower than 10% body weight loss

Remarks:

No statistically significant changes were observed.

Other findings:

Exposure results in slight pathological changes in mouse liver.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

7 593.75 mg/kg bw

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Groups of 6 male Crl:CD BR rats were exposed to vapor atmospheres of fluorobenze for a single 4-hour period.

GLP compliance:

yes

Test type:

other: Inhalation Approximate Lethal Concentration procedure

Limit test:

no

Species:

rat

Strain:

other: Crl:CD BR

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
- Weight at study initiation: 229-269 g
- Housing: single housing in suspended, stainless steel, wire-mesh cages; during the test, rats were housed in pairs.
- Diet: Purina Certified Rodent Chow #5002 ad libitum (except during exposure)
- Water: ad libitum (except during exposure)
- Acclimation period: rats were quarantined for one week upon receipt; afterwards, they were held in stock for up to one week prior to testing

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

other: air

Details on inhalation exposure:

EXPOSURE PROTOCOL:
For each exposure, 6 rats were individually restrained in perforated, stainless steel cylinders with conical nose pieces. The restrainers were inserted into a face plate on the exposure chamber such that only-the nose of each rat protruded into the chamber. Each group of 6 rats was exposed nose-only for 4 continuous hours to a vapor atmosphere of fluorobenzene in air.

ATMOSPHERE GENERATION:
Vapor atmospheres of fluorobenzene were generated by pumping the liquid test material with a Harvard Model 975 Compact Infusion Pump into a 3-neck glass mixing flask. The flask was heated to 84-93°C with a Briskeat Model BC-170 heater to facilitate evaporation. The flask temperature was controlled with a Teco Model TC-1000 controller and was monitored with an Omega Type K Thermocouple Thermometer. Air introduced at the flask (approximately 22 L/min) swept the fluorobenzene vapors through a glass dispersion funnel and into the exposure chamber. Additional dilution air (approximately 1-18 L/min depending on desired concentration) was added to the vapor mixture prior to its entry into the chamber. The chamber exhaust was drawn through a dry ice cold trap and a MSA cartridge filter prior to being vented into the hood.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by gas chromatography approx. every 30 min during exposure

Duration of exposure:

4 h

Concentrations:

50, 520, 3700, 6200 and 10000 ppm

No. of animals per sex per dose:

6 males per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were weighed and observed prior to exposure. Group observations of clinical signs of toxicity were taken during each exposure and when rats were released from restrainers after exposure. Surviving rats were weighed and observed daily for 14 days post exposure, weekends and holidays included when warranted by the rats' condition.
- Necropsy of survivors performed: no

Sex:

male

Dose descriptor:

other: Approximate Lethal Concentration

Effect level:

6 200 ppm

Exp. duration:

4 h

Remarks on result:

other: equivalent to 24.7 mg/L

Sex:

male

Dose descriptor:

LC50

Effect level:

> 6 200 ppm

Exp. duration:

4 h

Remarks on result:

other: equivalent to 24.7 mg/L

Mortality:

Two of 6 rats exposed to 6200 ppm and 5 of 6 rats exposed to 10,000 ppm died during exposure.

Clinical signs:

other: Please see any other information for description.

Body weight:

During the postexposure period, no significant weight loss or adverse clinical signs were observed in rats that survived exposure to fluorobenzene. No adverse clinical signs and average weight losses of 2% or less of initial body weight were observed in rats exposed to 50, 520 or 6200 ppm. Rats exposed to 3700 ppm were not weighed and observed one day after exposure. However, 3 of 6 rats had lost an average of 3% of initial body weight on the 2nd day post exposure, and no adverse clinical signs were observed. The one rat that survived exposure to 10,000 ppm had a dry red ocular discharge and lost 5% of initial body weight one day after exposure.

Concentration of fluorobenzene vapour atmospheres and rat mortality:

Concentration (ppm)			Mortality (# deaths/# exposed)
Mean	SD	Range
50	8.3	40-61	0/6
520	17	500-550	0/6
3700	1100	2000-6000	0/6
6200	630	5400-7400	2/6
10000	740	8800-11000	5/6

 

CLINICAL SIGNS

During or immediately following exposure, rats exposed to 50, 520 or 6200 ppm had red nasal or ocular discharges, effects common to rats under restraint. Rats exposed to 10,000 ppm had no response to sound during exposure. When released from restrainers after exposure, rats exposed to 3700 ppm and rats that survived exposure to 6200 or 10,000 ppm had rapid breathing, tremors, spasms, no righting reflex and clear oculardischarge.

Interpretation of results:

GHS criteria not met

Conclusions:

The ALC for fluorobenzene was 6200 ppm (equally to 24.7 mg/L). The TS is considered to have very low toxicity on an acute inhalation basis (ALC > 5000 ppm).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

>= 24.7 mg/L air

Physical form:

inhalation: vapour

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

Based on the available data, a classification for oral toxicity is not justified under Regulation No. 1272/2008, as amended for the seventeenth time in Regulation (EC) No. 2021/849.

The available studies on acute toxicity by inhalation are not suitable to assess this route of exposure but the results suggest a LC50 value greater than 20 mg/L.