Fluorobenzene

Endpoint summary

Description of key information

In accordance with the section 8.1.1 of Annex VIII of Regulation (EC) No 1907/2006 (REACH), the toxicokinetic profile of the substance (i.e. absorption, distribution, metabolism and elimination) was derived from the relevant available information collated in the dossier. The physical chemical characteristics of the target substance and the source substance, the results obtained from acute, repeated-dose, and reproductive toxicity studies, as well as information gained from genotoxicity assays were used to predict its toxicokinetic behaviour.

 

 

 

Physical-chemical properties:

 

Fluorobenzeneis a colourless liquid with a molecular weight of 96.1 g/mol and a water solubility of 1.54 g/L at 30 °C. The substance has a low vapour pressure of 30.3 Pa at 25 °C and the log Pow is 2.27 at 25 °C.

 

 

Absorption:

 

The physical chemical characteristics described above suggest that the target substance is of adequate molecular size to participate in endogenous absorption mechanisms within the mammalian gastrointestinal tract.Being lipophilic, the target substance may be expected to cross gastrointestinal epithelial barriers even if the absorption may be limited by the inability of the substance to dissolve into gastro-intestinal fluids and hence make contact with the mucosal surface.

 

These hypotheses are supported by oral systemic effects, as summarized below:

 

 

-One acute oral toxicity study was performed with Fluorobenzene (BG Chemie, 1998). The calculated LD50 value in rats was 9 455 mg/kg bw. This study conducted on this substance identified neither mortality nor clinical signs( LD50 > 2000 mg/kg bw).

 

- A repeated dose study conducted on this substance using the oral route gave a NOAEL of >200mg/kg bw/day.Changes observed in liver and kidneys in the 90-day study were considered as a normal adaptive metabolism/excretion response following administration of a xenobiotic. In the absence of corroborative pathology or functional change of the organs these changes are considered not to be adverse. No treatment-related effects were observed in any of these studies.

 

In light of these data, and the lack of specific information on any the registered substance or its supporting substances, the registered substance was assumed to be bioavailable by oral route for the purpose of human health risk assessment.

 

 

 

Dermal absorption

 

Regarding dermal absorption, this substance log Pow = 2.27, the rate of uptake into the stratum corneum is expected to be high while the rate of penetration is likely to be limited by the rate of transfer between the stratum corneum and the epidermis.There is no experimental data on the effects of acute or long-term Dermal exposure to the test substance available.

 

 

Respiratory absorption

 

Fluorobenzeneis a liquid with high vapour pressure (81 hPa at 20 °C) and the boiling point is 84.5℃, and therefore is medium volatility. Consequently, under normal use and handling conditions, inhalation exposure and availability for respiratory absorption of the substance in the form of vapour, gases or mists is possible (ECHA, 2014). The log Pow and water solubility indicate that Fluorobenzene may be absorbed across the respiratory tract epithelium to a certain extent. There is no experimental data on the effects of acute or long-term inhalation exposure to the test substance available.

 

In light of these data, and the lack of specific information on respiratory absorption, the substance was conservatively assumed to be 100% bioavailable by inhalation for the purposes of human health risk assessment.

 

 

 

Excretion:

 

Fluorobenzene, having a molecular weight lower than 300 g/mol, is expected to be mainly excreted in urine and no more than 5-10% may be excreted in bile. Any substance that is not absorbed from the gastro-intestinal tract, following oral ingestion, will be excreted in the faeces.

In summary, ACD/ADME and DS/ADMET were respectively applied to predict the TK properties of Fluorobenzene. Based on the predicted results from two different software in combination with reported experimental data of Chlorobenzene, this compound could be absorbed in small intestine and not pass the BBB easily and rapidly. This compound possesses good oral bioavailability. Furthermore, it could not bind with plasma protein tightly in blood and is not an inhibitor of P-gp and CYP450. Moreover, the compound would be metabolized to bep-fluorophenol ando-fluorophenol, and the produced metabolites may be excreted by the urine.