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Mechanism of action
Toxicity due to bromobenzene is most likely due to the biotransformation to reactive intermediates. It occurs when the rate of detoxification is lower than the rate of metabolism to these intermediates. Toxic effects in the liver and kidney have been studied. They have different underlying mechanisms. {following information: rats, in vivo}

Observed toxic effects in the centrilobular part of the liver are: inflammation, cytomegaly, necrosis and mineralization. More specifically were they observed in the central part of the hepatic lobules. However, for inflammation and mineralization it is questionable whether they count as the pathological result of exposure to bromobenzene, since inflammation was also seen in control rats and mineralization only occurred at a dose at which mortality also occurred. These thus have different mechanisms than cytomegaly and necrosis. Necrosis was observed at doses higher than those at which cytomegaly occurred, hence these may have the same underlying mechanism.

was seen in the control group as well as at doses at which no necrosis occurred hence this seems to be due to experimental factors. Furthermore, mineralization only occurred at a dosage at which

''There is some evidence to suggest a common mechanism of action for bromobenzene induced cytomegaly, necrosis, inflammation, and mineralization. All four lesions were principally observed in the central part of the hepatic lobules.''

Treatment of rats with either phenobarbital (a known CYP inducer), SKF 525A (a known CYP inhibitor), diethyl maleate (which depletes glutathione), or cysteine (a precursor of glutathione) showed the importance of GSH conjugation in the detoxification of bromobenzene.

''The underlying molecular mechanism of halobenzene hepatotoxicity was elucidated using Quantitative Structure-Activity Relationships (QSARs) and accelerated cytotoxicity mechanism screening (ACMS) techniques in rat and human hepatocytes. The in vivo and in silico studies suggest that halobenzene 43 interaction with cytochrome P-450 for oxidation is the rate limiting step for toxicity and is similar in both species.''

Synthesis
Bromobenzene can be formed by electrophilic aromatic substitution of benzene using bromine. This can be done in the absence of a catalyst using supercritical carbon dioxide (scCO2) as a solvent. As a Lewis acid, carbon dioxide facilitates the reaction by coordinating bromine atoms, which enhances both the electrophilicity of the brominating species and the ability of bromide as a leaving group. Bromobenzene can also be prepared from from benzene using bromine and iron in dichloromethane.

There are many other ways in which bromobenzene can be synthesized from benzene or from other molecules. Bromobenzene is prepared industrially by the action of bromine on benzene in the presence of iron powder.

Toxicity
Bromobenzene irritates the skin and is a central nervous system depressant in humans. Nothing is known about its chronic effects. The toxic effect in other species have been extensively studied. Liver, kidney, and lung have been identified as the target organs for this chemical by a variety of routes.4,1

Acute Toxicity
From animal experiments (mouse, rat, rabbit) it can be seen that when inhaled in higher concentrations (> 250 ppm) only microscopic damage to certain cell types of the respiratory tract tissue (Club cells in the bronchioles and distal bronchi) takes place, while deeper lung sections (alveolar cells type I and II) remain unaffected.

Similar tissue changes in the upper respiratory tract, e.g. in the olfactory mucosa, and also in lower respiratory tracts were equally observed when exposed intravenously, intraperitoneally or also orally.

Subchronic Toxicity
Intensive animal studies from the National Toxicology Program are available. In a 13-week inhalative study, rats were exposed to bromobenzene vapors through whole body exposure at 0, 10, 30, 100, or 300 ppm (6 hours/day, 5 days/week). Deaths did not occur. Except for irritations (i.a. Lacrimation) and apathy in the highest exposed group on the first day, no clinical poisoning symptom were registered. Liver and kidney weights were concentration dependent significantly increased. However the section did not reveal any histological liver tissue changes, even with the highest exposed animals.

A parallel study on mice conducted under analogous conditions gave similar results. Here, there was a significant increased incidence in the highest dose exposed group, of necrosis and mineralization in the liver tissue.

Lung damage was undetectable in both species even at 300 ppm. Based on the observed hepatomegaly in the above mentioned study, a margin of exposure (or MOE) was derived resulting in a reference concentration for the subchronic inhalative exposure of humans of 0.2 mg / m³.

Chronic Toxicity
No studies on health effects in animals following the chronic inhalation exposure to bromobenzene are available.