Registration Dossier

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

1,2-dichlorobenzene is readily absorbed by ingestion and inhalation and widely distributed in the body particularly to the adipose tissue, the liver and kidneys. The biological residence time is short with complete excretion, predominately in the urine, generally occurring within 48 hours of exposure. The metabolism of 1,2-dichlorobenzene by rats occurs by hepatic cytochrome P450 enzymes (CYP2E1 and CYP2B1/2) and in humans by CYP2E1 only, with the initial formation of epoxide intermediates. 

Key value for chemical safety assessment

Additional information

1,2-dichlorobenzene is readily absorbed by ingestion and inhalation and widely distributed in the body particularly to the adipose tissue, the liver and kidneys. The biological residence time is short with complete excretion, predominately in the urine, generally occurring within 48 hours of exposure. The metabolism of 1,2-dichlorobenzene by rats occurs by hepatic cytochrome P450 enzymes (CYP2E1 and CYP2B1/2) and in humans by CYP2E1 only, with the initial formation of epoxide intermediates. The metabolic fate of the epoxides can be conjugation with glutathione, hydrolysis by epoxide hydrolase to dihydrodiols or rearrangement to form dichlorophenols. Subsequent oxidation of the dichlorophenols results in the formation of hydroquinone derivatives, which can further oxidise to benzoquinones. Metabolic differences exist between rats and humans with respect to the kinetics and profile of metabolites produced from 1,2-dichlorobenzene. The rank order for the kinetics of 1,2-dichlorobenzene metabolism by hepatic microsomes is human > rat. The formation of reactive epoxides and hydroquinone/benzoquinone species correlates with covalent binding and hepatotoxicity. The addition of glutathione to rat microsomes diminished covalent binding with concomitant increased formation of the GSH-conjugates indicating that in the rat, epoxides are important reactive metabolites. Human metabolism of 1,2-dichlorobenzene, as determined by hepatic microsomal metabolism, results in the non-reactive 3,4-epoxide that is converted to a dihydrodiol and 2,3- and 3,4-dichlorophenol.