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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
other: MAK Collection for Occupational Health and Safety
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no reliability is given as this is a summary entry for the MAK collection

Data source

Reference
Reference Type:
review article or handbook
Title:
1,3-dichlorobenzene - Supplement 2008
Author:
MAK
Year:
2013
Bibliographic source:
The MAK-collection Part I, MAK Value documentation 2013, DFG, Deutsche Forschungsgemeinschaft 2013 Wiley-VCH Verlag GmbH & Co. KGaA

Materials and methods

Principles of method if other than guideline:
MAK Collection for Occupational Health and Safety
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
1,3-dichlorobenzene is hydroxylated in the liver by cytochrome P450-dependent monooxygenases via a reactive epoxide to form a phenolic compound which is eliminated as a glutathione conjugate, glucuronide or sulfate. At least twelve metabolites, for the most part glutathione conjugates and their degradation products, were isolated in the gallbladder of rats after intraperitoneal injection of 1,3-dichlorobenzene. The main metabolites were trans-2,4-dichloro-6-(glutathione-S-yl)cyclohexa-2,4-dien-1-ol and trans-3,5-dichloro-6-(glutathione-S-yl)cyclohexa-2,4-dien-1-ol as well as their resultant cysteine conjugates. Eliminated as further metabolites were 3,5-dichlorophenyl conjugates with glutathione or cysteine and 3,5-dichlorophenyl mercapturic acids and their 2,4-dichlorophenyl isomers, including S-(2,4-dichlorophenyl)cysteine and S-(3,5-dichlorophenyl)cysteine.

Any other information on results incl. tables

Cultivation of liver slices from Sprague-Dawley rats showed that about 70% of the 1,3-dichlorobenzene is metabolized to glutathione and cysteine conjugates and only small quantities, about 3% to 5%, to glucuronides or sulfates. In cultivated human liver slices, on the other hand, about 40% of the substance is found as glucuronide or glutathione conjugates and about 20% as sulfates.

A further study with human liver slices and liver slices from Fischer-344 and Sprague-Dawley rats confirmed that mainly glutathione and cysteine conjugates and in human liver slices noticeably more glucuronides occur than in liver slices from rats.

Applicant's summary and conclusion