3,3'-dichlorobenzidine dihydrochloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

year of publication: 1998

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: secondery sources, data cited from reviews, reliability of original publications not assignable

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicological Profile for 3,3'-Dichlorobenzidine (Update).

Author:

Agency for Toxic Substances and Disease Registry (ATSDR)

Year:

1998

Bibliographic source:

U.S. Department of Health and Human Services; Public Health Service.

Report date:

1998

Reference 2

Reference Type:

publication

Title:

Gesundheitsschädliche Arbeitsstoffe, Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, Loseblattsammlung, 18. Lfg.

Author:

Henschler D

Year:

1992

Bibliographic source:

DFG, Deutsche Forschungsgemeinschaft, VCH Verlag Weinheim

Report date:

1992

Reference 3

Reference Type:

publication

Title:

3,3'-Dichlorbenzidin (3,3'-Dichlor-biphenyl-4,4'-diyldiamin), BUA-Stoffbericht 30.

Author:

Beratergremium für umweltrelevante Altstoffe (BUA)

Year:

1989

Bibliographic source:

VCH Verlag, Weinheim

Report date:

1989

Materials and methods

Principles of method if other than guideline:

investigation of toxicokinetics

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-dichlorobenzidine dihydrochloride

EC Number:

210-323-0

EC Name:

3,3'-dichlorobenzidine dihydrochloride

Cas Number:

612-83-9

Molecular formula:

C12H10Cl2N2.2ClH

IUPAC Name:

3,3'-dichloro-[1,1'-biphenyl]-4,4'-diamine dihydrochloride

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

No quantitative data were located on the absorption of the test substance after oral exposure in humans. The test substance was detected in the urine of workers who were exposed under conditions which favour inhalation. But it cannot be excluded that absorption occurred also via the dermal and/or oral route.
In animals, the test substance is extensively and rapidly absorbed after oral exposure (about 90% of the administered radioactivity were excreted in feces and urine within 72 hours). No data on absorption in animals following inhalation exposure were located.

Details on distribution in tissues:

ATSDR reports that 24 hours after single oral exposure to radioactive labelled test substance the highest levels of radioactivity were found in the liver, followed by the kidney, lung, spleen, heart, pancreas and testes. Four hours after intravenous application of radioactive labelled test substance to rats about 77% of the radioactivity were detected in the intestinum, about 4% in the liver and aboujt 3.4% in the urine, but none in the bile. In contrast, four hours after the intravenous application of the radiolabelled test substance to dogs, 79% of the radioacitivity were detected in the bile, 33% in the intestinum, 4.4% in the liver and about 3% in the urine. Investigating the distribution of the test substance in rats after single i.p. application of 100 mg/kg bw , no test substance was detected in the blood, kidney and liver. Two hours after administration the highest radioactive concentration was measured in the intraperitoneal liquid (about 9%), followed by liver and intestinum (3.9% each), peritoneal fat (2.9%), remaining carcass (2.8) and spleen (1.6%).

Details on excretion:

After oral administration the test substance is mainly excreted in feces (via bile) and urine. In rats a biphasic elimination has been observed. The half lives in plasma were 6 hours and 14 hours for the rapid and slow phase. Elimination of test substance derived radioactivity from liver, kidneys, and lungs was also biphasically with half-lives of 5.8 and 77 hours for the liver, 7.1 and 139 hours for the kidneys and 3.8 and 43.3 hours for the lungs. A half life time of 86 hours and 68 hours has been reported for dogs and rats, respectively. Conjugated metabolites are mainly excreted via bile and feces and unconjugated metabolites mainly via urine. The test item seems to be subject to enterohepatic recirculation.

Metabolite characterisation studies

Details on metabolites:

The test item mainly seems to be metabolised by N-acetylation. In the 24-hour urine of rats unchanged 3,3'-dichlorobenzidine, N-N'-diacetyl-3,3'-dichlorobenzidine, and N-acetyl-3,3'-dichlorobenzidine in a ration of 1:3:10 have been detected after single oral exposure. Additionally, there is indirect evidence for N-oxidation/nitroso-formaton in the rat.

Any other information on results incl. tables

The test substance or its metabolites can probably cross the placenta: After oral exposure of pregnant rats to the test item induction of micronuclei in the liver of the fetuses has been observed. There is no information whether the test item can transfer in breast milk.

From the secondary sources it is often not obvious whether the free base or the dihydrochloride has been applied.