Butanamide, 2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[3-oxo-, N,N'-bis(4-chloro-2,5-dimethoxyphenyl and 2,4-xylyl) derivs.

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

year of publication: 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Lack of bioavailability of dichlorobenzidine from diarylide azo pigments: molecular dosimetry for hemoglobin and DNA adducts

Author:

Sagelsdorff P, Haenggi R, Heuberger B, Joppich-Kuhn R, Jung R, Weideli, HW, Joppich M

Year:

1996

Bibliographic source:

Carcinogenesis 17: 507-514

Report date:

1996

Materials and methods

Objective of study:

other: bioavailability of the hypothetical cleavage product 3,3'-dichlorobenzidine (DCB) from the submission substance after oral application

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

investigation of formation of DCB-hemoglobin and DCB-DNA-adducts

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3-oxobutyramide]

EC Number:

225-822-9

EC Name:

2,2'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[N-(2,4-dimethylphenyl)-3-oxobutyramide]

Cas Number:

5102-83-0

Molecular formula:

C36H34Cl2N6O4

IUPAC Name:

2,2'-[(3,3'-dichlorobiphenyl-4,4'-diyl)didiazene-2,1-diyl]bis[N-(2,4-dimethylphenyl)-3-oxobutanamide]

Test material form:

not specified

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

4 weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
0.2% in diet (corresponding to 170 mg/kg bw)

No. of animals per sex per dose / concentration:

6 females

Control animals:

no

Positive control reference chemical:

DCB, application via drinking water

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

- in three rats no DCB or AcDCB-hemoglobin adducts were detectable (limit of detection: 0.1 ng/g hemoglobin)
- in the remaining three animals adduct levels slightly higher than the individual detection limits for DCB and AcDCB of 0.1 ng/g hemoblobin were detected (total adduct levels < 0.24 - 0.41 ng/g hemoglobin)
- in 2/3 rats liver DNA-adducts slightly above the limit of detection (0.08 ng/g DNA) were detected (0.30 and 0.15 ng adducts/g DNA)

Any other information on results incl. tables

- no signs of toxicity were noticed during the 4 week treatment period

- food consumption and body weight development were similar in treated and in control animals

- the authors concluded that the DCB-adducts were due to the contamination of the test item with the monoazo compound

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: the test item is not metabolically splitted into DCB and no DCB becomes bioavailable after repeated oral application
The results indicate that the test item is not metabolically splitted into DCB and that no DCB becomes bioavailable after repeated oral application of the test item. Detection of minimal DCB-hemoglobin adducts in 3/6 rats and minimal DCB-DNA-adducts in the liver of 2/3 rats is probably due to the contamination of the test item with the monoazo compound.

Executive summary:

Female Wistar rats were treated for 4 weeks with 0.2% C.I. Pigment Yellow 13 in the diet. At the end of the exposure period. The hypothetical release of 3,3'-dichlorobenzidine was investigated by analysis of DCB-hemoglobin adducts and DCB-DNA-adduct levels in the liver. Minimal DCB-hemoglobin adducts in 3/6 rats and minimal DCB-DNA-adducts in the liver of 2/3 rats are probably due to the contamination of the test item with the monoazo compound. The results indicate that no DCB is bioavailable after oral ingestion of the test item.