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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-04-17 to 2007-06-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
No guideline is available for this test. Test procedure: The objective of this study is to incubate a test item with primary human hepatocytes to investigate the potential formation of critical metabolites/structures. Hepatocytes provide cellular integrity with respect to enzyme architecture and contain the full complement of drug metabolizing enzymes. Thus, the applied suspension cultures of human hepatocytes (male/female) represent a suitable tool for metabolic profile studies and are recommended for this purpose by the FDA concept paper (September 2006).
GLP compliance:
yes
Type of method:
in vitro
Endpoint addressed:
basic toxicokinetics

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
416-600-4
EC Name:
-
Cas Number:
77703-56-1
Molecular formula:
C23H32N4O2
IUPAC Name:
3-butyl-1-[4-({4-[(butylcarbamoyl)amino]phenyl}methyl)phenyl]urea
Specific details on test material used for the study:
Analytical purity: > 99.4 %
Lot/batch No.: HAT-ISO 05-12-06

Test animals

Species:
other: in vitro test
Strain:
other: in vitro test

Administration / exposure

Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
1, 2 and 4 hours
Frequency of treatment:
Not applicable
Post exposure period:
Not applicable
Doses / concentrationsopen allclose all
Dose / conc.:
10 other: µM
Remarks:
analytical conc.
Dose / conc.:
50 other: µM
Remarks:
analytical conc.
Dose / conc.:
1 000 other: µM
Remarks:
analytical conc.
No. of animals per sex per dose:
Not applicable
Control animals:
other: not applicable

Results and discussion

Details on results:
The test item samples were analysed to assess potential formation of 4,4’-diaminodiphenylmethane (4,4’-MDA), following metabolisation of HAT-ISO by human hepatocytes.
Viability of the cells was 90%.
Formation of 6ß-hydroxytestosterone in the positive control proved the functionality of the hepatocytes.
In none of the analyzed HAT-ISO treatment and control samples was 4,4'-MDA detected.
The limit of detection was 10 ng/mL or 10 ppm.

Applicant's summary and conclusion

Conclusions:
The test item and negative control samples were analysed to assess potential formation of 4,4’-diaminodiphenylmethane (4,4’-MDA), following metabolisation of HAT-ISO by human hepatocytes.
In none of the analysed HAT-ISO treatment and control samples was 4,4’-MDA detected.
The limit of detection was 10 ng/mL or 10 ppm.
Executive summary:

The objective of this study was to incubate the test item HAT-ISO with primary human hepatocytes to investigate the potential formation of critical metabolites/structures.

Hepatocytes provide cellular integrity with respect to enzyme architecture and contain the full complement of drug metabolizing enzymes.

The test item and negative control samples were analysed to assess potential formation of 4,4’- diaminodiphenylmethane (4,4’-MDA), following metabolisation of HAT-ISO by human hepatocytes.

In none of the analysed HAT-ISO treatment and control samples was 4,4’-MDA detected.

The limit of detection was 10 ng/mL or 10 ppm.