1,1'-(methylenedi-4,1-phenylene)bis(3-butylurea)

Specific investigations: other studies

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

10 other: µM

Remarks:

analytical conc.

Doses / concentrations 2

Dose / conc.:

50 other: µM

Remarks:

analytical conc.

Doses / concentrations 3

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.