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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1d. Test procedure in accordance with generally accepted sceintific standards and described in sufficient detail.

Data source

Reference
Reference Type:
publication
Title:
3,Q-Benzpyrene and N-Methylaniline Metabolizing Enzymes in the Immature Human Foetus and Placenta
Author:
Pelkonen O., Arvela P. and Karki N.T.
Year:
1971
Bibliographic source:
Acta pharmacol. et toxicol. 1971, 30, 385-395.

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline required
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
human

Administration / exposure

Route of administration:
other: Not applicable: in vitro study
Vehicle:
not specified
Duration and frequency of treatment / exposure:
Not applicable: in vitro study
Doses / concentrations
Remarks:
Doses / Concentrations:
Not relevant.
No. of animals per sex per dose:
Not applicable: in vitro study
Control animals:
other: Not applicable: in vitro study

Results and discussion

Main ADME resultsopen allclose all
Type:
metabolism
Results:
Metabolizing enzymes were present in liver tissues of all foetuses. The activity was not proportional to foetal age. The requirements for full activity in the foetal liver depended on NADP, glucose-6-phosphate and Mg++ ions.
Type:
metabolism
Results:
Human foetal liver: 0.7 pmol N-methylaniline per gram tissue per hour
Type:
metabolism
Results:
No significant activity in foetal gastrointestinal tract, brain, kidneys, and lungs.
Type:
metabolism
Results:
No significant activity in in placenta tissue except for one (out of five), which showed activity comparable to liver tissue.

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters
Test no.:
#1
Toxicokinetic parameters:
other: Michaelis constant Km for N-methylaniline demethylase: 1.2 X 10-4 M.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Demethylation of N-methylaniline to aniline.

Any other information on results incl. tables

Table 1: Metabolism of N-methylaniline by human fetal liver tissue in (mmol/g/h).

Tissue

Mean

range

Liver

-homogenate

0.61

0.34-0.90

-supernatant

0.50

0.27-0.82

-microsomal fraction

0.46

0.37-069

-soluble fraction

0.02

Stomach

0.01

Small intestine

0.15

Large intestine

0.06

Kidneys

0.16

Lungs

0.01

Brain

0.00

Adrenal gland

0.26

0.07-0.35

Testes

0.00

Placenta

0.08

0.00-0.26

Adult rat liver

3.74

2.77-5.02

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
This study examined demethylation of N-methylaniline in human foetuses and compared to rat livers, activity in liver tissue of the foetuses ranged from 5 to 15 % of the value observed in the rat liver. The Km value obtained, 1.2 X 10-4 M, was of the same order of magnitude as those reported for animal and human liver demethylases.