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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: study in limited number of placentas, results are indicative for transfer of test substance accross the placenta

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Type of study / information:
This study was an attempt to construct data needed to develop quantitative structure–activity relationship (QSAR) models that are able to predict placental transfer of new compounds. Test substance was chosen as a model compound.
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In this test with ex vivo human placental perfusion, test substance was chosen as a model compound to develop quantitative structure–activity relationship (QSAR) models for human placental transfer. The total concentration in maternal perfusion media from the beginning of the perfusions was 200 μM test substance. Samples (0.5 mL) were collected from the maternal and fetal perfusion medium before and 2, 5, 10, 15, 30, 45, 60, 90, 120, and 150 min Test substance, was measured by liquid scintillation counting and a calibration curve was included in each test round.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No data given.

Results and discussion

Any other information on results incl. tables

Data from the Individual Perfusion

Parameter

Test substance

13

14A

14B

15

16

Volume loss (M, mL)

6.8

5.3

–16.1

–3.7

–2.6

Volume loss (M, ml)

6.8

2.8

12.2

9.2

10.0

Flow (fetal, mL/2min)

6.8

7.1

7.0

7.1

7.0

Time (birth to lab, min)

29

35

35

30

31

Preperfusion (min)

38

26

19

40

60

Maternal age (yr)

39

37

37

35

26

Placenta weight (g)

730

987

987

700

888

Cotyledon weight (g)

28

12

14

25

15

Total perfused (g)

79

63

80

75

65

Cesarean section

Y

Y

Y

Y

Y

Gestation age (wk + days)

38 + 5

38 + 5

37 + 1

Smoker

N

N

N

N

N

Medicine

Y

Y

Y

N

Y

Test substance (200 μM) rapidly crossed from maternal to fetal circulation. However, a more restricted passage was found in the beginning of the perfusion. The indicative permeability coefficient of test substance was 0.6/h. The FM ratio was 0.91 ± 0.04 after 150 min of perfusion (n = 5). The mass balance of test substance in perfusion media and tissue after end perfusion was 80.4 ± 8.4% when calculated in relation to added radioactivity. During perfusion, 11.4 ± 2.2% of the added [14C] test substance accumulated in the tissue and approximately 3% was bound to the perfusion system.

Applicant's summary and conclusion

Conclusions:
The initial transfer rate of test substance was limited in the first part of the perfusion, but reached the steady-state level by the end of perfusion.
Executive summary:

Test substance was chosen as a model compound to develop quantitative structure–activity relationship (QSAR) models for human placental. The total concentration in maternal perfusion media from the beginning of the perfusions was 200 μM test substance. Samples (0.5 mL) were collected from the maternal and fetal perfusion medium before and 2, 5, 10, 15, 30, 45, 60, 90, 120, and 150 min. Test substance, was measured by liquid scintillation counting and a calibration curve was included in each test round.

The initial transfer rate of test substance was limited in the first part of the perfusion, but reached the steady-state level by the end of perfusion.