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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Radiolabelling:
yes
Remarks:
[methyl-14C]-Ziram

Test animals

Species:
human
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Duration of exposure:
6h
Doses:
1.55, 643 mg/mL
No. of animals per group:
4-6 diffusion cells per dose
Control animals:
no
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Full-thickness human skin samples (3 abdomen) were obtained post-mortem from two females and one male aged 24 to 64 years old.
- Thickness of skin (in mm): 200-400 µm
- Membrane integrity check: Yes

PRINCIPLES OF ASSAY
- Receptor fluid: 0.01 M phosphate-buffered saline, supplemented with 5% w/v bovine serum albumin, adjusted to pH 7.4 was used as the receptor fluid for the barrier integrity assessment and Ziram permeability assessment.

- Specific activity of test substance: 11.3 MBq/mg (= 305.4 µCi/mg)
- Volume applied: 6.4 µl of each preparation (per 0.64 cm²)
- Sampling time: Receptor fluid: in hourly fractions for the duration of the experiment (24 h).
Tape strips, remaining receptor fluid and washings: at study termination (24 h).

Results and discussion

Absorption in different matrices:
see Table 6_2-1
Total recovery:
see Table 6_2-1

Any other information on results incl. tables

Table A6_2-1       Table for in vitro percutaneous absorption study in human skin
(mean of 4-6 values)

 

Distribution of Radioactivity (% Applied Dose)

Samples

1.55 mg/mL

643 mg/mL

1.         Receptor fluid (0-24 h)

0.38

0.02

2.         Receptor fluid at termination

0.01

nd

3.         Skin

nd

nd

4.         Receptor chamber

nd

nd

5.         Tape (stratum corneum)

1.84

0.04

6.         Total absorbed (1+2+3+4+5)

2.23

0.06

7.         Skin swab (after 6 h)

87.82

93.95

8.         Tape (surface)

1.49

0.11

9.         Donor chamber

0.21

nd

10.      Total non-absorbed (7+8+9)

89.52

94.06

11.      Total recovery (6+10)

91.75

94.12

Applicant's summary and conclusion