Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-01-19 to 2005-03-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD TG-428 and in accordance with the principles of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Biphenyl, non radiolabeled 99.8%, biphenyl-14C > 99%
- Molecular formula (if other than submission substance):not applicable
- Molecular weight (if other than submission substance): not applicable
- Smiles notation (if other than submission substance): not applicable
- InChl (if other than submission substance): not applicable
- Structural formula attached as image file (if other than submission substance): not applicable
- Substance type: no data
- Physical state: white solid
- Analytical purity: > 99%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 115 F 9247 (14C) or AE-015 (non labelled)
- Expiration date of the lot/batch: no data
- Radiochemical purity (if radiolabelling): Biphenyl-14C with a purity > 99%
- Specific activity (if radiolabelling): 7.6 mCi/mmoL
- Locations of the label (if radiolabelling): uniformly labelled in both phenyl rings
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: The test substance appeared to be stable under the conditions of the study; no evidence of instability was observed.
- Storage condition of test material: no data
- Other: Origin of non-radiolabelled Biphenyl: Solutia Inc. (Anniston, Alabama, USA)
- Origin of radiolabelled Biphenyl-C14: Sigma Chemical Company (St. Louis Missuri, USA)
Radiolabelling:
yes
Remarks:
Biphenyl C14

Test animals

Species:
human
Strain:
other: Caucasian
Sex:
female
Details on test animals and environmental conditions:
skin samples from abdomen

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: isopropyl myristate
Duration of exposure:
For determining permeability coefficient - observation until 48 h after application
For determining absorption rate - observation until 10 and 60 minutes after application
Doses:
For determining permeability coefficient - 100 µL/cm2 (using a solution of 100 mg biphenyl/mL)
For determining absorption rate - 10 µL/cm2 (using a solution of 100 mg biphenyl/mL)

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Percutaneous absorptionopen allclose all
Dose:
approximately 100 mg/mL, 10 µL/cm2
Parameter:
percentage
Absorption:
0.02 %
Remarks on result:
other: 10 min
Remarks:
Short-term penetration rate = 258.3 µg equiv/cm2/h.
Dose:
approximately 100 mg/mL, 10 µL/cm2
Parameter:
percentage
Absorption:
0.14 %
Remarks on result:
other: 60 min
Remarks:
Short-term penetration rate = 59.1 µg equiv/cm2/h
Dose:
approximately 100 mg/mL, 100 µL/cm2
Parameter:
percentage
Absorption:
3.28 %
Remarks on result:
other: 48 h
Remarks:
Penetration rate at steady state = 6.14 µg equiv/cm2/h. Permeability coefficient = 6.12E-05 cm/h.

Any other information on results incl. tables

Short-term exposure experiments

Following a 10-min exposure to a finite application of biphenyl, a total of 0.60 µg equivalents of biphenyl was detected in the receptor fluid, with 28.1 µg equivalents in the skin. Based on the amount of biphenyl in the receptor fluid and skin, an exposure area of 0.64 cm2 and an exposure time of 10 minutes (0.17 hours), the short-term penetration rate was calculated to be 258.3 µg equiv/cm2/h.

Following a 60-min exposure to a finite application of biphenyl, a total of 1.32 µg equivalents of biphenyl was detected in the receptor fluid and 36.5 µg equivalents in the skin. Based on the amount of biphenyl in the receptor fluid and skin, an exposure area of 0.64 cm2 and an exposure time of one hour, the short-term penetration rate was calculated to be 59.1 µg equiv/cm2/h.

Recovery of the applied radioactive dose was 116.2%.

Permeability coefficient experiment

Based on the slope at steady-state (6.14 µg equiv/cm2/h) and the concentration of the applied dose of biphenyl (100,263 µg/cm3), the permeability coefficient (Kp) was calculated to be 6.12E-05 cm/h. 3.28% of the applied dose was recovered in the receptor fluid.

Recovery of the applied radioactive dose was 94.6%.

Applicant's summary and conclusion

Conclusions:
In this study dermal absorption of biphenyl was investigated in two experiments with human skin samples. In the first experiment, penetration was observed until 48 h after application of 100 µL/cm2 of a 100 mg/µL solution. In the second experiment, penetration was observed until 10 or 60 min after application of 10 µL/cm2 of a 100 mg/µL solution. Based on the first experiment, 3.28% absorption was observed after 48 h and the permeability coefficient was determined to be 6.12E-05 cm/h. In the second experiment, only 0.02 and 0.14% absorption was observed after 10 and 60 min, respectively.