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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study, meets generally accepted scientific principles, acceptable for assessment.
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 427 (Skin Absorption: In Vivo Method)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable

GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lauramide diethanolamine (LDEA)
- Radiochemical purity (if radiolabelling): 96 to 97%
- Specific activity (if radiolabelling): 841 µCi/mmol
- Locations of the label (if radiolabelling): On the DEA moiety
- Other: Identity confirmed by mass spectrometry and proton NMR

Radiolabelling:
no

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Inc. (Raleigh, NC)
- Age at study initiation: 72 to 75 d
- Housing: Individual glass metabolism chambers, which allowed separate collection of carbon dioxide, urine, and feces.
- Individual metabolism cages: Yes
- Diet: Purina Rodent Chow (no. 5002), ad libitum
- Water: Ad libitum

Administration / exposure

Type of coverage:
open
Vehicle:
ethanol
Duration of exposure:
72 h
Doses:
- Actual doses: 50, 100, 200 and 800 mg/kg bw
- Dose volume: 50 µL of 50, 100 and 200 mg/kg bw and 30 µL of 800 mg/kg bw

No. of animals per group:
Four
Control animals:
no
Details on study design:
DOSE FORMULATION: 2 to 17 µCi radiolabel, an appropriate amount of unlabelled LDEA and 95 % ethanol for a total volume of about 50 µL per dose


VEHICLE
- Concentration (if solution): 95%


TEST SITE
- Preparation of test site: Application site had been clipped of hair the previous day
- Area of exposure: 1 x 1 inch
- Type of cover / wrap if used: A non-occlusive protective appliance, glued over the dose area with cyanoacrylate adhesive.


SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: No


REMOVAL OF TEST SUBSTANCE: No



SAMPLE COLLECTION: Dose site skin was excised and thoroughly rinsed with ethanol, then gently wiped with cotton gauzes soaked with soapy water. Gauzes and aliquots of urine, dermal rinse solutions, feces, tissues (liver and kidney) and digested skin samples (in 2N ethanolic sodium hydroxide) were collected and analysed for radiochemical content by adding to vials containing scintillation cocktail (Ultima Gold, Packard Instrument Company).


ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
Details on in vitro test system (if applicable):
Not applicable

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
- In 72 hr of exposure, 50 to 70% of the applied doses were absorbed, and there were no statistically significant differences in absorbance across the range of doses.
- The disposition of LDEA in the tissues was approximately the same for the four dose levels. (For details see Table 1 in the attached document).

Total recovery:
- No significant differences in total recovery were observed for the four dose levels (approx. 91, 85, 88 and 85% at 50, 100, 200 and 800 mg/kg bw respectively). For details see Table 1 in the attached document.
Percutaneous absorptionopen allclose all
Dose:
50 mg/kg bw
Parameter:
percentage
Absorption:
ca. 49.1 %
Remarks on result:
other: 72 h
Remarks:
In 50 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male mice
Dose:
100 mg/kg bw
Parameter:
percentage
Absorption:
ca. 66.8 %
Remarks on result:
other: 72 h
Remarks:
In 100 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male mice
Dose:
200 mg/kg bw
Parameter:
percentage
Absorption:
ca. 69.1 %
Remarks on result:
other: 72 h
Remarks:
In 200 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male mice
Dose:
800 mg/kg bw
Parameter:
percentage
Absorption:
ca. 50.2 %
Remarks on result:
other: 72 h
Remarks:
In 800 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male mice
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
The study indicates 50 to 70 % of the applied doses were absorbed, and there were no statistically significant differences in absorption across the range of doses. The disposition of LDEA in the tissues was also similar for the four dose levels.
Executive summary:

A dermal absorption study was conducted to evaluate the absorption of the radiolabelled (14C) lauramide diethanolamine (LDEA) in the B6C3F1 mice. 50 µL of 50, 100 and 200 mg/kg bw and 30 µL of 800 mg/kg bw of LDEA was applied to an area of 1x1 inch previously clipped skin, covered with a non-occlusive patch. After 72 h of exposure, gauzes and aliquots of urine, faeces, dermal rinse solutions and digested skin samples (in 2N ethanolic sodium hydroxide) were collected and analysed for radiochemical content. After 72 h of exposure, 50 to 70 % of the applied doses were absorbed, and there were no statistically significant differences in absorption across the range of doses. The disposition of LDEA in the tissues was also similar across the four dose levels of 50, 100, 200 and 800 mg/kg bw.

The study indicates 50 to 70 % of the applied doses were absorbed, and there were no statistically significant differences in absorption across the range of doses. The disposition of LDEA in the tissues was also similar for the four dose levels.