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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:
yes

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. (Raleigh, NC)
- Age at study initiation: 81 to 87 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:
other:
Vehicle:
ethanol
Duration of exposure:
72 h
Doses:
- Actual doses: 25 and 400 mg/kg bw
- Dose volume: 200 and 100 µL of 25 and 400 mg/kg bw respectively
No. of animals per group:
Four
Control animals:
no
Details on study design:
DOSE FORMULATION: 16 to 18 µCi radiolabel, an appropriate amount of unlabelled LDEA and 95% ethanol for a total volume of about 200 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: Dose site skin was excised and thoroughly rinsed with ethanol, then gently wiped with cotton gauzes soaked with soapy water.



SAMPLE COLLECTION: 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:
- Absorption was relatively slow, and only about 21 to 26% of the dose penetrated the skin in 72 hr and 3 to 5% remained associated with the dose site.
- No significant differences were observed between doses in the absorption and elimination of LDEA when calculated on a percentage of dose basis. (For details see Table 1 in the attached document).
Total recovery:
- Total recovery: 95 and 92% recovery was observed at 25 and 400 mg/kg bw respectively
Percutaneous absorptionopen allclose all
Dose:
25 mg/kg bw
Parameter:
percentage
Absorption:
ca. 26.3 %
Remarks on result:
other: 72 hours
Remarks:
In 25 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male rats
Dose:
400 mg/kg bw
Parameter:
percentage
Absorption:
ca. 29.2 %
Remarks on result:
other: 72 hours
Remarks:
In 400 mg/kg dose group, disposition of radioactivity after dermal application of radiolabelled LDEA to male rats
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

TBRs (tissue to blood ratio) were higher in liver (30-40) and kidney (ca.20) than adipose tissue (6-7) and non-dose site skin (ca.2).

Results of jugular vein-cannulated rats, dermally dosed at 100 mg/kgbw of LDEA:

- Only LDEA and the half-acid amide metabolites were detected in plasma, and their levels were near maximal at about 24 h after dosing, with no marked changes in the profiles thereafter.

- Most of the circulating LDEA equivalents were comprised of the two metabolites, with about 15% present as LDEA. (See Figure 1 in the attached document).

Applicant's summary and conclusion

Conclusions:
The study indicates that the dermal application of lauramide diethanolamine in rats resulted in moderate (25-30%) absorption.
Executive summary:

A dermal absorption study was conducted to evaluate the absorption of the radiolabelled (14C) lauramide diethanolamine (LDEA) in the Fischer 344 rats. 25 (200 µL) and 400 mg/kg bw (100 µL) of LDEA were 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, feces, dermal rinse solutions and digested skin samples (in 2N ethanolic sodium hydroxide) were collected and analysed for radiochemical content. Absorption was relatively slow, and only about 25 to 30% of the dose penetrated the skin in 72 hr and 3 to 5% remained associated with the dose site. No significant differences were observed between doses in the absorption and elimination of LDEA when calculated on a percentage of dose basis.