Amides, C12-18 and C18-unsatd., N,N-bis(hydroxyethyl)

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Lauramide diethanolamine absorption, metabolism and disposition in rats and mice after oral, intravenous and dermal administration

Author:

Mathews JM, deCosta K and Thomas BF

Year:

1996

Bibliographic source:

Drug Metab. Dispos. 24(7):702-710

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(2-hydroxyethyl)dodecanamide

EC Number:

204-393-1

EC Name:

N,N-bis(2-hydroxyethyl)dodecanamide

Cas Number:

120-40-1

Molecular formula:

C16H33NO3

IUPAC Name:

N,N-bis(2-hydroxyethyl)dodecanamide

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:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system 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

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

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 substance in the tissues was similar across the four dose levels.

Total recovery:

Approximately 91, 85, 88 and 85% at 50, 100, 200 and 800 mg/kg bw, respectively.

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

72 h

Dose:

50 mg/kg bw

Parameter:

percentage

Absorption:

ca. 49.1 %

Percutaneous absorption 2

Key result

Time point:

72 h

Dose:

100 mg/kg bw

Parameter:

percentage

Absorption:

ca. 66.8 %

Percutaneous absorption 3

Key result

Time point:

72 h

Dose:

200 mg/kg bw

Parameter:

percentage

Absorption:

ca. 69.1 %

Percutaneous absorption 4

Key result

Time point:

72 h

Dose:

800 mg/kg bw

Parameter:

percentage

Absorption:

ca. 50.2 %

Conversion factor human vs. animal skin:

No data

Applicant's summary and conclusion

Conclusions:

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 substance in the tissues was similar across the four dose levels.

Executive summary:

A study was conducted to evaluate the dermal absorption of (14C) radiolabelled N,N-bis(2-hydroxyethyl)dodecanamide (C12DEA, also known as LDEA) in B6C3F1 mice. Four male mice were exposed to a single dose of 50, 100, 200 or 800 mg/kg bw of the substance placed on a 1x1 inch surface of 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 by liquid scintillation counting. 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 substance in the tissues was similar across the four dose levels (Mathews, 1996).