Fatty acids, C16-18 (even numbered), reaction products with tetraethylenepentamine, acetates (salts)

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July/August 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Imidazolium compounds, 2-(C15-17(odd numbered), C17-unsatd. alkyl)-1-[2-(C16-18(even numbered), C18-unsatd. amido)ethyl]-4,5-dihydro-N-methyl, Me sulfates)

IUPAC Name:

Imidazolium compounds, 2-(C15-17(odd numbered), C17-unsatd. alkyl)-1-[2-(C16-18(even numbered), C18-unsatd. amido)ethyl]-4,5-dihydro-N-methyl, Me sulfates)

Radiolabelling:

yes

Remarks:

label on C-atom of N-Methylgroup of the Imidazolinium ring; specific radioactivity: 2.55 mCi/mMol

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Weight at study initiation: 208 g - 252 g
- Housing: individually
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Altromin Alleindiät 1324 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Duration of exposure:

48 h

Doses:

200 mg/animal

No. of animals per group:

5 (0.1% group), 8 (0.5% group)

Control animals:

no

Details on study design:

TEST SITE
- Preparation of test site: clipped
- Area of exposure: 10 cm²
- Time intervals for shavings or clipplings: 24 h before exposure

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: glass capsule fixed with Sicomet 99

REMOVAL OF TEST SUBSTANCE
- Washing procedures and type of cleansing agent: the test item remained on the skin for 48 h until study termination

SAMPLE COLLECTION
- Collection of blood: no
- Collection of urine: 0 - 8 h; 8 - 24 h; 24 - 48 h
- Collection of faeces: 0 - 24 h; 24 - 48 h
- Collection of expired air: 0 - 8 h; 8 - 24 h; 24 - 48 h (3 animals of group 1, 6 animals of group 2)
- Terminal procedure: The animals were killed with CO2, the application site was cut out and the radioactivy determined; teh remaining carcass was homogenised
- Analysis of organs: no
- the metabolism cages were rinsed and the radiactivite determined in the rinsing solution

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
- Limits of detection: 2x background value; ca. 0.2% (urine, faeces)to ca. 6% (carcass) (% of applied radioactivity)

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Time point:

48 h

Concentrate / Dilution:

dilution

Dose:

0.5% dilution, approx. 200 mg solution

Parameter:

percentage

Absorption:

>= 2 - <= 3 %

Percutaneous absorption 2

Time point:

48 h

Concentrate / Dilution:

dilution

Dose:

0.1% dilution, approx. 200 mg solution

Parameter:

percentage

Absorption:

< 0.51 %

Applicant's summary and conclusion

Executive summary:

14C-(N-methyl)-imidazoliniumquat - methosulfate was used for this study. The compound was labelled at the first C-atom in the N-methyl-group of the imidazolinium-ring. 5 and 8 female rats of Wistar-strain (SPF-Cpb) were used respectively as two test groups. The mean body weights amounted to 222 ± 15.4 g (group 1, five animals) and 241 ± 9.72 g (group 2, eight animals). The compound was applied cutaneously as a solution in water. The concentration of 14C-(N-methyl)-imidazoliniumquat-methosulfate was 0.1 % (group 1) and 0.5 % (group 2). The concentrations used in this study were guided by results from skin compatibility studies.
10 cm² of the intact, clipped skin of the rats were exposed for 48 hours to the test substance. Approx. 200 mg of the solutions were applied.  In a 48 hour period <0.51 % (group 1) and 2 - 3 % (group 2) were absorbed through the skin of the rats. An exact value cannot be given because the radioactivity of some samples was below the detection limit.
Additionally the expired air with three rats of the first group and with six rats of the second group was measured for radioactivity. For both groups the radioactivity found was below the detection limit.
The cutaneously absorbed radioactivity was eliminated with the urine and with the feces. The excretion by these two pathways was very low: 0.182% group 1) or 0.149% (group 2) of the applied radioactivity with the urine and 0.330 or 0.919% with the feces.
The radioactivity found in carcass 48 hours after application was below the detection limit in the case of group 1 and below 1.79% for group 2. The radioactivity found in the carcass was, in three of eight animals, below the detection limit. Therefore an exact value cannot be given. The mean value of 1.79% refers to the remaining five animals.
From the results the conclusion can be drawn that the percutaneous absorption of the substance ist quite low. The larger scattering of the single results and the slightly higher value for the percutaneous absorption for the group 2 can probably be ascribed to commencement of skin damage.