Poly(oxy-1,2-ethanediyl), α-[2-(dide- cylmethylammonio)ethyl]- .omega.- hydroxy-, propanoate (salt) (Bardap 26)

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary GLP guideline-compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD guideline for the testing of chemicals. Skin absorption: in vitro method. 1999. (Draft)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: COLIPA. Cosmetic ingredients: guidelines for percutaneous absorption/penetration. 1995

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N-Didecyl-N,N-dimethylammonium Chloride

IUPAC Name:

N,N-Didecyl-N,N-dimethylammonium Chloride

Constituent 2

Reference substance name:

DDAC

IUPAC Name:

DDAC

Constituent 3

Reference substance name:

1-Decanaminium, N-decyl-N,N-dimethyl-, chloride

IUPAC Name:

1-Decanaminium, N-decyl-N,N-dimethyl-, chloride

Constituent 4

Reference substance name:

Didecyldimethylammonium chloride

EC Number:

230-525-2

EC Name:

Didecyldimethylammonium chloride

Cas Number:

7173-51-5

Molecular formula:

C22 H48 N.Cl

IUPAC Name:

N-decyl-N,N-dimethyldecan-1-aminium chloride

Constituent 5

Reference substance name:

Bardac 2280

IUPAC Name:

Bardac 2280

Details on test material:

Bardac 2280: Didecyldimethylammonium Chloride in aqueous/alcohol solution (DDAC; CAS RN 7173-51-5), described as a clear, yellow liquid.
The non-radiolabelled substance is hydrolytically and photolytically stable under the conditions of this study and has been shown to be stable in aqueous, alcohol and alcohol/aqueous solutions for extended periods, e.g. at least seven years under standard laboratory conditions

Radiolabelling:

yes

Administration / exposure

Details on in vitro test system (if applicable):

Human dermatomed skin membranes were tested in vitro. Human breast and abdominal full thickness skin samples were obtained from the Plastic Surgery Unit at a UK hospital. The test substance was applied in water at a concentration of 1.85% (target dose level 185 µg/cm²). The tissue culture medium with ca 4% bovine serum albumin maintained with 5% CO2 in O2.

14C-DDAC was applied in aqueous solution at a rate of 10 µl/cm². Receptor fluid was collected hourly from 0h-6h and every other hour from 6-24 h post-dose. At 24 h post-dose, the underside of the skin sample was washed with receptor fluid. The skin surface was washed with 2% soap solution and dried with tissue swabs. The tissue swabs were analysed by combustion. The stratum corneum was removed by successive tape strips. These were extracted with methanol:chloroform (2:1 v/v). The non-dose site skin was collected to determine lateral diffusion through the stratum corneum. The dose site skin was divided into dermis and epidermis by heat separation, then solubilised in Soluene-350. Unabsorbed material was the sum of the skin wash, cell wash, tissue swabs, stratum corneum, cling film and epidermis. Penetration was the sum of receptor rinse and 0-24 h receptor fluid. Dermal delivery was the sum of the dermis and non-dose site skin. Total absorbed material was the sum of dermal delivery and penetration.

Results and discussion

Signs and symptoms of toxicity:

not examined

Remarks:

: in vitro study

Dermal irritation:

not examined

Remarks:

: in vitro study

Absorption in different matrices:

Not investigated

Total recovery:

>99%

Percutaneous absorption

Key result

Time point:

24 h

Dose:

1.85%

Parameter:

percentage

Absorption:

2.92 %

Remarks on result:

other: 1.85% concentration in water

Conversion factor human vs. animal skin:

Not applicable

Any other information on results incl. tables

Less than 0.1% of applied 14C-Didecyldimethylammonium Chloride penetrated the human skin. 2.92% 14C-Didecyldimethylammonium Chloride was absorbed into the skin over 24 hours. 96.25% was not absorbed. Cumulative flux value = 0.11 µg equiv/cm².

Table 1. Mean % recovery after 24 hours

Commodities analysed	Mean recovery  (% of applied dose)
Skin wash	44.45
Cell wash	3.38
Swab	28.14
Cling film	0.05
Stratum corneum	13.75
Epidermis (dose site)	6.49
Dermis (dose site)	2.67
Non-dose site skin	0.18
Receptor fluid	0.06
Receptor rinse	0.00
Cumulative Results
Total penetrated	0.06
Dermal delivery	2.85
Total unabsorbed	96.25
Total absorbed	2.92
Total recovery	99.16

Applicant's summary and conclusion

Conclusions:

Less than 0.1% of the applied 14C-Didecyldimethylammonium Chloride dose penetrated human skin. 2.92% of the applied dose was absorbed into the skin. 96.25% was not absorbed. The cumulative flux value was 0.11 µg equiv/cm².

Executive summary:

¹⁴C-Didecyldimethylammonium Chloride was applied, in an aqueous formulation, to human skin samples using a flow through diffusion cell system. Receptor fluid was collected hourly from 0-6 h and every 2 h from 6-24 h post-dose. After 24 hours the underside of the sample was washed with receptor fluid. The upper side was washed with 2% soap solution and dried with tissue swabs. The stratum corneum was removed with tape strips. The dose site skin was separated into epidermis and dermis, then solubilised.  The non-dose site skin was collected. The amount of radioactivity in each commodity was determined. 

Less than 0.1% of the applied ¹⁴C-Didecyldimethylammonium Chloride dose penetrated human skin. 2.92% of the applied dose was absorbed into the skin. 96.25% was not absorbed. The cumulative flux value was 0.11 µg equiv/cm².