Potassium hexadecyl hydrogen phosphate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987-07-20 until 1987-07-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No OECD guideline available at the time the study was performed. Nevertheless the study is similar (with deviations) to OECD guideline 428, scientifically acceptable with some reporting deficiences

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Version / remarks:

13 April 2004

Deviations:

yes

Remarks:

deviations in absorption period, dose applied lower than 10 µL/cm², only one concentration applied.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium hexadecyl hydrogen phosphate

EC Number:

242-768-1

EC Name:

Potassium hexadecyl hydrogen phosphate

Cas Number:

19035-79-1

Molecular formula:

C16H35O4P.K

IUPAC Name:

potassium hexadecyl hydrogen phosphate

Test material form:

other: solution

Radiolabelling:

yes

Test animals

Species:

other: In this in vitro study, skin from naked rats and pigs was used.

Strain:

not specified

Sex:

not specified

Administration / exposure

Type of coverage:

not specified

Vehicle:

ethanol

Remarks:

30 %

Duration of exposure:

1, 6, 16 hours

Doses:

6 µL/cm² equivalent to 300 µg active substance / cm² (the test substance was formulated to yield a concentration of 5% in ethanol (30%)).

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: skin from naked rats and pigs
- Preparative technique:
Active substance prepared 1-5 µCi/ 5 cm² skin site.
Excision of the skin – the skin was separated from fresh operation material. The coonective and adipose tissue is carefully removed and then the skin is separated into round flaps of ca. 20 cm². Every piece was cleaned under floating water, and thereafter is either used directly for the experiment or stored in aluminium foil at -20°C.
Preparation of the excised skin – the skin specimen were marked with areas of 5 cm². 30 µL of the test substance were applied regularly with micropipette on the marked areas. The skin specimen were clamped into the penetration chambers. The lower part of the prepared skin was in constant contact with physiological salt solution, which was slightly moved by a magnetic stirrer throughout the whole experiment (1, 6, 16 hours).

PRINCIPLES OF ASSAY
- Diffusion cell: yes
- Receptor fluid: 0.9 % (w/v) NaCl (continuously stirred)
- Static system: yes
- Test temperature: 32°C
- Occlusion: not specified
- Other: The measurement of activity was carried out with a Packard liquid scintillation spectometer

Results and discussion

Absorption in different matrices:

Most of the radioactivity could be washed off. Minor amounts of radioactivity could be recovered from stratum corneum, epidermis, dermis and receptor fluid. Mean levels of expressed as µg/cm² are presented in a table below in "any othe information on results"

Total recovery:

- Total recovery: naked rat skin or pig skin - 300 µg/cm²
Most of the radioactivity could be washed-off from stratum corneum.

Percutaneous absorption

Key result

Dose:

6 µL/cm²

Parameter:

percentage

Absorption:

> 5.2 - < 9 %

Remarks on result:

other: 1 - 16 hours

Remarks:

mean penetration percent in naked rat and pig skin

Any other information on results incl. tables

		Naked rat skin
µg/cm^2in		Contact time
	1h	6h	16h
skin wipe	261.98	235.37	181.14
Horny layer	22.44	37.37	99.25
Remaining skin tissue layers	15.58	23.85	12.44
Chamber liquid	--	3.41	7.17
Total recovery	300	300	300
Systemic available[1]	15.6	27.3	19.61
Systemic available[2](%)	5.2	9.0	6.5
		Pig skin
skin wipe	269.13	262.52	218.19
Horny layer	13.93	13.97	56.02
Remaining skin tissue layers	16.94	20.34	19.96
Chamber liquid	--	3.17	5.83
Total recovery	300	300	300
Systemic available	16.94	23.51	25.79
Systemic available (%)	5.6	7.9	8.6

 

[1]Amount in skin (without horny layer) and receptor fluid

[2]Calculated based on applied active substance (300 µg/cm²)

Applicant's summary and conclusion

Conclusions:

The test substance (14C-Amphisol) penetrates into skin. Overall, mean penetration was between 5.2 % and 9.0 %. Most of the radioactivity could be washed-off from stratum corneum.

Executive summary:

The in-vitro percutaneous penetration of the test substance was determined using skin from naked rat or pig (thickness not indicated). The penetration was investigated in a static system. The test substance was formulated to yield a concentration of 5% in ethanol (30%). The formulations were applied at dose levels of 6 µL per cm2 (equivalent to 300 µg per cm²) at a temperature of 32°C. Occlusion conditions not specified. Skin integrity testing if performed was not reported.

The penetration of the test substance was determined over 1, 6, and 16 h. After respective contact duration, the skin was wiped with cotton wool, the horny layer was removed by tape stripping. The total radioactivity was determined in all samples (skin wipe, tape strips, remaining skin, receptor fluid, chamber) collected by means of liquid scintillation counting.

Most of the radioactivity could be washed off. Minor amounts of radioactivity could be recovered from stratum corneum, epidermis, dermis and receptor fluid. Based on the radioactivity found in remaining skin and receptor fluid the amount of the test substance absorbed represented between 5.2 – 9.0 %. This corresponds to 15.6 – 27.3 µg test substance equivalents/cm2. Exposure time and type of skin showed no real influence on penetration rate.