resorcinol; 1,3-benzenediol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD/GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Version / remarks:

; OECD Environmental Health and Safety Publications Series on Testing and Assessment No. 28. Guidance Document for the Conduct of Skin Absorption Studies (2004); Basic Criteria for the In Vitro Assessment of Percutaneous Absorption of Cosmetic Ingredients

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Resorcinol

EC Number:

203-585-2

EC Name:

Resorcinol

Cas Number:

108-46-3

Molecular formula:

C6H6O2

IUPAC Name:

resorcinol

Radiolabelling:

yes

Remarks:

[U-14C]-Resorcinol

Test animals

Species:

other: human split-thickness skin membranes

Administration / exposure

Duration of exposure:

0.5 hours then wash, samples taken at 24 hrs post-exposure.

Doses:

Actual Resorcinol concentration in formulation (% w/w): 2.55 (Oxidative); 2.52 (Non Oxidative).
Actual Resorcinol concentration in Test Preparation (% w/w): 1.26 (Oxidative); 1.27 (Non Oxidative).
Actual application rate of Test Preparation (mg/m3): 21.08 (Oxidative); 20.07 (Non Oxidative).

Details on study design:

The study was conducted according to the OECD principles of Good Laboratory Practice and was performed following the SCCNFP, COLIPA and draft OECD guideline for skin penetration studies and the OECD guidance document.

Results and discussion

Total recovery:

Absorption Study – Oxidative Test Preparation
The total recovery, dislodgeable dose, unabsorbed dose, absorbed dose and dermal delivery were 252.02, 248.92, 250.97, 0.84 and 1.04 μg
equiv./cm2, respectively.

Absorption Study – Non Oxidative Test Preparation
The total recovery, dislodgeable dose, unabsorbed dose, absorbed dose and dermal delivery were 249.57, 242.65, 246.62, 2.10 and 2.95 μg
equiv./cm2, respectively.

Percutaneous absorption

Percutaneous absorption 1

Dose:

1.26%

Parameter:

percentage

Absorption:

0.32 %

Remarks on result:

other: 24 hours

Remarks:

oxidative

Percutaneous absorption 2

Dose:

1.27%

Parameter:

percentage

Absorption:

0.82 %

Remarks on result:

other: 24 hours

Remarks:

non-oxidative

Any other information on results incl. tables

Absorption Study – Oxidative Test Preparation

A total of 10 samples of human skin obtained from 5 different donors were dosed topically with [14C]-Resorcinol in the oxidative test preparation of a hair dye formulation (1.25%, w/w). Cells 6, 8, and 13 were rejected from the mean and standard deviation (SD) values due to low mass balance

(outwith 100 ± 10%). The dosing regime for the cells meant that on the first dosing occasion Cell 13 was the last of the cells to be dosed. On the s

econd dosing occasion Cells 6 and 8 were the last two of the cells to be dosed. Bubbles were noted in the pipette tip at the time of dosing these cells. Therefore, the following results are provided as mean values (n = 7).

The mean total recovery was 98.56% of the applied dose at 24 h post dose. At the end of the 0.5 h exposure period, 96.98% of the applied dose was removed during the washing process (95.35% in the 0.5 h skin wash, 1.38 % in the 0.5 h tissue swab and 0.25% in the pipette tips).

At 24 h post dose, ie after a 23.5 h monitoring period, 0.01% of the applied dose was removed from the skin in the 24 h tissue swab. The cell wash

contained 0.37% of the applied dose. Therefore at 24 h post dose, the dislodgeable dose was 97.35% of the applied dose. The total unabsorbed dose was 98.16% of the applied dose. This consisted of the dislodgeable dose and the radioactivity associated with the stratum corneum (0.79%) and unexposed skin (0.02%). Those amounts retained by the stratum corneum and unexposed skin at 24 h are not considered to be dermally absorbed and thus do not contribute to the systemic dose. The absorbed dose (0.32%) was made up from the receptor fluid (0.32%) and the receptor rinse (<0.01%). Dermal delivery (0.40%) was made up from the absorbed dose and exposed skin (0.08%).

The total recovery, dislodgeable dose, unabsorbed dose, absorbed dose and dermal delivery were 252.02, 248.92, 250.97, 0.84 and 1.04 μg

equiv./cm2, respectively.

The lag time and steady state flux could not be accurately determined since the test preparation was removed from the skin surface at 30 min post

dose.

The data shows that [14C]-Resorcinol in oxidative test preparation was effectively removed from the skin surface by the washing procedure

employed.

Absorption Study – Non Oxidative Test Preparation

A total of 12 samples of human skin obtained from 4 different donors were dosed topically with of [14C]-Resorcinol in the non oxidative test

preparation after the addition of water (1.25% w/w). None of the cells were rejected. The following results are provided as mean values (n = 12).

The mean total recovery was 97.44% of the applied dose at 24 h post dose.

At the end of the 0.5 h exposure period, 94.05% of the applied dose was removed during the washing procedure (91.58% in the 0.5 h skin wash, 2.22% in the 0.5 h tissue swab and 0.25% in the pipette tips).

At 24 h post dose, ie after a 23.5 h monitoring period, 0.12% of the applied dose was removed from the skin in the 24 h tissue swab. The cell wash

contained 0.56% of the applied dose. Therefore at 24 h post dose, the dislodgeable dose was 94.73% of the applied dose. The total unabsorbed dose was 96.29% of the applied dose. This consisted of the dislodgeable dose and the radioactivity associated with the stratum corneum (1.50%) and unexposed skin (0.06%). The absorbed dose (0.82%) was made up from the receptor fluid (0.81%) and the receptor rinse (<0.01%). Dermal delivery (1.16%) was made up from the absorbed dose and exposed skin (0.33%).

The total recovery, dislodgeable dose, unabsorbed dose, absorbed dose and dermal delivery were 249.57, 242.65, 246.62, 2.10 and 2.95 μg

equiv./cm2, respectively.

The lag time and steady state flux could not be accurately determined since the test preparation was removed from the skin surface at 30 min post

dose.

The data shows that [14C]-Resorcinol in non oxidative test preparation was effectivelyremoved from the skin surface by the washing procedure

employed.

A summary of the mean results is provided in the table below.

Formulation/Test Preparation	Oxidative	Non Oxidative
Target Resorcinol Concentration in Formulation (%, w/w)	2.50	2.50
Actual Resorcinol Concentration in Formulation (%, w/w)	2.55	2.52
Target Resorcinol Concentration in Test Preparation (%, w/w)	1.25	1.25
Actual Resorcinol Concentration in Test Preparation (%, w/w)	1.26	1.27
Target application rate of Test Preparation (mg/m^2)	20.00	20.00
Actual application rate of Test Preparation (mg/m^2)	21.08	20.07
Resorcinol (% Applied Dose)	Mean ± SD
Dislodgeable Dose	97.35 ± 5.47	94.73 ± 1.97
Unabsorbed Dose *	98.16 ± 5.19	96.29 ± 1.58
Absorbed Dose **	0.32 ± 0.14	0.82  ± 0.66
Dermal Delivery ***	0.40 ± 0.18	1.16 ± 0.88
Mass Balance	98.56 ± 5.10	97.44 ± 1.47
Resorcinol ( µg equiv/cm2)	Mean ± SD
Dislodgeable Dose	248.92 ± 19.87	242.65 ± 7.16
Unabsorbed Dose *	250.97 ± 19.59	246.62 ± 5.90
Absorbed Dose **	0.84 ± 0.39	2.10 ± 1.67
Dermal Delivery ***	1.04 ± 0.51	2.95 ± 2.22
Mass Balance	252.02 ± 19.69	249.57 ± 5.12

*           Unabsorbed dose = dislodgeable dose + stratum corneum + unexposed skin

**          Absorbed dose = receptor fluid + receptor rinse

***        Dermal Delivery = exposed skin (except stratum corneum) + absorbed dose

Applicant's summary and conclusion

Conclusions:

In conclusion, [14C]-Resorcinol in oxidative and non oxidative test preparations was applied topically to human skin in vitro. Under the present
experimental conditions, for [14C]-Resorcinol in the oxidative test preparation, most of the applied dose was removed at 30 min post dose (96.98%
of the applied dose). At 24 h post dose, a further 0.37% was removed; therefore, the dislodgeable dose was 97.35% of the applied dose. At 24 h post
dose, the absorbed dose and dermal delivery were 0.32% (0.84 μg equiv/cm2) and 0.40% (1.04 μg equiv/cm2) of the applied dose, respectively.
Under the present experimental conditions, for [14C]-Resorcinol in the non oxidative test preparation, most of the applied dose was removed at 30
min post dose (94.05% of the applied dose). At 24 h post dose, a further 0.68% was removed; therefore, the dislodgeable dose was 94.73% of the
applied dose. At 24 h post dose, the absorbed dose and dermal delivery were 0.82% (2.10 μg equiv/cm2) and 1.16% (2.95 μg equiv/cm2) of the
applied dose, respectively. The dermal absorption figure to be taken into consideration for the calculation of the margin of safety is 1.04 μg
equiv./cm2 for the oxidative test preparation and 2.95 μg equiv./cm2 for the non oxidative test preparation.