5-[(2-hydroxyethyl)amino]-o-cresol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997/03/03 to 1997/05/09

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

2005

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Although the study was performed in 1997 before the current OECD or SCCNFP guidelines, it was mostly performed according to the methodology recommended by these guidelines .

GLP compliance:

not specified

Remarks:

in compliance

Test material

Test material information

Constituent 1

Reference substance name:

5-[(2-hydroxyethyl)amino]-o-cresol

EC Number:

259-583-7

EC Name:

5-[(2-hydroxyethyl)amino]-o-cresol

Cas Number:

55302-96-0

Molecular formula:

C9H13NO2

IUPAC Name:

5-[(2-hydroxyethyl)amino]-2-methylphenol

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

test batch CFQ9704 of 5-(2-hydroxyethylamino)-2-methyl [U-14C] phenol (98.7% radiochemical purity)

Radiolabelling:

yes

Test animals

Species:

other: Human

Sex:

female

Administration / exposure

Details on study design:

The objective of the study was to evaluate the in vitro human percutaneous absorption and cutaneous distribution of the coupler 2-METHYL-5- HYDROXYETHYLAMINO-PHENOL (COLIPA A031, IMEXINE OAG) under in-use conditions.
For this purpose, the coupler 2-METHYL-5-HYDROXYETHYLAMINO-PHENOL (COLIPA A031, IMEXINE OAG) was incorporated at ca 3% (w/w) into two typical hair dye formulations containing or not a primary intermediate (p-PHENYLENEDIAMINE). The formulations were applied on the skin surface after mixing (1/1, w/w) with H202 or H2O to give a final concentration of ca 1 .5% (w/w).
The study was performed on human dermatomed skin . This skin model was shown o be prédictive 1 for in vivo resuits in Humans.

Details on in vitro test system (if applicable):

Test Procedure
Skin samples (486 ± 121 μm in thickness) were dermatomed and mounted in 2cm² flow-through diffusion cells, using phosphate-buffered saline as the receptor fluid (flow rate 6 ml/h). Their integrity was checked before application of the formulation by measuring the trans-epidermal water loss. The skin was maintained at 32°C.
The test item (coupler) was tested under three different conditions:

- Imexine OAG + primary intermediate (p-phenylenediamine, PPD) in the presence of developer (hydrogen peroxide, (H2O2): use conditions; 8 diffusion cells used. The hair dye formulation 175303 containing the coupler (unlabelled + [14C] _
2 .84 ± 0.45 %, w/w) associated to a primary intermediate (p-PHENYLENEDIAMINE1 .94 % (w/w)) applied in a 1/1 (w/w) mixture with the developer hydrogen peroxide (final concentration = 1 .38 ± 0 .13 %, w/w), in order to study the penetration of the coupler under usual dyeing conditions.
- Imexine OAG alone in the presence of H2O2: oxidative conditions; 6 diffusion cells used. the hair dye formulation 175302 containing the coupler alone (unlabelled + [14C] 2.99 ± 0 .32 %, w/w) applied in a 1/1 (w/w) mixture with water (final concentration = 1 .44 ± 0 .02 %, w/w), in order to study the penetration of the coupler itself.
- Imexine OAG in the presence of water: non-oxidative conditions; 6 diffusion cells used. The hair dye formulation 175302 containing the coupler alone (unlabelled + [14C] _2.99 ± 0 .32 %, w/w) applied in a 1/1 (w/w) mixture with the developer hydrogen peroxide (final concentration = 1 .53 ± 0 .06 %, w/w), in order to study the penetration of the coupler under oxidative conditions.

For the in use conditions, Imexine OAG was incorporated into a typical hair colouring formulation at 3% (w/w) associated with the primary intermediate PPD at 1.94%, before mixing with developer (1:1, w/w) to yield a final concentration of 1.5% Imexine OAG (w/w). In other conditions, it was incorporated at 3% into the same formulation devoid of primary intermediate before mixing with developer or water (1:1, w/w) to give a similar final concentration of 1.5% Imexine OAG (w/w).
About twenty (20) mg/cm² of each hair dye mixture was applied to the skin surface for about 30 minutes. After this time period, the remaining formulation on the skin surface was removed using a standardized washing procedure, simulating use conditions. Twenty-four (24) hours after application, the percutaneous absorption of 5-(2-hydroxyethylamino)-2-methyl [U-14C] phenol was estimated by measuring its concentration by Liquid Scintillation Counting in the following compartments: skin excess, stratum corneum (isolated by tape strippings), living epidermis + dermis and receptor fluid.

The following analytical controls of the unlabelled and the radiolabelled hair dye formulations and mixtures were performed at each experiment :
• Radiochemical purity of [14C]-2-METHYL-5-HYDROXYETHYL4MINO-PHENOL in the radiolabelled hair dye formulations (HPLC),
• Total concentration of 2-METHYL-5-HYDROXYETHYLAMINO-PHENOL (unlabelled + [14C]) in the radiolabelled hair dye formulations (HPLC),
• Radioactive concentration (expressed as mCi/g) of the hair dye formulations and mixtures (Iiquid scintillation counting).

Analysis of the cutaneous distribution
The following parameters were evaluated :
• Analysis of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-byproducts quantities in the following compartments :
o Skin excess
o Stratum corneum (isolated by tape strippings)
o Epidermis
o Dermis
o Receptor fluid
• Absorbed amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]- by-products: epidermis + dermis + receptor fluid .
• Kinetics of [14C]-2-METHYL-5-HYDROXYETHYLAMLNO-PHENOL and/or [14C]-by-products diffusion in the receptor fluid.
Results are expressed as :
o µg eq/cm² (µg equivalent of 2-METHYL-5-HYDROXYETHYLAMINO-PHENOL/ cm²)
o % of 2-METHYL-5-HYDROXYETHYLAMINO-PHENOL 1 applied dose
Statistical analysis:
Statistical analysis of the results was performed by M . Tolle (Modélisation et Statistique, Direction des Sciences de la Matière, L'Oréal, Aulnay-Sous-Bois) (report MT/Juin97/01) .
The following statistical methods were used :
• Descriptive statistics (means, standard deviations, ...).
• Mixed model variance analysis using skin donor as random factor (repeated measures on this factor) and the hair dye mixtures as fixed factor.
• For the kinetics comparison, mixed model variance analysis using skin donor as random factor (repeated measures on this factor) and the hair dye mixtures and the time as fixed factor, taking into account the hair dye mixture*time interaction.
• The variance analysis was followed by a Tukey test for the comparisons of means.
The significance between the means is evaluated at the risk a = 5 %.

Results and discussion

Signs and symptoms of toxicity:

not examined

Absorption in different matrices:

Under the present experimental conditions, this study showed that:
For the three pair dye mixtures, most of the coupler applied on the skin surface was removed with the washing procedure (i .e ., 95.7 ± 0 .8 %, 94.4 ± 3.8 % and 93 .4 ± 1 .4 % of the applied dose for 175303 [14C] + H2O, 175302 [14C] + H2O and 175302 [14C] + H202, respectively) .
Concerning the skin distribution of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products, no major differences were observed between the three hair dye mixtures:
In the stratum corneum, similar amounts were found for the three hair dyes mixtures :
0.12 ± 0.07 %, of the applied dose for 175303 [14C] + H2020.33 ± corresponding to 0 .20 µgeq/cm²
0 .13 ± 0 .05 % of the applied dose for 175302 [14C] + H2O corresponding to 0.36 ± 0.13 µgeq/cm²
0.24 ± 0 .22 % of the applied dose and 175302 [14C] + H202, corresponding to 0 .72 ± 0.68 µgeq/cm²
Those amounts retained in the stratum corneum 24 hours post-application were not considered to be percutaneously absorbed and thus did not contribute to the systemic dose at this time.
In the epidermis, similar amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINOPHENOL and/or [14C]-by-products were found for the three hair dye mixtures :
0 .52 ± 0.43 % (1 .42 ± 1 .19 µgeq/cm²) for 175303 [14C] + H202
0 .33 ± 0.15 % (0 .94 ± 0.38 µgeq/cm²) for 175302 [14C] + H2O
0 .34 ± 0 .18 % of the applied dose (1 .01 ± 0.49 µgeq/cm²) for 175302 [14C] + H202,
In the dermis, the amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products were Iow and again did not differ significantly for the three hair dye mixtures :
0.02 ± 0 .01 % (0 .05 * 0.03 µgeq/cm²), for 175303 [14C] + H2O2
0.04 ± 0.02% (0 .11 ± 0 .04 µgeq/cm²), for 175302 [14C] + H2O
0.05 ± 0.04 % of the applied dose (0 .15 ± 0 .12 µgeq/cm²), for 175302 [14C] + H2 02
In the receptor fluid, the amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINOPHENOL and/or [14C]-by-products (i.e., penetrated amounts) tended to be lower for
175303 [14C] + H202 and 175302 [14C] + H202 (0.42 ± 0 .26(1 .11 ± 0 .62 µgeq/cm²) and 0.39 ± 0 .12 % (1 .18 ± 0 .34 µgeq/cm²), respectively than for
175302 [14C] + H2O (0.83 ± 0.59 % of the applied dose,2.38 ± 1 .68 µgeq/cm²).
The skin distribution showed that, in presence of developer, the production of high molecular weight products (formed by oxidation and coupling reactions of the coupler with the primary intermediate) tended to decrease the diffusion of the coupler to the dermis and the receptor fluid and therefore its absorption.

Absorbed amounts [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C] by-products (epidermis + dermis + receptor fluid) were not significantly different for the three hair dye mixtures:
- 2.58 ± 1.03 µgeq/cm²) (0 .95 ± 0.39 % of the applied dose) for 175303 [14C] + H202,
- 3.44 ± 1.89 µgeq/cm²) (1 .21 ± 0.68 % of the applied dose) for 175302 [14C] + H2O,
- 2.35 ± 0.79 µgeq/cm²) (0.77 ± 0.29 % of the applied dose) for 175302 [14C] + H202.

Percutaneous absorption

Key result

Dose:

IMEXINE OAG incorporated at 1.5% (final concentration)

Parameter:

amount

Absorption:

ca. 4.56 other: µg/cm²

Remarks on result:

other: maximum absorption in a typical oxidative hair dye formulation

Any other information on results incl. tables

Table of cutaneous distribution of [14C]-2 -METHYL-5 -HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products after applilcation on human dermatomed skin. Results (mean +/- SD) are expressed as µg eq/cm² and % of the applied dose.

Hair dye mixture	175303 [14C] + H2O2 (n=8)	175302   [14C] + H2O (n=6)	175302   [14C] + H2O2 (n=6)
skin excess µg eq/cm² % of the applied dose	262.3 +/- 20.8 95.7 +/- 0.8	270.7 +/- 14.9 94.4 +/- 3.8	286.2 +/- 10.3 93.4 +/- 1.4
stratum corneum (SC)  µg eq/cm² % of the applied dose	0.33 +/- 0.2 0.12 +/- 0.07	0.36 +/- 0.13 0.13 +/- 0.05	0.72 +/- 0.68 0.24 +/- 0.22
Epidermis  µg eq/cm² % of the applied dose	1.42 +/- 1.19 0.52 +/- 0.43	0.94 +/- 0.38 0.33 +/- 0.15	1.01 +/- 0.49 0.34 +/- 0.18
Dermis  µg eq/cm² % of the applied dose	0.05 +/- 0.03 0.02 +/- 0.01	0.11+/- 0.04 0.04 +/- 0.02	0.15 +/- 0.12 0.05 +/- 0.04
Receptor fluid (RF)  µg eq/cm² % of the applied dose	1.11 +/- 0.62 0.42 +/- 0.26	2.38 +/- 1.68 0.83 +/- 0.59	1.18 +/- 0.34 0.39 +/- 0.12
Total recovery  µg eq/cm² % applied dose	2.58 ± 1.03  96.8 +/- 1.2	3.44 ± 1.89      95.7 +/- 3.1	2.35 ± 0.79     94.4 +/- 1.6

Table of absorbed amounts [14C]-2 -METHYL-5 -HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products after application on human dermatomed skin. Results (mean +/- SD) are expressed as µg eq/cm² and % of the applied dose.

HAIR DYE MIXTURE	175303 + H2O2 (n=8)	175302 + H2O (n=6)	175302 + H2O2 (n=6)
Penetration amount µg eq/cm² % of the applied dose	1.11 +/- 0.62 0.42  +/- 0.26	2.38 +/- 1.68 0.83  +/- 0.59	1.18 +/- 0.34 0.39  +/- 0.12
Absorbed amount  µg eq/cm² % of the applied dose	2.58 +/- 1.03 0.95  +/- 0.39	3.44 +/- 1.89 1.21  +/- 0.68	2.35 +/- 0.79 0.77  +/- 0.29

Table of control of the unlabelled and the radiolabelled hair dye formulation and mixtures (mean +/- SD, CV %)

HAIR DYE FORMULATION	175303 [14C] (n=3)	175302 [14C] (n=3)
Total concentration (%) (unlabelled + [14 C]	2.84 +/- 0.45	2.99  +/- 0.32
Radioactive concentration (mCi/g)	1.32 +/- 0.47	1.08 +/- 0.21

HAIR DYE MIXTURES	175303 [14C] + H2O2 (n=3)	175302 [14C] + H2O (n=3)	175302 [14C] + H2O (n=3)
Total concentration (%) (unlabelled + [14 C]	1.38 +/- 0.13	1.44 +/- 0.02	1.53 +/- 0.06
Radioactive concentration (mCi/g)	0.62 +/- 0.12	0.52 +/- 0.06	0.55 +/- 0.09

Skin distribution

The statistical analysis of the results was difficult due to the heterogeneity of the study plan concerning the donor repartition for each hair dye mixture tested (D1, D2 and D4 for 175302 [14 C] + H2O and 175302 [14C] + H202; D3 and D4 for 175303 [14C] + H202) and the number of samples (n = 6, 6 and 8, respectively).

Nevertheless, the following tendencies were noticed. Most of the hair dye mixtures applied on the skin surface were removed with the washing procedure after 30 minutes of application. The amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHÉNOL and/or [14C]-by-products did not differ significantly between the three hair dye mixtures ( 95.7 ± 0.8 %, 94.4 ± 3.8 % and 93.4 ± 1.4 % of the applied dose for 175303 [14C] + H202,175302 [14C] + H2O and 175302 [14C] + H202, respectively) . A slight skin staining was observed in the case of the hair dye mixture containing the coupler + primary intermediate mixed with developer (H202).

In the stratum corneum, similar amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINOPHENOL and/or [14C]-by-products were found for the three hair dye mixtures: 0.12±0 .07%, 0.113±0.05%, and 0 .24±0.22% of the applied dose for 175303 [14C] + H202, 175302 [14C] + H2O and 175302 [14C] + H202, respectively. The result for the latter hair dye mixture seemed to be higher and much more variable due to the higher result obtained in one diffusion cell (cell 3 in experiment 1 ; without this cell, the result decreased to 0.15 ± 0.08 % of the applied dose).

In the epidermis, similar amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products were found for the three hair dye mixtures ; nevertheless, the result obtained for the hair dye mixture containing the coupler + primary intermediate mixed with developer tended to be higher : 0.52 ± 0.43 %, 0.33 ± 0.15 %, and 0.34 ± 0.18 % of the applied dose for 175303 [14C] + H202, 175302 [14C] + H2O and 175302 [14C] + H 202, respectively.

In the dermis, the amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or C]-by-products were low and again similar for the three hair dye mixtures: 0.02 ± 0.01 %, 0.04 ± 0.02 %, and 0.05 ± 0.04 % of the applied dose for 175303[14C] + H2O2, 175302 [14C] + H2O and 175302 [i4C] + H202, respectively . No storage of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products was observed in the dermis.

In the receptor fluid (RF), the amounts of [ 14C]-2-METHYL-5-HYDROXYETHYLAMINOPHENOL and/or [14C]-by-products (i .e., penetrated amounts) were similar for the formulations mixed with developer (0.42 ± 0.26 % and 0.39 ± 0.12 % of the applied dose for 175303 [14C] + H202 and 175302 [14C] + H202 , respectively) and tended to be higher for the formulation mixed with water (0.83 ± 0.59 % of the applied dose for 175302 [14C] + H20).

Given that 2-METHYL-5-HYDROXYETHYLAMINO-PHENOL is a rather hydrophilic (Log P = 0.7), it is interesting to notice that higher amounts of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products were found in the epidermis (more hydrophilic skin layer) and in the receptor fluid than in the stratum corneum (more lipophilic skin layer).

The absorbed amounts (epidermis + dermis + RF) of [ 14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products were not significantly different for the three hair dye mixtures. They represented 0.95 ± 0.39 %, 1.21 ± 0.68 % and 0.77 ± 0.29 % of the applied dose for 175303 [14C] + H202, 175302 [i4C] + H2O and 175302 [14C] + H202, respectively.

Total recoveries of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-byproducts were also similar: 96.8 ± 1.2 %, 95.7 ± 3.1 % and 94.4 ± 1.6 % of the applied dose for 175303 [14C] + H202,175302 [14C] + H2O and 175302 [14C] + H202, respectively.

Cutaneous penetration kinetics

The shape of the kinetics was similar for the three hair dye mixtures. The major part of the transcutaneous penetration of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [14C]-by-products took place during the first 2-3 hours after application, clearly showing the absence of a reservoir effect in the stratum corneum.

But, the kinetics of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [ 14C]-byproducts    diffusion in the receptor fluid tended to be significantly higher 3 hours post-application, for 175302 [14C] + H2O than for 175303 [14 C] + H2O2 and 175302 [14C] + H202.

Comparison of the three hair dye mixtures

The following trend was observed : the diffusion of the coupler through the skin into the receptor fluid and therefore its absorption tended to be higher for 175302 [14C] +H20 than for 175303 [14C] + H202 and 175302 [14C] + H202. In fact, for 175302 [14 C] + H2O, the coupler is alone and no oxidation and coupling reactions occurred, it may be assumed that the amounts of product found mainly corresponded to the coupler itself. For 175303 [14C] + H202 and [14C] + H202, in presence of developer (hydrogen peroxide), the coupler with (and in a lesser extend without) the primary intermediate underwent oxidation and coupling reactions leading to higher molecular weight reaction products having a Iower potential of absorption.

Applicant's summary and conclusion

Conclusions:

The dermal absorption (sum of the amounts measured in the living epidermis, dermis and receptor fluid) of Imexine OAG incorporated at 1.5% (final concentration) in a typical oxidative hair dye formulation was estimated to be 2.58 ± 1.03 μg/cm² (1.49-4.56 μg/cm²) in use conditions. The maximal penetration in non-oxidative conditions was 3.44 ± 1.89 μg/cm² (1.10-5.55 μg/cm²). The maximum absorption in a typical oxidative hair dye formulation was 4.56 μg/cm² (epidermis + dermis + receptor fluid) which corresponds to 1.56% of the applied dose. This figure is used for the calculation of the Margin of Safety. For REACh worker safety, the maximal absorption in non-oxicdative conditions was 5.55 µg/cm² (epidermis + dermis + receptor fluid) which corresponds to 2.05% of the applied dose.

Executive summary:

The objective of the study was to evaluate the in vitro human percutaneous absorption and cutaneous distribution of the coupler 2 -METHYL-5- HYDROXYETHYLAMINO-PHENOL (COUPA A031, IMEXINE OAG) under in-use conditions.

For this purpose, the coupler 2-METHYL-5 -HYDROXYETHYLAMINO-PHENOL (COUPA A031, IMEXINE OAG) was incorporated at ca 3% (wlw) into two typical hair dye formulations containing or not a primary intermediate (p-PHENYLENEDIAMINE). The formulations were applied on the skin surface alter mixing (1/1, w/w) with H202 or H2O to give a final concentration of ca 1 .5% (w/w).

The study was performed on human dermatomed skin samples mounted in flowthrough diffusion cells using calcium and magnesium-free Phosphate Buffer Saline (PBS) as receptor fluid (flow rate 6 mLlh). Skin integrity was checked by TEWL (TransEpidermal Water Loss) before the hair dye application.

The following hair dye mixtures (prepared immediately before the application) were studied :

• the hair dye formulation 175303 containing the coupler (unlabelled + [14 C] _2 .84 ± 0 .45 %, w/w) associated to a primary intermediate (p-PHENYLENEDIAMINE 1 .94 % (w/w» applied in a 1/1 (w/w) mixture with the developer hydrogen peroxide (final concentration = 1 .38 ± 0.13 %, w/w), in order to study the penetration of the coupler under usual dyeing conditions,

• the hair dye formulation 175302 containing the coupler alone (unlabelled + [14C] _ 2 .99 ± 0.32 %, w/w) applied in a 1/1 (w/w) mixture with water (final concentration 1 .44 ± 0 .02 %, w/w), in order to study the penetration of the coupler itself.

• the hair dye formulation 175302 containing the coupler alone (unlabelled + [ 14C] _2 .99 ± 0.32 %, w/w) applied in a 1/1 (w/w) mixture with the developer hydrogen peroxide (final concentration = 1 .53 ± 0.06 %, w/w), in order to study the penetration of the coupler under oxidative conditions.

The hair dye mixtures were applied once at the dose of ca 20 mg/cm² (corresponding to ca 300 pg/cm2 of coupler) on the skin surface. Thirty minutes after application, the hair dye mixture remaining on the skin surface was removed following a well-standardized washing procedure.

Twenty four hours after application, percutaneous absorption of [ 14C]-2-METHYL-5- HYDROXYETHYLAMINO- PHENOL and/or [14C]-by-products was determined by measuring the concentration of the [ 14C]-coupler and/or [14C]-by-product by liquid scintillation counting in the following compartments : Skin excess, Stratum corneum (tape stripping), Epidermis, Dermis and Receptor fluid.

The kinetics of [14C]-2-METHYL-5-HYDROXYETHYLAMINO-PHENOL and/or [ 14C]-byproducts diffusion in the receptor fluid was also evaluated by liquid scintillation counting of the receptor fluid fractions up to 24 hours.

Most of the radio-labelled Imexine OAG applied on the skin surface was removed with the washing procedure (skin excess, 95.7%, 93.4%, and 94.4% of the applied dose for a total recovery rate of 96.8%, 94.4%, and 95.7% in use, oxidative and non-oxidative conditions, respectively).

The penetrated amounts (amounts measured in the receptor fluid) were 1.11 ± 0.62 (0.42% of the applied dose), 1.18 ± 0.34 (0.39%), and 2.38 ± 1.68 µgeq/cm²)  (0.83%) in use, oxidative, and nonoxidative conditions, respectively.

The absorbed amounts (dermal delivery, sum of the amounts measured in the living epidermis/dermis and receptor fluid) represented

- 2.58 ± 1.03 µgeq/cm²) (0 .95 ± 0.39 % of the applied dose) for 175303 [14C] + H202, in use condition

- 3.44 ± 1.89 µgeq/cm²)  (1 .21 ± 0.68 % of the applied dose) for 175302 [14C] + H2O, non oxidative condition

- 2.35 ± 0.79 µgeq/cm²) (0.77 ± 0.29 % of the applied dose) for 175302 [14C] + H202, oxidative condition