2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

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

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

comparable to guideline study: OECD Guideline 427 (Skin Absorption: In Vivo Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride

EC Number:

303-085-5

EC Name:

2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride

Cas Number:

94158-14-2

Molecular formula:

C9H11NO3.ClH

IUPAC Name:

2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride

Test material form:

solid: crystalline

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Duration of exposure:

Exp. A, B, C, D: Single dermal application for 30 min; total study period 72 h
Exp. E: single oral application (gavage); total study period 72 h

Doses:

Exp. A: Formulation without H2O2: 1.0 %, 10 mg/animal; 1.1 mg/cm2
Exp. B: Formulation with H2O2: 1.0 %, 10 mg/animal; 1.1 mg/cm2
Exp. C: Solution in water: 3.33 %, 10 mg/animal; 1.1 mg/cm2
Exp. D: Solution in water: 3.33 %, 10 mg/animal; 1.1 mg/cm2
Exp. E: Solution in water: 3.33 %, 51.02 mg/kg bw

No. of animals per group:

3

Results and discussion

Any other information on results incl. tables

Exp. A, B, C:

Total recovery of the applied radioactivity was good with recovery rates between 96.5 and 98.1 %.

The majority of the applied dose (95.9 to 97.1 % of the applied amount) was recovered in the washing solutions.

The amount of radioactivity remaining at the application site (skin) for the water solution represented 1.68 % of the applied dose. The respective figures for formulations with and without hydrogen peroxide were 0.56 % and 0.34 %, respectively.

0.314 %, 0.05 % and 0.345 % of the applied doses were eliminated via urine and faeces within 72 h in experiment A, B and C, respectively. The lowest absorption rate was obtained in the formulation containing H₂O₂. Radioactivity was mainly excreted via urine (84 – 99 % of the total amount eliminated). Elimination was fast, as 82 - 93 % of the total amount eliminated was excreted within the first 24 hours.

Excretion via faeces was of less importance representing 8.5 to 16 % of the absorbed dose.

The radioactivity remaining in the carcass was very low 72 hours after administration (0.005 % of the administered dose for exp. A and C, 0.002% of the administered dose for exp. B). Residues in organs were mostly below the detection limit, with highest concentrations noted for kidneys. No relevant differences were noted between males and females.

Based on these results, a cutaneous absorption rate of 3.5* µg/cm² (equal to 0.318 %), for the formulation without H₂O₂, of 0.59 µg/cm² (equal to 0.053 %) for the formulation with H₂O₂and of 3.95 µg/cm² (equal to 0.351 %) for the pure dyestuff in aqueous solution were obtained based on the bioavailable amounts (carcass, urine and faeces).

If, as a conservative assumption, the mean amounts found in urine, faeces, residual carcass and in the total skin including the application site were considered as bioavailable, a cutaneous absorption of 6.74 µg/cm² (equal to 0.613 %) was calculated for the commercial hair dye formulation with hydrogen peroxide. The respective figure for the formulation without hydrogen peroxide was 7.24 µg/cm² (equal to 0.658 %).

* Remark: In the report a value of 2.9 µg/cm² was given by mistake

 

Exp. D and E

Thehighestconcentration of the test compound in the blood was observed after 35 min, the first time point of sampling, after dermal as well as after oral application of the test substance (experiment D and E) and declined with an initial half-life of 1 h after cutaneous and about 1.5 h after per-oral administration. The highest concentration observed in the blood after oral application was about 70-fold higher than the highest value observed after dermal application.

Applicant's summary and conclusion

Conclusions:

When applied dermally to rats in a commercial hair dye formulation in the presence of hydrogen peroxide, 0.59 µg/cm² HYDROXYETHYL-3,5-METHYLENEDIOXYANILINE HCL become bioavailable based on the amounts determined in urine, faeces and carcass. When applied in different vehicles, i.e. a formulation without hydrogen peroxide or an aqueous solution, dermal absorption is higher, with values of 3.5 µg/cm² and 3.95 µg/cm², respectively. Excretion takes place predominantly via urine and to a minor extent via faeces. Excretion via urine is fast, as 82 to 93 % are excreted within the first 24 hours. Low tissue residue levels were noted, indicating that no relevant bio-accumulation has to be expected after dermal administration.Based on the assumption that the total amount found in the skin will become bioavailable, an amount of 6.74 µg/cm² HYDROXYETHYL-3,5-METHYLENEDIOXYANILINE HCL was calculated from the results of the experiment with commercial hair dye formulation in the presence of hydrogen peroxide. Although the tested concentration was below the maximum intended concentration in oxidative hair dye formulations (1% vs. 1.5%), this value was used for the calculation of the SED in the risk assessment. For the following reasons this value is still assumed to be a conservative estimate of the dermal penetration of HYDROXYETHYL-3,5-METHYLENEDIOXYANILINE HCL. The total amount found in the skin was considered as bioavailable, which is 11 fold higher than the amount absorbed (sum of amounts from urine, faeces, carcass). 2. The amount accumulated over a period of 72 hours is compared with the NOAEL derived from daily dosing in a repeated dose oral toxicity study. 3. Rat skin is known to overestimate the skin penetration in humans by a factor of 2 to 3.