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

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: OECD guideline no. 427 (Draft, 2000)

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:

Wistar Kyoto (WKY)

Sex:

female

Administration / exposure

Route of administration:

dermal

Vehicle:

other: acetone/water 1:1

Details on exposure:

Dermal application: Approximately 24 h prior to treatment, a 5 x 6 cm area of the fur on the back of the animals and a 4 x 4 cm area of the fur in the abdominal region was shaved. On the shaved skin on the back an area of 2.5 x 4 cm was marked as application site. The shaved area in the abdominal region served as negative control. Immediately prior to treatment, the application site was cleaned with a 10 % shampoo solution and water, and then dried. 10 mg/kg bw (1.5 % Hydroxyethyl-3,4-Methylenedioxyaniline HCl in acetone/water 1:1; 0.15 mg/cm²) was applied uniformly onto the skin of the application site. Application, exposure and removal were done under anaesthesia. After the treatment period of 30 minutes, the application site was rinsed with an aqueous shampoo formulation. During the entire study period, animals wore plastic collars to avoid licking of the treated area.

Duration and frequency of treatment / exposure:

Single application. Study duration 48 h (group 8), 72 h (groups 5-7) and 96 h (groups 1-4)

Doses / concentrations

Dose / conc.:

10 mg/kg bw/day

Remarks:

Group 4 and 8

No. of animals per sex per dose / concentration:

4 females per group for Mass balance studies (group 4)
5 females (group 8) for Toxicokinetics

Details on dosing and sampling:

Urine and faeces were collected at the following time intervals (group 4): 0-8, 8-24, 24-48, 48-72 and 72-96 h after administration, and the metabolite profiles were determined by means of HPLC. In the toxicokinetic groups, blood was sampled at 10, 20, 40 min and at 1, 2, 4, 8, 24, 48 and 72 hours after dosing.

Results and discussion

Main ADME results

Type:

absorption

Results:

5 % (equal to 8 µg/cm²) of the administered dose for dermal application

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The absorption after dermal application was slower compared to oral application, but still relatively fast, as the maximum blood levels were noted after 1 h.

Details on excretion:

The most important route of excretion of 14C- HYDROXYETHYL-3,4-METHYLENE-DIOXY-ANILINE HCL and its metabolites for all routes of administration was the urine. Excretion via faeces was significantly less important in all groups. Since the observed proportion of the radioactivity excreted through the faeces was similar after i. v. and after oral application, the amount found in the faeces after oral application is considered to represent phase II metabolites of the dye that have been excreted via the bile.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The metabolite profile in the urine samples and faeces extracts was similar between the different dosing routes. Only metabolised HYDROXYETHYL-3,4-METHYLENE-DIOXY¬ANILINE HCL was detected in urine and faeces, thus demonstrating that the test substance is rapid and extensively metabolised in the Wistar Kyoto rat.

Applicant's summary and conclusion

Conclusions:

After dermal application the absorbed amount of HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL was very limited, although the test item was applied with a penetration enhancer. Once absorbed, the routes and rates of elimination were similar for all three routes of administration (i.v., oral and dermal). No differences in the metabolite profile between the routes of administration or between gender were observed and no tendency for bio-accumulation was noted in this study.