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Toxicological information

Basic toxicokinetics

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
Qualifier:
according to guideline
Guideline:
other: OECD guideline no. 427 (Draft, 2000)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
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.

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