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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
Study period:
27 September 1979 to 29 July 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Objective of study:
other: distribution and excretion
Test guideline
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
Distribution and the routes and the rates of excretion of radio-labelled EBHP following a single oral dose to rats were determined by liquid scintillation counting.

No authorised test guidelines available at the time of the study. No reference for the methodologies cited in the study report.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ethylbenzene hydroperoxide (EBHP) purified from crude plant product (non-radiolabelled material)/ [14C]EBHP

- Analytical purity: 95%

- Impurities (identity and concentrations): 1-phenylethanol (1%) and acetophenone (4%)

- Radiochemical purity (if radiolabelling): = 98.0%.

- Specific activity (if radiolabelling): 36.5 µCi/mg

- Locations of the label (if radiolabelling): See attached the structure.

- Stability: As [14C]EBHP; Two plates, eluted in chloroform or dlchloromethane showed only one radlo-component, with Rf values identical to authentic EBHP standard.

Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration and frequency of treatment / exposure:
SIngle administration.
Doses / concentrations
Remarks:
Doses / Concentrations:
[14C]EBHP, approximately 29 mg/kg bw , 36.89 µCi, 1365 KBq.
No. of animals per sex per dose / concentration:
Six females (only one dose was used).
Control animals:
no

Results and discussion

Preliminary studies:
Not performed.
Main ADME resultsopen allclose all
Type:
excretion
Results:
the radioactivity: 86% in the urine, 5% in the feaces in the first 3 days. Less than 0.2% of the dose remained in the animals after 8 days.
Type:
distribution
Results:
The residues in the tissues (kidney, liver, intestine, fat, muscle, skin and remaining carcass) were low and depleted to below 0.1 µg/g in all samples examined after 8 days

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not examined in this test.
Details on distribution in tissues:
See Table 4.
Details on excretion:
See tables 1 - 3.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Not applicable.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results (assumption based on the mean total recoveryf radio activity 92.9%)
The results obtained in this study indicate that [14C]EBHP and its metabolites are rapidly excreted from rats given a single oral dose. The dominant excretion route was via the urine.
Executive summary:

To determine the routes and the rates of excretion of EBHP following a single oral dose to rats.

Six female rats were each given a single oral dose of [14C]EBHP (5.6 mg, approximately 29 mg/kg). The radioactivity in the urine and faeces was measured daily. The animals were killed in groups of two at one, three and eight days after dosing, and their blood, major organs and tissues were assayed for radioactivity.

[14C]EBHP was rapidly eliminated. 91% of the administered dose was eliminated within three days: 86% of the dose was excreted in the urine and 5% in the faeces.

Only 0.2% of the dose remained in the animals after eight days. The mean total recovery of the radioactivity was 93%.

A reliability of 2 is assigned.