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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
April - May 2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientific sound study design with restricted reporting.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Objective of study:
absorption
distribution
excretion
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified
Details on test material:
no data
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS

- Individual metabolism cages: yes
- Acclimation period: 4 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Male Wistar rats were administered single oral doses of 100 and 1000 mg/kg bw Hostanox SE 10, dissolved in corn oil (1 mL). After administration, animals were transferred to metabolic cages to collect urine and feces for up to 96 h.
Duration and frequency of treatment / exposure:
single application
Doses / concentrations
Remarks:
Doses / Concentrations:
100 or 1000 mg/kg bw
No. of animals per sex per dose:
no data
Control animals:
no
Positive control:
none
Details on study design:
Male Wistar rats were administered single oral doses of 100 and 1000 mg/kg bw Hostanox SE 10, dissolved in corn oil (1 mL). After administration, animals were transferred to metabolic cages to collect urine and feces for up to 96 h. To collect blood and organs, treated animals were sacrificed at 3, 6, 12, 24, 48, 72 and 96h.
Details on dosing and sampling:
Blood, urine and feces samples and organs were immediately frozen and kept at -20°C for analysis. To determine Hostanox SE 10 content, feces samples were lyophilized and the obtained residues were extracted with n-Pentane in a Soxhlett-extractor. The Pentane extracts were further purified using chromatography on silica gel cartridges. Hostanox SE 10 content was then quantified in the eluate from the silica gel purification step by GC/MS. Hostanox SE 10 concentrations were determined relative to the internal standard. Blood samples (150 - 500 µL) and organ homogenates (150 - 500 mg) were boiled for 15 min. after acidification with HCl. After 15 min. at 100 °C, the obtained samples were cooled to room temperature and extracted with Pentane. The Pentane phase was than purified by passing through a silica gel column. In the obtained eluate, Hostanox SE 10 was quantified by GC/MS.
Statistics:
none

Results and discussion

Preliminary studies:
none
Main ADME resultsopen allclose all
Type:
absorption
Results:
poor absorption since 93+/-14% of the applied amount was found in feces within 72 h
Type:
distribution
Results:
low concentrations observed in liver, kidney and mesentheric lymphnodes
Type:
excretion
Results:
major elimination pathway is with feces as unchanged parent compound

Toxicokinetic / pharmacokinetic studies

Details on absorption:
After oral administration of Hostanox SE 10 in single doses of 100 and 1000 mg/kg bw, detectable concentrations of Hostanox SE 10 in blood were observed aftter 3 h and peaked in the high dose at the 6 h sampling point. After 6 h, the blood levels of Hostanox SE 10 decreased to reach the limit of detection 24 h after administration of 100 mg/kg bw.
In animals administered 1000 mg/kg bw, Hostanox SE 10 was still detectable in blood 96 h after administration.
In general, the blood levels of Hostanox SE 10 were low and peaked at 250 pmol/mL blood even after application of the high dose of 1000 mg/kg bw.

Most of the administered dose (93 +/- 14 %) was recovered in feces within 72 h indicating poor absorption of Hostanox SE 10 from the gastro-intestinal tract and no or very limited metabolism.

Administration of hostanox SE 10 also caused a dose- and time-dependent increase of the test item mesentheric lymphnodes, liver and kidneys. However, organ levels were below 1.2 nmol/g organ and therefore very low, even after administration of the high dose.
Details on distribution in tissues:
Administration of hostanox SE 10 also caused a dose- and time-dependent increase of the test item mesentheric lymphnodes, liver and kidneys. However, organ levels were below 1.2 nmol/g organ and therefore very low, even after administration of the high dose.
Details on excretion:
The elimination of Hostanox SE 10 after the high dose followed first-order kinetics with an apparent half-life of 14 h. In all urine samples, the concentration of Hostanox SE 10 was below the limit of detection. Most of the administered dose (93 +/- 14%) was recovered in feces within 72 h.
Toxicokinetic parameters
Test no.:
#1
Toxicokinetic parameters:
half-life 1st: 14 h

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
n.a.

Bioaccessibility

Bioaccessibility testing results:
Most of the administered dose (93 +/- 14%) was recovered in feces within 72 h indicating a very limited bioaccessibility.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Hsotanox SE 10 absorption from gastro-intestinal tract is very limited after oral administration. The blood concentration peak is at 6 h after application. The elimination of Hostanox SE 10 follows first-order kinetics with an apparent half-life of 14 h. Most of the administered dose (93 +/- 14 %) is excreted via feces indicating a very low bioaccessibility. Concentration level in mesentheric lymphnodes, liver and kidney is below 1.2 pmol/o organ.
Executive summary:

The dispositon of Hostanox SE 10 was investigated in male Wistar rats after single oral doses of 100 and 1000 mg/kg bw. A dose-dependent increase in blood concentration of Hostanox SE 10 was observed and Hostanox SE 10 was cleared from blood within a parent half-life of 14 hours. Maximum blood concentrations of Hostanox SE 10 were reached within 6 hours and were 250 pmol/mL blood. Low concentrations of the test item were also observed in liver, kidney and mesentheric lymphnodes. The data indicate that Hostanox SE 10 absorption from the gastro-intestinal tract is very limited after oral administration and that the absorbed amount of the substance is rapidly cleared from blood. Most of the administered dose (93 +/- 14 %) was recovered in feces within 72 h supporting the observed low bioaccessibility.