Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report that followed sound scientific principles.

Data source

Referenceopen allclose all

Reference Type:
study report
Reference Type:
Opinion of the SCF on hydrogenated poly-1-decene.
Scientific Committe on Food (SCF)
Bibliographic source:
Document SCF/ADD/MsAd/199 Final (July 12, 2001).

Materials and methods

Objective of study:
Test guideline
equivalent or similar to
OECD Guideline 417 (Toxicokinetics)
GLP compliance:

Test material

Details on test material:
Name of test material as cited in the report: Nexbase 2006 FG
Substance type: 1-decene homopolymer, hydrogenated

Test animals

Fischer 344

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on exposure:
compound administered undiluted
Duration and frequency of treatment / exposure:
single dose or 15 daily doses
Doses / concentrations
Doses / Concentrations:
30, 2010, or 1500 mg/animal
No. of animals per sex per dose:
3 rats per sex per dose per time point
Control animals:

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
very little of the dose was absorbed in any of the studies
Details on distribution in tissues:
What little was absorbed was found in the liver, fat, lymph nodes, kidney spleen
Details on excretion:
The majority of the test compound was excreted into the faeces without being absorbed (>92%). Urinary excretion was low (<1%). Very little of the dose was recovered in the bile (0.01%).

Applicant's summary and conclusion

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Very little of orally administered Nexbase 2006 FG was absorbed after either a single or multiple dose. The majority of the administered dose was recovered in the feces (70.03%) adn GI tract (24.7%) at sacrifice (48h post dosing). Very little of the dose (mean 0.01%) was recovered in the bile
Executive summary:

This study report describes the experimental procedures and results of 4 studies designed to assess the toxicokinetic profile of3H-Nexbase 2006 FG in male rats. In each study, three rats were used per dose for each time point and endpoint measured.

The test compound was prepared by catalytic reduction, using a mixture of tritium and hydrogen, of a mixture of poly-1-decenes identical to that used in the manufacture of regular hydrogenated poly-1-decene. The radiochemical purity of 3H labelled hydrogenated poly-1 - decene used in the studies was >97%. Rats were given single oral doses (30, 120 or 1500

mg/rat) or an intravenous dose (30 mg/rat) of radiolabelled test compound to investigate absorption, toxicokinetics, tissue distribution and excretion. Other rats were given repeated daily oral doses of unlabelled compound (210 mg/rat) over 14 days followed by a single oral dose of labelled compound on day 15 to investigate the influence of repeated dosing. A fourth

group of rats with cannulated bile ducts were given a single oral dose of radiolabelled compound (210 mg/rat) to investigate biliary, urinary and faecal excretion.

Very low 3H concentrations were found in plasma after oral or intravenous dosing. The data were fitted to a kinetic model which gave a long half-life consistent with 3H2O in the body water of rats. As expected from tritium exchange, 3H2O accounted for most of plasma radioactivity, especially at 24 hours or more after dosing. At plasma Cmax values for oral dosing, tritium exchange represented about 0.1-0.5% of the dose. Non-volatile radioactivity (3H-hydrogenated poly-1-decene or its metabolites) accounted for only 14-31% of plasma radioactivity. At tissue Tmax values, most of the radioactivity within the carcass was associated with the gastrointestinal tract. The proportion of the dose in, or estimated to be in, fat, kidneys, lymph nodes and spleen was <0.1% of the dose. Only the liver (at 8 and 24 hrs after the 30 mg dose) contained >0.1% dose, with the proportion decreasing with increasing dose level, as expected for a poorly-absorbed compound. The amounts of radioactivity excreted in the urine (mean 0.16% of dose) and bile (mean 0.01% of dose) were very small. Faeces were the major route of elimination after oral dosing and represented an average of 102.0%, 94.9% and 91.7% of the dose at 30, 210 and 1,500 mg/rat respectively. Absorption of the dose can be estimated by summation of radioactivity present in urine, cage wash and

residual carcass (excluding the gastrointestinal tract): the averages were 0.31%, 0.07% and 0.95% for doses of 30, 210 and 1,500 mg/rat respectively. These estimates are <1% in total and represent a value lower than the level of impurities (<3%).

This study received a Klimisch score of 2 and is classified as reliable because it generally followed OECD guideline 417 and was GLP compliant.