Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1998-09-21 to 1999-01-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it generally followed OECD guideline 417 and was GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nexbase 2006 FG
- Substance type: Poly alpha olefins (1-decene homopolymer hydrogenated)
- Physical state: Liquid
- Analytical purity: Not reported
- Composition of test material, percentage of components: Not reported
- Lot/batch No.: Non-radiolabelled: 7059E; radiolabelled: 98BDR30B and 98BDR30C
- Expiration date of the lot/batch: Not reported
- Radiochemical purity (if radiolabelling): >97%
- Specific activity (if radiolabelling): Batch # 98BDR30B: (A) 0.68 µCi/mg, (B) 0.098 µCi/mg, (C) 0.0136 µCi/mg; Batch # 98BDR30C: 0.68 µCi/mg
- Locations of the label (if radiolabelling): Hydrogen
- Expiration date of radiochemical substance (if radiolabelling): Not reported
- Stability under test conditions: Unknown
- Storage condition of test material: Stored at -20 degrees Celsius
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Oxford, England
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 195 to 250 grams
- Housing: Individually in glass metabolism cages
- Individual metabolism cages: Yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 40 to 70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES: From: 1998-09-21 To: 1999-01-21

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Compound was administered undiluted.


Duration and frequency of treatment / exposure:
Single dose or 15 daily doses
Doses / concentrations
Remarks:
Doses / Concentrations:
30, 210, or 1500 mg/animal
No. of animals per sex per dose:
3 rats per sex per dose per time point
Control animals:
no
Positive control:
None
Details on study design:
- Dose selection rationale: None provided
- Rationale for animal assignment (if not random): Not reported
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Urine, faeces, blood, plasma, liver, kidney, fat, spleen, lymph nodes, gastrointestinal tract, cage washes, bile
- Time and frequency of sampling: 0.08, 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72, 120, and/or 168 hours



Statistics:
None performed

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, and 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

Conclusions:
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 faeces (70.03%) and GI tract (24.76%) at sacrifice (48 hours 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 of 3H-Nexbase 2006 FG in male rats. In each study, three rats were used per dose for each time point and endpoint measured.

Experiment 1. Male Fischer rats were administered a single oral dose of 3H-Nexbase 2006 FG at doses of 30, 210, or 1500 mg/rat.

Experiment 2. Male Fisher rats were administered a single intravenous dose of 3H-Nexbase 2006 FG (30 mg/rat).

Experiment 3. Male Fischer rats were administered Nexbase 2006 FG (210 mg/rat/day) for 14 days followed by a single dose of e of 3H-Nexbase 2006 FG.

 Experiment 4. Three rats had bile duct-canulation surgery prior to oral administration of 3H-Nexbase 2600 FG (210 mg/rat).

 

1. Very little of the administered dose was absorbed following single oral administrations of 30, 210, or 1500 mg/rat 3H-Nexbase 2006 FG. Maximum plasma radioactivity was measured at 8, 4, and 72 hours, respectively, with mean concentrations of 0.893, 2.243 and 6.720 µg equivalents/ml. Terminal rate constants of 81 and 93 hours could only be estimated for the 210 and 1500 mg/rat doses. The majority of the dose remained in the gastrointestinal (GI) tract and was excreted in the faeces by 168 hours with ≥ 92% of the dose recovered. Excretion was rapid with nearly all radioactivity collected by 48 hours for animals dosed with 30 or 210 mg 3H-Nexbase 2006 FG.  Excretion of the 1500 mg/rat dose took longer with radioactivity still collected at 168 hours. Urinary excretion were low (<1%). Although the majority of the dose was found in the gastrointestinal tract, radioactivity was also found in the liver, lymph nodes, fat, kidneys, and spleen.  Rats administered 210 or 1500 mg/rat 3H-Nexbase 2006 FG had oily fur shortly after dosing (this was also noted by increasing amounts of radioactivity in the fur).  While the oil was gone by morning in the 210 mg/rat group, it took 48-72 hours to decline after exposure to 1500 mg/rat. 

 

2. No pharmacokinetic analysis of plasma radioactivity was possible because the measured plasma radioactivity in 2 of the 3 rats did not exceed the limits of quantification 4 hours post-dosing. 

 

3. Mean overall recovery of radioactivity following repeated exposure to Nexbase 2006 FG was 94.88% (almost exclusively in the faeces) at 168 hours following the final dose of 3H-Nexbase 2006 FG. The pattern of excretion of radioactivity at the 210 mg/rat level was almost identical to the single dose excretion study (Experiment 1).

 

4. Following oral administration of a single dose of 3H- Nexbase 2600 FG (210 mg/rat) after bile duct-cannulation, the majority of the administered dose was recovered in the faeces (70.03%) and GI tract (24.76%) at sacrifice (48 hours post-dosing).  Very little of the dose (mean 0.01%) was recovered in the bile. The fraction of Nexbase 2600 FG absorbed from the GI tract was < 1%. The bile duct–cannulated rats ate and drank less than the other rats. 

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it generally followed OECD guideline 417 and was GLP compliant.