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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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C-Dodecamethylpentasiloxane

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: Approximately 225 g when purchased.
- Fasting period before study: None
- Housing: No data
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): approximately 45%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: No data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
Single oral dose
Doses / concentrations
Remarks:
Doses / Concentrations:
600 mg/kg bw
No. of animals per sex per dose:
2 males only
Control animals:
no
Positive control:
None
Details on study design:
- Dose selection rationale: None given
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion); After dosing animals were immediately placed in a Roth-type glass metabolism cage.
- Tissues and body fluids sampled: urine, faeces, plasma, other organs/tissues, expired air.
- Time and frequency of sampling: samples of excreta and expired air collected for 96 hours after dosing. Animals euthanised after 96 hours and blood and tissues removed for determination of 14C, and examinations.

METABOLITE CHARACTERISATION STUDIES: not conducted
Statistics:
None described.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Approximately 25% of the administered dose was absorbed from the gastrointestinal tract.
Type:
distribution
Results:
Trace amounts of 14C activity were detected in various organs and tissues at the time of necropsy (96 hours after administration).
Type:
metabolism
Results:
Not investigated.
Type:
excretion
Results:
Approximately 74% of the dose was recovered from the faeces, while 23% was eliminated through the expired air. Only 2.2% was recovered in urine.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Based on total recovery in the urine, expired air and tissues, and assuming no biliary excretion, approximately 25% of the administered dose was absorbed from the gastrointestinal tract.
Details on distribution in tissues:
Trace amounts of 14C activity were detected in various organs and tissues (primarily those involved in excretion of the test substance) at the time of necropsy (96 hours after administration). No 14C was detected in plasma at the time of necropsy (96 hours). The liver and lungs had the highest 14C activity, which the authors concluded was equivalent to 73 and 16 µg of dodecamethylpentasiloxane equivalent per wet weight of tissue. The kidneys had the next highest concentration at 8 µg of dodecamethylpentasiloxane equivalent per wet weight of tissue. Overall recovery from tissues and organs was 0.09% of the administered dose.
Details on excretion:
Approximately 74% of the dose was recovered from the faeces, while 23% was eliminated through the expired air. Only 2.2% was recovered in urine. About 65 and 97% of the applied dose was eliminated within 24 and 48 hours, respectively. Therefore elimination was rapid.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

There were no signs of toxicity and no gross pathological findings relating to treatment.

Applicant's summary and conclusion

Conclusions:
In a toxicokinetic study that investigated the oral absorption, distribution and elimination of dodecamethylpentasiloxane in two male rats following a single gavage dose, the absorption was found to be approximately 25% of the administered dose (reliability score 2). Elimination was rapid (65 and 97% by 24 and 48 hours, respectively), so by 96 hours after dosing there were only trace amounts of the test substance in tissues and organs (0.09% of administered dose across all tissues and organs). Approximately74% of the administered dose was found in faeces, 23% in expired air and 2.2% in urine.