Reaction mass of Fatty acids, montan-wax and Fatty acids, montan-wax, ethylene esters and Fatty acids, montan wax, mixed esters with fatty acids C16-18 and ethylene glycol and Fatty acids, montan-wax, stearyl esters and Montan wax

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

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:

publication

Title:

Unnamed

Year:

1993

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

Study on distribution and excretion of octacosanol after oral uptake

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Octacosan-1-ol

EC Number:

209-181-2

EC Name:

Octacosan-1-ol

Cas Number:

557-61-9

IUPAC Name:

octacosan-1-ol

Details on test material:

- Name of test material (as cited in study report): octacosanol

Radiolabelling:

yes

Remarks:

8-[14C]

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Funabashi Farm, Japan
- Age at study initiation: 4 weeks
- Weight at study initiation: 63-65 g
- Individual metabolism cages: yes
- Diet (ad libitum): Funabashi F2 pellet diet, Funabashi, Japan
- Water (ad libitum): drinking water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: tricapropyl-glycerol

Details on exposure:

VEHICLE
- Concentration in vehicle: 10 µCi 8-[14C]-octacosanol in 0,5 ml tricaproyl-glycerol
- Amount of vehicle (if gavage): 0,5 ml

Duration and frequency of treatment / exposure:

single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
10 µCi 8-[14C]-octacosanol in 0,5 ml tricaproyl-glycerol

No. of animals per sex per dose / concentration:

3

Control animals:

no

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired CO2
- Time and frequency of sampling: excreta continously for 7 days
- Other: distribution to organs and tissues (liver, kidneys, liver, spleen, heart, lungs, brain, gastrointestinal tract, muscle, adipose tissues: epididymal, perirenal and brown adipose tissue) sampling: 1, 2, 3 and 7 days after dosing

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The amount of radioactivity (representing the octacosanol and metabolites content) in organs and tissues was generally low (< 4% of administered dose per organ or tissue). One day after exposure, the highest amount of radioactivity was observed in the liver, followed by muscle. Based on the concentration (per g tissue) the adipose tissues revealed the highest concentration, especially the brown adipose tissue. This value declined within 7 days. Lower amounts were detected in all examined organs and tissues (in decreasing order: liver, digestive tract, spleen, kidney, heart, lung, brain, muscle).

Details on excretion:

The excretion via faeces represented 32.1% of the administered dose within 7 days after exposure, tho predominant part of it within 2 days. The expiration of 14C-CO2 was 15.1% and the urine contained 1.3% (sum of about 50% of the administered dose within 7 days). The summarised contents of organs and tissues at day 7 after dosing was about 3% .

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
After oral application of rats octacosanol was excreted mostly in faeces, lower amounts in urine and expired air. The substance was distributed throughout the whole body. Only low amonuts of radioacitivity were retained in the individual organs or tissues at day 7 after dosing (highest amount per gram in adipose tissue)

Executive summary:

When 12 male Wistar rats were orally exposed to radioactively labelled octacosanol, the substance was distributed throughout the whole organism. The highest concentration per g tissue was found in brown adipose tissue at day 1 after dosing. Only minor amounts of radioactivity were retained in all tissues after 7 days. About 50% of the administered dose were detected in excreta within 7 days after exposure (32.1% in feces, 1.3% in urine and 15.1% as CO2 in expired air).