Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-standard study; non-GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
other: toxicokinetic study
Mesamoll concentration was measured in fat and liver tissue at different timepoints during / after dosing
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
other: gavage/feed
Vehicle:
other: Lutrol
Duration and frequency of treatment / exposure:
Experiment1)
Single dose; 100 mg/kg; animals were killed 1, 3, 7, 14, 21 and 34 days after dosing

Experimet 2)
Single dose 1000 mg/kg; animals were killed 1, 3, 7, 14, 21 and 34 days after dosing

Experiment 3)
rats were fed diet containing 100 ppm compound for 49 days. Animals were sacrificed on day 1,3, 7, 14, 21 and 43 day.

Experiment 4a)
rats were fed diet containing 1000 ppm compound for 49 days. Animals were sacrificed on day 1,3, 7, 14, 21, 28, 35, 42 and 49. (see experiment 3)

Experiment 4b)
rats were fed diet conaining 1000 ppm compound for 27 days; thereafter rats were fed a diet without Mesamoll. Animals were sacrificed on day 1,3, 7, 14, 21, 28, and 43.
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg bw and 1000 mg/kg bw. (gavage study); 100 ppm and 1000 ppm feeding studies.
No. of animals per sex per dose:
30/sex/dose (gavage study); 30/sex/dose (feeding study 100 ppm); 50/sex/dose (feeding study 1000 ppm).
Control animals:
yes

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
20 - 30 % of the dose was excreted in the feces within 24 h.
Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 1st: The half-life of Mesamoll in fat tissue after single oral application 1000 mg/kg was 8 days.
Toxicokinetic parameters:
half-life 2nd: The half-life of Mesamoll in fat tissue after repeated oral application of 1000 mg/kg was 15 days.
Toxicokinetic parameters:
other: No accumulation was observed in the liver. 20 - 30 % of the dose was excreted in the feces within 24 h.

Any other information on results incl. tables

Mesamoll concentration in the liver was low in all experiments (actual concentration below or slidely above LOD)

Mesamoll concentrations in fat:

Experiment 1) Cmax 22 µg/g fat (day 3); Mesamoll concentration below LOD on day 14

Experiment 2) Cmax 65 µg/g fat (first timepoint measured; day 1); elemination half-life 8 days; 20 -30% of dose eleminated by feces during the first 24 h.

Experiment 3) Mesamoll concentrations in fat increased linear over time until the end of the experiment

Experiment 4a) Mesamoll concentrations in fat increased linear over time until day 21 (ca. 235 µg/g fat) and slightly increased therafter (ca. 290 µg/g fat on day 49).

Experiment 4b) Elemination half-life: approx. 15 days

Applicant's summary and conclusion

Executive summary:

The half-life of Mesamoll in fat tissue after single oral application and repeated oral application of 1000 mg/kg was 8 days and 15 days, respectively. No accumulation was observed in the liver. 20 - 30 % of the dose was excreted in the feces within 24 h.