8-Chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Remarks:

Bone Marrow Exposure Evaluation in the Mouse

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Objective of study:

tissue distribution

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Deviations:

no

Remarks:

Exceptions include the use of a minimum design to establish the presence or absence of test substance concurrent with the conduct of the bone marrow micronucleus study (OECD 474).

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Cas Number:

353258-35-2

Molecular formula:

C9H4ClF3N2O2

IUPAC Name:

8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid

Specific details on test material used for the study:

Test substance: IN-QEK31-011
Batch No.: SG0312574
Purity: 98.2%

Radiolabelling:

no

Test animals

Species:

mouse

Strain:

other: Crl:CD1(ICR)

Details on species / strain selection:

The Crl:CD1(ICR) mouse has been selected based on extensive experience with this strain at the test facility and comparison with companion toxicity studies.

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.1% Tween-80 in 0.5% aqueous methylcellulose

Duration and frequency of treatment / exposure:

Single dose; At 4 hours after dosing, the animals were sacrificed and blood was collected.

Doses / concentrations

Dose / conc.:

500 mg/kg bw/day

No. of animals per sex per dose / concentration:

Vehicle control (0 mg/kg bw): 1/sex
500 mg/kg/bw: 4/sex

Control animals:

yes, concurrent vehicle

Statistics:

Group data are represented as Mean ± SD. No additional statistical analysis was done.

Results and discussion

Main ADME results

Type:

distribution

Results:

Bone marrow exposure in male and female mice was evident based on the presence of quantifiable test item in pooled plasma samples at 4 hours after a single oral gavage administration of 500 mg/kg bw.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The concentration of the test item in pooled plasma samples were 46100 ng/mL and 38200 ng/mL in male and female mice, respectively. The results from this study demonstrate target tissue exposure in mice at dosing conditions equivalent to those used in the concurrent mammalian erythrocyte micronucleus study.

Applicant's summary and conclusion

Conclusions:

The results from this study demonstrate target tissue exposure in mice.

Executive summary:

The test substance was being tested in a mouse bone marrow micronucleus study administered at single oral gavage doses of 500, 1000, or 1300 mg/kg body weight (bw). The current study investigated the target tissue exposure via plasma to the test item in male and female mice after oral administration (4 mice/sex). The targeted dose level was 500 mg/kg bw. The dose was prepared with 0.5% methylcellulose and 0.1% Tween-80 in water and administered at an approximate volume of 10 mL/kg bw. The dose concentration and 1.5-hour stability was confirmed by ultra-high performance liquid chromatography (UHPLC) with ultraviolet (UV) detection. Blood was collected 4 hours after dose administration, plasma was pooled (4 mice/sex), and samples were submitted for quantitation by UHPLC with tandem mass spectrometry detection (LC/MS/MS).

Bone marrow exposure in male and female mice was evident based on the presence of quantifiable test item in pooled plasma samples at 4 hours after single oral gavage administration of 500 mg/kg bw. The results from this study demonstrate target tissue exposure in mice at dosing conditions equivalent to those used in the concurrent mammalian erythrocyte micronucleus study.