2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-02-27 to 1979-04-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Principles of method if other than guideline:

Four animals per group were treated with the test article for 28 days and autopsied. The following organs and tissues of each animal were then used for residue analysis: Liver, Brain, Eyes, Blood, Fat of testes, Storage fat tissue.

GLP compliance:

no

Remarks:

prior to GLP

Test material

Test material information

Constituent 1

Reference substance name:

2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)

EC Number:

230-426-4

EC Name:

2,5-thiophenediylbis(5-tert-butyl-1,3-benzoxazole)

Cas Number:

7128-64-5

Molecular formula:

C26H26N2O2S

IUPAC Name:

5-tert-butyl-2-[5-(5-tert-butyl-1,3-benzoxazol-2-yl)thiophen-2-yl]-1,3-benzoxazole

Details on test material:

- Physical state: solid

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not indicated
- Age at study initiation: 7 to 8 weeks old at the starting date of administration
- Fasting period before study: overnight
- Housing: groups of 4 in special Macrolon cages (type 3, equiped with wire inset)
- Diet: rat food - NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: for a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 14/10

IN-LIFE DATES: From: 1979-03-29 To: 1979-04-25

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2%

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- The test substance was suspended.
- Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

VEHICLE:
- Carboxymethyl-cellulose 2 % (CMC)
- Volume: 5 mL/kg

Duration and frequency of treatment / exposure:

28 days, daily administration

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.025 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

0.25 mg/kg bw/day

No. of animals per sex per dose / concentration:

4 (see table below)

Control animals:

yes, concurrent no treatment

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: Liver, Brain, Eyes, Blood, Fat of testes, Storage fat tissue.
- Time and frequency of sampling: after 1, 7, 14 and 28 days

Analytical determination of the test article in the test material:
The test material was homogenized after addition of a measured amount of water using a high speed homogenizer. The slurry was then extracted with
n-hexane and the water free solvent measured using a fluorescence spectrophotometer.
Excitation wave length: 373 nm
Emission wave length: 400 - 450 nm

Results and discussion

Main ADME results

Type:

distribution

Results:

No accumulation of test material took place in the organs and tissues being examined.

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

With regard to the detection limits given in the table below no accumulation of the test article took place in the organs and tissues being examinated after 1 day of treatment. In respect of this results, samples of autopsy data taken after 7, 14 and 28 days of treatment were not analyzed.

Organ / Tissue	Dose Level (mg/kg bw)	Test material ng/g (ppb)
Blood	0.025	< 5
	0.25	< 5
Liver	0.025	< 30
	0.25	< 30
Storage Fat Tissue	0.025	< 30
	0.25	< 30
Fat of testes	0.025	<< 50
	0.025	<< 50
	0.25	<< 50
	0.25	<< 50
Eyes	0.025	< 5
	0.25	< 5
Brain	0.025	< 5
	0.25	< 5

No animal died during the study. The body weight gain of all treated animals was comparable to that of the controls. No toxic signs or symptoms were seen during the study. No substance related gross organ changes were seen.

No toxic signs or symptoms and no mortalities were seen during the study. The test material has therefore practically no toxicity to male rats by the this route of administration at the dose levels 0.25 mg/kg and 0.025 mg/kg.