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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 422
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine)
EC Number:
700-823-1
Cas Number:
55514-22-2
Molecular formula:
C36H24N6
IUPAC Name:
3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine)
Details on test material:
See 7.5 repeated dose toxicity
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
See Repeated dose toxicity

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % in water
Details on exposure:
See repeated dose toxicity
Duration and frequency of treatment / exposure:
See repeated dose toxicity
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300 and 1000 mg/kg bw/day
No. of animals per sex per dose / concentration:
8 animals per sex and per dose
Control animals:
yes, concurrent vehicle
Positive control reference chemical:
None
Details on study design:
See repeated dose toxicity
Details on dosing and sampling:
Blood samples for the determination of plasma levels of the test item were taken on day 1 and at the end of the treatment period. There were six sampling times in treated animals (0, 1, 2, 4, 8 and 24 h) and four sampling times in controls (1, 4, 8, and 24 h): . control animals were sampled at the end of the treatment period only, . treated animals were sampled on day 1 and at the end of the treatment period. Two animals/sex/group were sampled at each time-point, and each animal was sampled three times during each period. Four male and four female control animals were samples (at the end of the treatment period (at least 3 days before study termination to allow at least 14 hours fasting before sacrifice) and were taken on a different day to those of treated animals to avoid any possibility of contamination. In the control group, two animals/sex were sampled at each time-point, and each animal was sampled two times. Venous blood (approximately 1 mL) was collected from the orbital sinus of each animal, under light isoflurane anesthesia, into a tube containing lithium heparin. The blood was centrifuged and the plasma was divided into two aliquots of approximately 200 µL each in polypropylene tubes which kept at a nominal temperature of -80°C until analysis by CIT. After the last sampling occasion satellite animals were deeply anesthetized by an intraperitoneal injection of sodium pentobarbital, sacrificed by cervical dislocation and discarded without necropsy.

Results and discussion

Main ADME results
Type:
absorption
Results:
no significant systemic exposure to the test item

Toxicokinetic / pharmacokinetic studies

Details on absorption:
On determination of blood plasma concentration for toxicokinetic calculation, none of the male and female rats had significant blood plasma levels on day 1 or at the end of the treatment period (blood plasma level < 0.500 ng/mL, the limit of quantification), with the exception of two males and five females which had blood plasma levels slightly higher than the limit of quantification on study day 1 or at the end of the treatment period. Overall, it was considered that there was no significant systemic exposure to the test item.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
On determination of blood plasma concentration for toxicokinetic calculation, none of the male and female rats had significant blood plasma levels on day 1 or at the end of the treatment period (blood plasma level < 0.500 ng/mL, the limit of quantification), with the exception of two males and five females which had blood plasma levels slightly higher than the limit of quantification on study day 1 or at the end of the treatment period. Overall, it was considered that there was no significant systemic exposure to the test item.
Executive summary:

Three groups of eight males and eight females received also the test item for 5 weeks at dose-levels of 100, 300 or 1000 mg/kg/day for blood plasma concentration measurements on study day 1 and at the end of the treatment period (study week 5). The dosing volume was 10 mL/kg/day. 

Two animals/sex/group were sampled at each time-point, and each animal was sampled three times during each period.Venous blood (approximately 1 mL) was collected from the orbital sinus of each animal, under light isoflurane anesthesia, into a tube containing lithium heparin. The blood was centrifuged and the plasma was divided into two aliquots of approximately 200 µL each in polypropylene tubes which kept at a nominal temperature ofuntil analysis by CIT. After the last sampling occasion satellite animals were deeply anesthetized by an intraperitoneal injection of sodium pentobarbital, sacrificed by cervical dislocation and discarded without necropsy.

The concentration of WP30 was determined in plasma using LC-MS/MS method.On determination of blood plasma concentration for toxicokinetic calculation, none of the male and female rats had significant blood plasma levels on day 1 or at the end of the treatment period (blood plasma level < 0.500 ng/mL, the limit of quantification), with the exception of two males and five females which had blood plasma levels slightly higher than the limit of quantification on study day 1 or at the end of the treatment period