2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

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:

2003

Report date:

2003

Materials and methods

Objective of study:

absorption

metabolism

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.7485 (Metabolism and Pharmacokinetics)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

EC Number:

264-980-3

EC Name:

2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide

Cas Number:

64628-44-0

Molecular formula:

C15H10ClF3N2O3

IUPAC Name:

3-(2-chlorobenzoyl)-1-[4-(trifluoromethoxy)phenyl]urea

Details on test material:

[(4-trifluoromethoxy)aniline-UL-14C] triflumuron

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Wistar Hanover rats (approximately 8 weeks old and weighing 130 to 180 g), obtained from
Charles River Laboratories, Raleigh, NC, were acclimated for approximately 7 days prior to dosing. During the acclimation period, each rat was examined by a veterinarian. Food (Rodent Diet, PMI Nutrition International, Inc., St. Louis, MO) and water were available ad libitum. The acclimation and test rooms were maintained with a 12-hour light/dark cycle, a 23±2C temperature, and 40±5% relative humidity. Immediately prior to dosing, the rats were fasted for approximately 12 hours.
Following dosing, the rats were housed in individual Nalgene rodent metabolic cages (Harvard
Bioscience, South Natick, MA) which allowed collection of urine, feces, and respired gases. After
dosing, food and water were available ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The metabolism of triflumuron was generally rapid.

Details on distribution in tissues:

No volatile metabolites were detected, and no mineralization was observed. Residue levels in all tissues were highest in spleen, lung, and fat. While total whole blood residues were high, the level in blood plasma dropped to >0.10 ppm within 24 hours of dosing. Metabolites were formed mainly through hydrolysis followed by oxidation and subsequent conjugation to allow for ready excretion.

Details on excretion:

In all dose groups, between 45% and 82% of the dose was excreted within 24 hours. The route of excretion in males appeared to be in part dependent on the dose regime; a single high dose was mainly excreted as unchanged parent in feces while multiple dosing resulted in slightly greater urinary excretion compared to a single low dose. Females excreted slightly less of the dose in urine, over a longer period of time, than males. Over the course of each experiment, at least 95% of the dose was excreted.

Applicant's summary and conclusion

Conclusions:

Based on the results of a toxicokinetic assessment according to OECD guideline 417 and GLP principles, it is concluded that oral uptake is rapid. Triflumuron is metabolized and excreted for the largest part within 24 hours.