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

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

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

Objective of study:

absorption

metabolism

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.7485 (Metabolism and Pharmacokinetics)

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

yes

Radiolabelling:

yes

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.

Route of administration:

oral: gavage

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.

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.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2002-01-16 to 2002-03-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Objective of study:

absorption

distribution

Qualifier:

according to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Version / remarks:

August 1998

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.7485 (Metabolism and Pharmacokinetics)

Version / remarks:

April 04, 1984

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

yes

Species:

rat

Strain:

Wistar

Remarks:

Hsd/Cpb: WU

Sex:

male

Details on test animals or test system and environmental conditions:

Breeder: Harlan-Winkelmann GmbH, 33178 Borchen, FRG
Rationale: The experiment is recognized as an applicable basic test system for the evaluation of possible hazard to human health
Age: 7 to 8 weeks at time of delivery
Weight: about 200 g at the radioactive administration
Acclimation: about 7 days
Rooms: The animals were held under conventional hygienic conditions in airconditioned rooms at approximately 18 °C – 25 °C and humidity of 27 – 65%, at a 12 hours photocycle and 10 – 15 fold air change per hour.
Cages: After administration of the radiolabelled test compound, the rats were kept individually in Makrolon metabolism cages, which allowed for a separate and quantitative sampling of the excreta.
Diet: The rats were fed ad libitum with rat/mice maintenance long life diet; ca. 18 g per day and animal. They were fasted for approximately 16 hours prior to dosing.
Water: Tap water was given ad libitum

Route of administration:

oral: gavage

No. of animals per sex per dose / concentration:

7 rats in total

The kinetic behaviour of triflumuron in male rats after a single oral dose was characterized by the following facts:
- different distribution of the radioactivity within the body with higher preference to all fatty tissues and liver as the main organ for degradation and kidney as the responsible organ for excretion,
- maximum concentrations in most organs and tissues 4 – 8 hours after dosing,
- in fatty tissues, highest concentrations of radioactivity detected 8 – 24 hours after
administration; by the end of experiment still higher values found in the brown, perirenal and intestinal fat by comparison with the blood level,
- relatively low concentrations in the organs and most tissues, compared to the
administered amount,
- possible binding of the parent compound and/or metabolites to blood components,
- no intensive blackening of glandular organs or tissues and those which are involved
in the regulation of hormones (e.g. adrenal, testis, or thyroid gland)
- long lasting enterohepatic circulation between the small intestine and liver,
- almost complete excretion of radioactivity via urine and faeces.

Conclusions:

Based on the results of a toxicokinetic study according to OECD/EC guidelines and GLP principles, it can be concluded that Triflumuron showed a preference to distribute (highest concentration after 8 – 24 hours) to liver, kidneys and to blood. The maximum concentration in most organs and tissues was reached between 8 and 24 hours. There was no preference for
glandular organs involved in the regulation of hormones. No significant accumulation for triflumuron was found in any organ.

Description of key information

Absorption, Distribution, Excretion and Metabolism of Triflumuron was extensively studied and evaluated (EFSA Journal 2011;9(1):1941). 

The results of two toxicokinetic studies are summarized, both studies were conducted according to relevant guidelines and under GLP principles. 

The data indicate rapid uptake of the substance via the oral route, and quick elimination. No bioaccumulation was found in these studies.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential