Acetic acid, 2-[(5-chloro-8-quinolinyl)oxy]-

Endpoint summary

Description of key information

A pharmacokinetic and metabolism study in rats is available. The study was conducted to determine absorption, distribution, metabolism, and excretion of cloquitocet acid following single and multiple oral doses and intravenous exposure. The study indicated that cloquintocet acid is rapidly and highly absorbed, poorly metabolised and readily eliminated in the urine from the rat, with very low tissue residues. Therefore, no bioaccumulation is predicted.
A dermal absorption study in rats is available. The study was conducted to determine the percutaneous absorption of cloquintocet acid after dermal exposure to a representative product concentrate and two field dilutions in addition to the examination of the kinetics of percutaneous absorption. The study indicated that cloquintocet is poorly absorbed through the skin and any absorbed dose is readily eliminated in the urine.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

86

Absorption rate - dermal (%):

1.64

Absorption rate - inhalation (%):

100

Additional information

The toxicokinentics and metabolism of cloquintocet acid was investigated according to OECD test guideline 417 (McCoy et al, 2014). The dermal absorption of cloquintocet acid was investigated according to OECD test guideline 427 (de Bie et al, 2014) including the kinetics of percutaneous absorption at 24, 72 and 168 hours post-application.

 

Absorption:

Orally administered cloquintocet acid was rapidly absorbed without any apparent lag time. The percent absorption of the orally administered dose of cloquintocet acid was 59-86%.

(McCoy et al, 2014)

Dermal absorption of cloquintocet acid was 0.63, 1.38 and 1.64% for the concentrate of a wettable granule formulation (451.5 g/Kg), the field dilution of 1.05 g/L and the field dilution of 0.15 g/L, respectively.

(de Bie et al, 2014)

Cloquintocet acid is of low volatility, therefore inhalation exposure is only predicted when the substance is used in situations in which liquid aerosols may be generated such as during application by spraying. If inhalation exposure occurs, absorption is potentially extensive. A default assumption of 100% inhalation absorption may be made for the purposes of the risk assessment.

 

Distribution:

Only 0.03-0.24% of the orally administered cloquintocet acid remained in the tissues after 168 hours (7 days) post-dosing. An average of 0.08-0.09% of the IV dosed cloquintocet acid remained in the tissues of the animals sacrificed 168 hours post-dosing.

(McCoy et al, 2014)

 

Metabolism:

A total of two radiochemical peaks were detected in the urine samples and a total of one radiochemical peak was detected in the fecal homogenate extracts. Parent cloquintocet acid was detected in the urine samples as well as the fecal homogenate extracts. The most abundant peak in the urine and fecal homogenate extract was positively identified as cloquintocet acid. The remaining peak in the urine radiochemical profiles accounted for < 1.6% of the radiolabeled administered dose in the rats, which has been tentatively identified as the acyl glucuronide conjugate of cloquintocet acid.

(McCoy et al, 2014)

 

Excretion:

The orally absorbed cloquintocet acid dose was rapidly excreted in urine (59-84% of the administered dose) without any difference between the sexes. A smaller percentage (16-42%) of the oral dose was eliminated in feces. The IV-administered cloquintocet acid was also rapidly excreted in urine (72-81% of administered dose). Only a small percent (12-17%) of the IV dose was eliminated in feces.

(McCoy et al, 2014)

The dermally absorbed cloquintocet acid dose was predominantly excreted in the urine. The radioactivity in the urine was a factor of 2 -2.5 higher than in the faeces. The majority of the radioactivity was excreted within the first 27 hours for all the groups.

(de Bie et al, 2014)