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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 August 2013 - 14 November 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 2-1-1

Version / remarks:

Novembre 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[(5-chloroquinolin-8-yl)oxy]acetic acid

Cas Number:

88349-88-6

Molecular formula:

C11H8ClNO3

IUPAC Name:

[(5-chloroquinolin-8-yl)oxy]acetic acid

Test material form:

solid: particulate/powder

Remarks:

powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): X204558
- Physical state: Tan solid
- Analytical purity: 98.3% ± 0.03% wt/wt
- Purity test date: 14 September 2014
- Lot/batch No.: 2GHB0002
- Storage condition of test material: in its original container at ambient condition

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 184.4 - 208.2 g
- Fasting period before study: overnight fasting prior to dose administration
- Housing: Three rats/cage in polypropylene rat cages covered with stainless steel grid top
- Diet ad libitum rat pellet feed Teklad certified Global High Fiber Rat and Mice Feed
- Water ad libitum UV sterilized water filtered through Kent Reverse Osmosis water filtration system
- Acclimation period: 7 days for set I rats (rat N° 1, 2 and 3) and 9 days for set II rats (rat N° 4, 5 and 6)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 65 to 66
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 28 August 2013 To: 20 September 2013

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% (w/v) in distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The test item was solid and mixed in 0.5% (w/v) carboxy methyl cellulose (CMC) in distilled water.
- Amount of vehicle (if gavage): Individual dose volume was adjusted according to body weight and dose level.

CLASS METHOD
- Rationale for the selection of the starting dose: Set I rats were given a single dose of 2000 mg/kg body weight. As no mortality was observed up to approximately 48 hours after dosing at this dose level, three female rats from set II were administered the same dose of 2000 mg/kg body weight. As no mortality was observed at this dose level further testing was not required.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Six females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, the rats were observed twice a day for morbidity and mortality
- Necropsy of survivors performed: yes, All animals were subjected to a gross pathological examination consisting of an external examination and opening of abdominal and thoracic cavities
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The clinical signs were recorded once a day. Individual body weight was recorded prior to dosing on day 0 and on days 7 and 14.

Statistics:

Not required.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

No treatment-related clinical signs were observed.

Body weight:

There were no apparent effects on body weight.

Gross pathology:

External examination of terminally sacrificed female rats did not reveal any abnormality of pathological significance.
Visceral examination of terminally sacrificed rats did not reveal any lesion of pathological significance.

Other findings:

No other findings reported.

Any other information on results incl. tables

There was no mortality; the LD50 was therefore considered to be > 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance in Wistar rats was found to be greater than 2000 mg/kg bw. Classification according to the CLP Regulation is therefore not required.

Executive summary:

An acute oral toxicity study was conducted with X204558 (cloquintocet acid), according to OECD 423. Two sets of fasted Wistar rats (3 females/set) were given a single oral dose of X204558 in 0.5% (w/v) carboxy methyl cellulose (CMC) in distilled water at a dose of 2000 mg/kg bw and observed for 14 days.

There were no treatment-related mortality, clinical signs or changes in body weight recorded. Necropsy findings of the terminally sacrificed rats did not reveal any abnormality of pathological significance. The acute oral LD50 of X204558 (cloquintocet acid) in Wistar rats was found to be greater than 2000 mg/kg bw. Based on the results of this study, cloquintocet acid is not classified for acute oral toxicity according to the CLP Regulation.