Chlorimuron ethyl

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2006

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 2-({[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)benzoate

EC Number:

618-690-2

Cas Number:

90982-32-4

Molecular formula:

C15H15ClN4O6S

IUPAC Name:

ethyl 2-({[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)benzoate

Test material form:

solid

Remarks:

White

Details on test material:

95 to >99% purity

Specific details on test material used for the study:

Analytical Purity: 97.4% by analysis; Lot # JULJUL05MA037

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Test animals Source: SAGE™, Boyertown, PA; Weight at study initiation: 178-221g; Fasting period before study: Overnight; Housing: Singly housed in plastic solid bottom polycarbonate cages; Diet: Purina Rodent Chow #5012; Acclimation period: 20-30 days

Environmental conditions: Temperature and Relative Humidity Ranges: 19-23°C and 30-44%, respectively; Photoperiod: 12 hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The sample was administered as a 40% w/w mixture in distilled water. Preliminary solubility testing conducted by EPSL indicated that mixtures in excess of 40% (i.e. 50-80%) were too viscous to be administered properly.

Doses:

175, 550, 1750, and 5000 mg/kg

No. of animals per sex per dose:

One rat was adminsitered 175, 550, and 1750 mg/kg and 3 rats were administered 5000 mg/kg

Control animals:

no

Details on study design:

Based on a limit dose of 5000 mg/kg, a Main Test was conducted using a default starting dose level of 175 mg/kg administered to one healthy female rat by oral gavage. Following the Up and Down procedure, one female each was dosed at 550 or 1750 mg/kg and three females were dosed at 5000 mg/kg. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice.

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Westat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable

Remarks:

No deaths

Mortality:

No deaths

Clinical signs:

other: No clinical signs of toxicity were observed

Gross pathology:

No changes

Other findings:

Reduced fecal volume noted on Days 1 and/or 2 for the rat dosed at the 1750 mg/kg level and two rats dosed at 5000 mg/kg

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is greater than 5000 mg/kg, the highest dose tested. According to the United Nations Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.

Executive summary:

An acute oral toxicity test (Up - and - Down Procedure; OECD 425) was conducted with rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route. Based on a limit dose of 5000 mg/kg, at the request of the Sponsor, a Main Test was conducted using a default starting dose level of 175 mg/kg administered to one healthy female rat by oral gavage. Following the Up and Down procedure, one female each was dosed at 550 or 1750 mg/kg and three females were dosed at 5000 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice.

Under the conditions of this study, the acute oral LD50 is greater than 5000 mg/kg of body weight in female rats.