1-[2-(2-chloroethoxy)phenylsulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)urea;triasulfuron (ISO)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 Jun 2012 to 17 Jul 2012

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

Version / remarks:

2008

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide

EC Number:

617-298-9

Cas Number:

82097-50-5

Molecular formula:

C14H16ClN5O5S

IUPAC Name:

2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide

Test animals

Species:

rat

Strain:

Wistar

Remarks:

CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
-Females nulliparous and non-pregnant: yes
-Age/weight at dosing: Young adult rats, 9-10 weeks old / 217-229 g
-Housing: Individual caging
-Diet: complete diet for rats ad libitum
-Water: Tap water from municipal supply, provided in 500 mL bottles ad libitum
-Acclimatisation period: At least 5 days

ENVIRONMENTAL CONDITIONS:
-Temperature: 21.9 - 25°C
-Humidity: 38 – 70 %
-Air changes: 15-20 air exchanges/hour
-Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: from 26 June 2012 to 17 July 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

VEHICLE
- Amount of vehicle: 10 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4, and 6 hours after dosing and once each day for 14 days thereafter
- Necropsy of survivors performed: All animals were euthanised at the end of the observation period by exsanguination under pentobarbital anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets. The body weight of animals found dead were recorded at necropsy.
- Clinical signs including body weight: Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern were assessed.
Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The body weights were recorded on Days -1, 0 (beginning of the experiment), 7 and 14

Statistics:

Mean and Standard deviation was calculated for body weight and body weight gain. The LD50 was calculated using the AOT425StatPgm program.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the study

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

There were no treatment related effects on body weight or body weight gain

Gross pathology:

No treatment related macroscopic observations were recorded

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item was greater than 5000 mg/kg bw (limit dose) in female CRL:(WI) rats.

Executive summary:

In an OECD TG 425 acute oral toxicity study,performed under GLP, fasted female CRL:(WI) rats, 9-10 weeks old were given a single oral (gavage) dose of the test item, at dose levels of 5000 mg/kg. Single animals were dosed sequentially at no less than approximately 48 hour intervals. Animals were observed individually for up to 14 days thereafter and necropsies were performed on all surviving animals at the end of the study. No deaths occurred during the study.

Treatment with the test substance at the dose level of 5000 mg/kg bw caused vocalisation in one animal who was symptom free from 48 hours after treatment. The other two animals showed no clinical signs. There were no treatment related body weight changes. Body weights were within the range commonly recorded for this strain and age. No treatment related macroscopic observations were recorded in any animals dosed at 5000 mg/kg bw.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test item was found to be above 5000 mg/kg bw in male CRL:(WI) rats.