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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 June 2012 to 12 July 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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

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:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 236 g and 273 g
- Housing: Individual caging
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance. Ad libitum
- Water: Tap water. Ad libitum
- Acclimatisation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.2 – 27.5°C
- Humidity: 44 – 70 %
- Air changes: 15-20 air exchanges per hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: from 28 June to 12 July 2012

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

tap water

Details on dermal exposure:

TEST SITE
- Area of exposure: Back
- Pre-treatment: Approximately 24 hours before treatment an area on the back of the rat was shaven
- % coverage: Approximately 10 % area of the total body surface
- Type of wrap if used: Sterile gauze pads, a patch with adhesive hypoallergenic plaster and semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, residual test item was removed, using body temperature water
- Time after start of exposure: 24 hours

VEHICLE
- Amount applied : 1 mL

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A clinical examination was performed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter. The body weight of all animals was recorded on Day 0 (beginning of the experiment) and on Days 7 and 14.
- Necropsy of survivors performed: All animals were subjected to gross macroscopic examination. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed
- Clinical signs including body weight: Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma

Statistics:

Means and their standard deviations were calculated for body weight and body weight gain

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred after the 24-hour dermal exposure to the test item in CRL:(WI) Wistar rats

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

There were no effects on body weight and body weight gain during the observation period

Gross pathology:

There was no evidence of any test item related observations at a dose level of 2000 mg/kg bw at necropsy. Pelvic dilatation of the right kidney was incidentally seen in 1/10 animal

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of the test item after single dermal administration was found to be greater than 2000 mg/kg bw in male and female CRL:(WI) Wistar rats

Executive summary:

In an OECD TG 402 acute toxicity study performed under GLP, single administration of the test item at a dose of 2000 mg/kg body weight was applied dermally to 5 male and 5 female CRL:(WI) rats, followed by a 14-day observation period. The test item was applied as supplied. The application period was 24 hours. Clinical observations were assessed in all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. All animals were euthanized and subjected to a gross macroscopic examination at the end of the 14-day observation period (Day 14).

On test day 0, the test item was applied at a single dose of 2000 mg/kg body weight applied uniformly over the skin and remained on the skin throughout a 24- hour exposure period.

No mortality occurred during the study. No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period and no treatment related skin irritation was observed in any animal throughout the study. Pelvic dilatation of the right kidney was incidentally seen in 1/10 animal.

The median lethal dose of the test item after a single dermal administration was found to be greater than 2000 mg/kg bw in male and female CRL:(WI) Wistar rats.