N-phenyl-N'-[(phenylamino)sulfonyl]urea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16. January - 22 June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-phenyl-3-(phenylsulfamoyl)urea

EC Number:

813-358-5

Cas Number:

4886-26-4

Molecular formula:

C13H13N3O3S

IUPAC Name:

1-phenyl-3-(phenylsulfamoyl)urea

Test material form:

solid: particulate/powder

Details on test material:

- State of aggregation:
- Particle size distribution:
- Mass median aerodynamic diameter (MMAD):
- Geometric standard deviation (GSD):
- Shape of particles:
- Surface area of particles:
- Crystal structure:
- Coating:
- Surface properties:
- Density:
- Moisture content:
- Residual solvent:
- Activation:
- Stabilisation:
- Other:

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Research Models and
Services, Germany GmbH, Sandhofer Weg 7,
D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes/
- Age at study initiation: Young healthy adult rats, 9 weeks old
- Weight at study initiation: 210-243 g
- Fasting period before study: no
- Housing: standard housing conditions, 3 animals per cage
- Diet and Water:Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice –
breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest,
Germany (Batch number: 141 8884, expiry date: 31 January 2017 and Batch number:
484 14771, expiry date: 30 June 2017), ad libitum, and tap water from the municipal
supply, as for human consumption from a 500 ml bottle, ad libitum. The food is
considered not to contain any contaminants that could reasonably be expected to affect
the purpose or integrity of the study. Copies of the Certificate of Analyses are retained
in the archive at CiToxLAB Hungary Ltd.
- Acclimation period: At least 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 25.8 °C
- Humidity (%): 26 – 66 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: not stated
- Lot/batch no. (if required): A0348063
- Purity: not applicable


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
A limit test was not be performed as the toxicity of the test substance was unknown at
2000 mg/kg bw. In agreement with the Sponsor, in the main test a starting dose of 300
mg/kg bw was selected based on the results of a previous in vitro cytotoxicity test
conducted at the Test Facility

Doses:

300 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical Observations
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6
hours after dosing and daily for 14 days thereafter or up to death. Individual
observations were performed on the skin, fur, eyes, mucous membranes, respiratory,
circulatory, autonomic and central nervous system, somatomotor activity and
behaviour pattern. Particular attention was directed to observation of tremors,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight Measurement
The body weight was recorded on the day before treatment (Day -1), on the day of the
treatment (Day 0), weekly thereafter and at necropsy (Day 14) or at death.

- Necropsy of survivors performed: yes

Statistics:

none applied

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

N-phenyl-N'-[(phenylamino)sulfonyl]urea did not cause mortality at a dose level of 300 mg/kg bw. At a dose level of 2000 mg/kg bw 1 out of 6 animals was found dead on Day 0 (within 4 hours after treatment).

Clinical signs:

other: No findings were recorded at a dose level of 300 mg/kg bw, all animals were symptomfree during the experiment. The following clinical signs were recorded at a dose level of 2000 mg/kg bw: slightly decreased activity (6/6 animals), hunched back (6/6 animal

Gross pathology:

One animal (ID #6060) dosed at 2000 mg/kg bw was found dead 4 hours after dosing on Day 0. White creamy material mixed with diet in the stomach, white liquid material mixed with diet in the duodenum, jejunum and ileum were considered to be administered test item.
In addition, diffuse dark red discoloration of the non-collapsed lungs was regarded as agonal/post mortem changes. No macroscopic changes were seen in rats dosed at 300 mg/kg bw as well as in surviving animals dosed at 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item N-phenyl-N'-[(phenylamino)sulfonyl]urea was found to be greater than 2000 mg/kg bw in female Crl:WI Wistar rats.
According to the GHS criteria, classification of N-phenyl-N'-[(phenylamino)sulfonyl]urea can be ranked as "Category 5" for acute oral exposure.

Executive summary:

The single-dose oral toxicity study with N-phenyl-N'-[(phenylamino)sulfonyl]urea was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in female Crl:WI Wistar rats.

Two groups of three female rats were treated with the test item at a dose level of 300 mg/kg body weight (bw) (Group 1 and Group 2) and two groups of three female rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 3 and Group 4).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test

item was administered at the dose level of 300 and 2000 mg/kg bw. Initially, three females (Group 1) were treated at a dose level of 300 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore, another three animals (Group 3) were treated at a dose level of 2000 mg/kg bw. As only one mortality was observed, a confirmatory group (Group 4) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore, no further

testing was required according to OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0, 7 and before necropsy (Day 14) or at death. All animals were subjected to a necropsy

and a macroscopic examination.

RESULTS

Mortality

N-phenyl-N'-[(phenylamino)sulfonyl]urea did not cause mortality at a dose level of 300 mg/kg bw. At a dose level of 2000 mg/kg bw 1 out of 6 animals was found dead on Day 0 (within

4 hours after treatment).

Clinical Observations

No findings were recorded at a dose level of 300 mg/kg bw, all animals were symptom-free during the experiment. The following clinical signs were recorded at a dose level of 2000 mg/kg bw: slightly decreased activity (6/6 animals), hunched back (6/6 animals), piloerection (5/6 animals), diuresis (5/6 animals) on Day 0. From Day 1 up to the end of the observation period all surviving animals were symptom-free.

Body Weight and Body Weight Gain

Body weight gains of N-phenyl-N'-[(phenylamino)sulfonyl]urea treated surviving animals during the study showed no indication of a test item-related effect.

Macroscopic Findings

One animal dosed at 2000 mg/kg bw was found dead 4 hours after dosing on Day 0.

White creamy material mixed with diet in the stomach, white liquid material mixed with diet in the duodenum, jejunum and ileum were considered to be administered test item. In addition, dark/red discoloration of the non-collapsed lungs was regarded as agonal/post mortem. No macroscopic changes were seen in rats dosed at 300 mg/kg bw as well as in surviving animals dosed at 2000 mg/kg bw.