3-[(phenylcarbamoyl)amino]phenyl 4-methylbenzenesulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 March 2017 - 12 April 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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

1998

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:

3-(3-phenylureido)phenyl 4-methylbenzenesulfonate

Cas Number:

2102522-55-2

Molecular formula:

C20H18N2O4S

IUPAC Name:

3-(3-phenylureido)phenyl 4-methylbenzenesulfonate

Test material form:

solid: particulate/powder

Details on test material:

Appearance: Off-white powder
Storage conditions: Controlled room temperature (15-25 °C, below 70 RH %)

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Cr1: WI Wistar rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes.
- Age at study initiation: 9 weeks old
- Weight at study initiation: 210 - 231 g
- Fasting period before study: On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed before treatment. The test material was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.
- Housing: 3 animals/cage in Type II. polypropylene/polycarbonate cages. Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 13 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20.1 – 25.0 °C
- Humidity: 35 – 67 %
- Air changes: 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

1% solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Preparation: Prepared from Methyl cellulose powder and distilled water
- Lot/batch no.: 511582

DOSE PREPARATION
- The test material was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the test facility on the day of administration.
- The formulation container was magnetic stirred continuously up to the end of dose administration procedures.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected to be that which is most likely to produce mortality in some of the dosed animals.
- In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
- Initially, three female animals were treated with 2000 mg/kg bw of the test material. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

In total 6 female animals were treated.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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. 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).
- Necropsy of survivors performed: Yes. Macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.
- Examinations performed: 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.

Statistics:

The method used was not intended to allow the calculation of a precise LD50 value. The test material was ranked into categories of Globally Harmonized Classification System (GHS (rev. 6) 2015). Clinical signs, body weight, body weight gain and gross macroscopic data were tabulated.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test material did not cause mortality at a dose level of 2000 mg/kg bw in any animal.

Clinical signs:

other: All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw.

Gross pathology:

There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw in any animal.

Any other information on results incl. tables

Clinical observations, dose level 2000 mg/kg bw, Treatment on Day 0, Sex: Female

Cage No.

Animal No.

Observations

Observation Days

0

1

2

3

4

5

6

7-14

Frequency

30 min

1h

2h

3h

4h

6h

1

7323

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

7324

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

7325

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

2

7326

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

7327

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

7328

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

 + = present

h = hour(s)

‘ = minute

Frequency of observation = number of occurrence of observation / total number of observations

 

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female rats.

Executive summary:

The acute oral toxicity of the test material was investigated according to the standardised guidelines OECD 423, EU Method B.1.Tris and EPA OPPTS 870.1100, and under GLP conditions, following the Acute Toxic Class Method. 

During the study, two groups of three female Crl:WI rats were treated with the test material at a dose level of 2000 mg/kg body weight (bw) (Group 1 and Group 2). 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 material was administered at the dose level of 2000 mg/kg bw. Initially, three females (Group 1) were treated at a dose level of 2000 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, no further testing was required.

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). All animals were subjected to a necropsy and a macroscopic examination.

Under the conditions of the study, the test material did not cause mortality at a dose level of 2000 mg/kg bw. All animals were symptom-free during the observation period at a dose level of 2000 mg/kg bw. There were no treatment related body weight changes. A slight decrease was detected in body weight between Day 7 and Day 14 in one animal however this fact was considered to have no toxicological significance. Body weights were within the range commonly recorded for this strain and age. There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw.

The acute oral LD50 of the test material was therefore determined to be > 2000 mg/kg bw in female rats.