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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 April 2018 - 24 April 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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

Specific details on test material used for the study:

Stability: Stable under storage conditions
Storage conditions: The test material was put into an air-tight container and stored in the test material storage room at room temperature (acceptable range: from 10 °C to 30 °C).

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Cr1: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain rationale: This strain is established as experimental animals and commonly used in the general toxicity study and the testing facility has the historical control data.
- Age at study initiation: Males were seven weeks old, females were nine weeks old.
- Weight at study initiation: 243.7 - 251.8 g (males), 206.0 - 226.3 g (females)
- Housing: Animals were housed individually in stainless steel cages with mesh-floor (260 W x 380 D x 180 H mm).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days
- Method of randomisation in assigning animals to test and control groups: The animals were allocated to groups using simple random sampling six days after the receipt. The animals were identified by painting using a red marker on the tail before the allocation , and by painting using a blue marker on the tail after the allocation. Cages were identified by individual labels and a rack was identified by indicating the study number, sex and dose level.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 25 °C
- Humidity: 40 - 70 %
- Air changes: 10 - 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light per day (light on at 7:00 and off at 19:00).

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: One day before test material application, an area on the back of each test animals, of approximately 5 x 10 cm, was clipped free of fur.
- Type of wrap if used: The dosing formulation was homogeneously applied to a non-woven gauze (5 x 5 cm) that was fixed to the test site by an elastic adhesive bandage.

REMOVAL OF TEST MATERIAL
- Twenty four hours after the application, the non-woven gauze and elastic adhesive bandage were removed and residual test material was removed using purified water and absorbent cotton.

TEST MATERIAL
- Concentration (if solution): test material was suspended in olive oil at a concentration of 20 % (w/v)
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied: 10 mL/kg bw based on the body weight measured on the application day.
- Lot/batch no.: 701019

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: The clinical signs including the mortalities were observed. The animals were observed continuously for 10 minutes after the application, and observed once 30 minutes and three hours after the application, and daily thereafter. The animals were additionally observed after removal of the non woven gauze and elastic adhesive bandage. Body weights were measured at 0 (before application ), 7 and 14 days after the application with an electric balance (SARTORIUS).
- Necropsy of survivors performed: Yes. All animals were subjected to gross necropsy 14 days after the application. Application site, external surface of the body, all orifices, subcutis, cranial, thoracic, abdominal and pelvic cavities with their contents were observed.

Statistics:

Median lethal dose, LD50 value (mg/kg), is estimated according to the number of mortalities and moribundities.

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:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred in any animals at a dose level of 2000 mg/kg bw.

Clinical signs:

other: Slight decreased spontaneous locomotion was observed in four males out of five and all five females between just after the application and three hours after the application. This sign disappeared in all animals one day after the application. Thereafter, n

Gross pathology:

No abnormalities were observed in any animals.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of the study the acute dermal toxicity of the test material to rats was considered to be > 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with the standardised guideline OECD 402, under GLP conditions.

The test material was suspended in olive oil and applied over the dorsal area of Crl:CD(SD) rats after hair of the animals was clipped. The applied area was covered with non woven gauze and elastic adhesive bandage for 24 hours. The dose level was set at 2000 mg/kg bw which is the limited dose in the test method. Five males at seven weeks old and five females at nine weeks old were used for the application. Clinical signs were observed daily for 14 days and body weights were measured 0 (before administration), 7 and 14 days after the administration. The animals were subjected to a gross necropsy 14 days after the administration.
No mortalities or moribundities occurred. No abnormalities associated with the application of the test material were observed in the general clinical observation, body weights measurements or gross necropsy.

Under the conditions of the study the acute dermal toxicity of the test material to rats was therefire considered to be > 2000 mg/kg bw.