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Endpoint summary

Description of key information

In an acute oral toxicity study (OECD TG 423) with N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)-benzenesulfonamide, no mortality was observed. The LD50 can be considered to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020-05-14 to 2020-09-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name: N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)benzenesulfonamide
- Lot/batch no.: 2019001
- Purity: 98.78%
- Appearance/physical state: white crystalline powder
- Expiry Date: 2020-10-28
- Storage: at room temperature, protected from light


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- The test item was suspended with aqua ad injectionem. The decision on the vehicle was made based on the solubility test. The formulation was used within 1 hours after adding the vehicle to the test item and was kept under magnetic stirring during the daily administration.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 – 9 weeks
- Weight at study initiation: Step 1: 128 – 140 g; Step 2: 156 – 164 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Historical data:
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days under laboratory conditions
- Microbiological status: The animals were derived from a controlled full-barrier maintained breeding system (SPF).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
- Step 1: From: 19 May 2020 To: 02 June 2020
- Step 2: From: 26 May 2020 To: 09 June 2020

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 1.3-1.6 mL (corresponding to 10 mL/kg body weight)
- Justification for choice of vehicle: The decision on the vehicle was made based on the solubility test and its non-toxic characteristics
- Lot/batch no. (if required): Deltamedica, lot no. 901110, expiry date: 12/2021
- Purity: ad injectionem

MAXIMUM DOSE VOLUME APPLIED: 1.6 mL

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 400 mg/kg bw.
- Clinical signs including body weight: Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

Results were interpreted according to OECD Guideline 423, Annex 2 and GHS.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item showed no mortality.

Clinical signs:

other: The most relevant clinical findings in the animals were reduced spontaneous activity and apathy starting shortly after test item administration. All animals recovered within 4 hours post-dose.

Body weight:

other body weight observations

Remarks:

no effects on body weight throughout the 14-day observation period.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Table 1: Absolute Body Weights in g and Body Weight Change in %

Step	Animal No. / Sex	Starting Dose (mg/kg bw)	BW (g)			Body Weight Change in Comparison to Day 1 (%)
			Day 1	Day 8	Day 15	Day 15
1	1 / Female	2000	128	160	165	+29
	1 / Female		140	175	185	+32
	1 / Female		136	166	186	+37
2	2 / Female	2000	156	177	185	+19
	2 / Female		162	189	195	+20
	2 / Female		164	191	202	+23

 

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study conducted according to OECD TG 423 (acute toxic class method), the test item did not induce mortality at the limit dose of 2000 mg/kg bw. The LD50 is therefore considered to be >2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (OECD TG 423, acute toxic class method), groups of 3 fasted female Crl:WI (Han) rats (8-9 weeks of age), were given a single dose of 2000 mg/kg bw N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)-benzenesulfonamide (purity 98.78%) in water via oral gavage. Animals were then observed for 14 days.

There was no mortality observed. Transient slight, unspecific signs of toxicity including reduced spontaneous activity and apathy were observed shortly after test item administration. All animals recovered within 4 hours post-dose.

Based on the results, the oral LD50 is considered to be greater than 2000 mg/kg bw and no clssification for acute oral toxicity is warranted according to CLP Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study (OECD TG 423, acute toxic class method), groups of 3 fasted female Crl:WI (Han) rats (8-9 weeks of age), were given a single dose of 2000 mg/kg bw N-(4-((4-(3-phenylureido)phenyl)sulfonyl)phenyl)-benzenesulfonamide (purity 98.78%) in water via oral gavage. Animals were then observed for 14 days.

There was no mortality observed. Transient slight, unspecific signs of toxicity including reduced spontaneous activity and apathy were observed shortly after test item administration. All animals recovered within 4 hours post-dose.

Based on the results, the oral LD50 is considered to be greater than 2000 mg/kg bw and no clssification for acute oral toxicity is warranted according to CLP Regulation 1272/2008.

Justification for classification or non-classification

Based on the available results, classification for acute oral toxicity according to CLP Regulation 1272/2008 is not warranted.