N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

September 07, 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea

EC Number:

876-151-9

Cas Number:

2292123-68-1

Molecular formula:

C27H24N2O7S2

IUPAC Name:

N,N’-di[3-(p-toluene sulfonyl)oxy]phenyl urea

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house Laboratory
- Females nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable): not specified
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: Male (min. 262.7g, max. 269.3g); Female (min. 181.3g, max. 191.2g)
- Fasting period before study: not applicable
- Housing: 3 rats/cage (polypropylene cages covered with stainless steel grip tops
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 56 60 66
- Air changes (per hr): minimum 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.17 µm

Geometric standard deviation (GSD):

2.61

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only inhalation equipment
- Exposure chamber volume: 2.062 Litres
- Method of holding animals in test chamber:
- Source and rate of air (airflow): dynamic air flow rate of 523 to 524 air changes per hour, ensuring adequate oxygen content of at least 19%. Co2 level was less than 1%.
- System of generating particulates/aerosols: The test item was loaded in a cylindrical powder reservoir which was loaded onto the dust generation system positioned below the cylindrical brush. The transportation piston pushes the compacted mass at a given speed out of the reservoir and onto the rotating brush which carries it into the upper part of the dispersion head. The mass is blown out of the brush by a high velocity air stream and is carried off via the dust exit nozzle to the chamber. The air flow rate through the dust generator was maintained at approx. 18 litres per minute.
- Method of particle size determination: gravimetric analysis
- Temperature, humidity in air chamber: 21.2 to 22.4°C, 52.0 to 53.7%,

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: gravimetric samples were collected and analysed to determine the chamber aerosol concentration. The concentration of the aerosol present in the chamber was determined gravimetrically twice during the 4 hour exposure period. Each sample was taken by drawing chamber atmosphere from the animal breathing zone at a set rate using a constant flow air sampling pump (0.8 LPM)
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analysis

Duration of exposure:

4 h

Remarks on duration:

As stated in the test guideline

Concentrations:

1.819 mg/L air (Maximum Achievable Breathing Zone Concentration) equivalent to 34.052 mg/L air (nominal)

No. of animals per sex per dose:

3 male/3 female per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats observed twice per day for morbidity and mortality, once per day for clinical signs. Body weights recorded at Day 0 and post-exposure Day 1, 3, 7 and 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: gross pathology, external examination and the opening of the nasal passage, abdominal and thoracic cavities

Statistics:

Not applicable.

Results and discussion

Preliminary study:

Conducted without animals to determine the maximum concentration of the test item which could be generated in the test system. Breathing zone concentration ca. 1.8 mg/L air. Same experimental conditions used for main study.

Effect levels

Sex:

male/female

Dose descriptor:

LC50 cut-off

Effect level:

> 1.819 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

No mortality was recorded at the highest concentration tested.

Mortality:

None.

Clinical signs:

other: None

Body weight:

A decrease in the mean body weight was observed on Day 1 whereas an increase in the mean body weight was observed on Day 3, 7 and 14 in both sexes when compared with the Day 0 mean body weight. See Table 1 below.

Gross pathology:

External: no abnormalities
Internal: no lesions
No treatment related effects.

Any other information on results incl. tables

Table 1: Individual and mean body weights (g) and body weight changes (%)

 

Maximum Achievable Breathing Zone Concentration (mg/L air)	Sex	Rat no.	Body weights (g) on Day					Percent body weight change on Day
			0	1	3	7	14	1	3	7	14
1.819	Male	1	265.8	263.1	279.1	302.9	330.0	-1.0	5.0	14.0	24.2
		2	262.7	260.4	275.2	294.3	320.2	-0.9	4.8	12.0	21.9
		3	269.3	267.8	280.8	300.2	330.4	-0.6	4.3	11.5	22.7
		Mean	265.9	263.8	278.4	299.1	326.9	-0.8	4.7	12.5	22.9
		Standard Deviation	3.3	3.7	2.9	4.4	5.8	0.2	0.4	1.3	1.2
	Female	4	181.5	180.1	190.7	198.0	211.3	-0.8	5.1	9.1	16.4
		5	181.3	180.2	184.5	195.5	213.1	-0.6	1.8	7.8	17.5
		6	191.2	189.2	200.8	208.8	219.9	-1.0	5.0	9.2	15.0
		Mean	184.7	183.2	192.0	200.8	214.8	-0.8	4.0	8.7	16.3
		Standard Deviation	5.7	5.2	8.2	7.1	4.5	0.2	1.9	0.8	1.3

Key: 0 = before exposure

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

The test item concentration was tested at the maximum achievable breathing zone concentration and no mortality was observed and hence no LC50 could be calculated.

Conclusions:

The 4 hour acute median lethal concentration (LC50) of the test item in male and female Wistar was found to be greater than the maximum achievable breathing zone concentration of 1.819 mg/L air.