4-amino-N-(4-aminophenyl)benzenesulphonamide

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

Justification for type of information:

Data is from study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

To obtain quantitative animal data in order to assess a possible hazard by inhalation of the product

GLP compliance:

not specified

Test type:

other: Acute Inhalation Toxicity

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-N-(4-aminophenyl)benzenesulphonamide

EC Number:

240-834-4

EC Name:

4-amino-N-(4-aminophenyl)benzenesulphonamide

Cas Number:

16803-97-7

Molecular formula:

C12H13N3O2S

IUPAC Name:

4-amino-N-(4-aminophenyl)benzenesulphonamide

Details on test material:

Name - 4-amino-N-(4-aminophenyl)benzenesulphonamide
InChI - 1S/C12H13N3O2S/c13-9-1-3-10(4-2-9)15-11-5-7-12(8-6-11)18(14,16)17/h1-8,15H,13H2,(H2,14,16,17)
Smiles - O=S(=O)(c1ccc(cc1)Nc1ccc(cc1)N)N
Mol. formula: C12H13N3O2S
Molecular Weight - 263.32 g/mole

Specific details on test material used for the study:

Name - 4-amino-N-(4-aminophenyl)benzenesulphonamide
InChI - 1S/C12H13N3O2S/c13-9-1-3-10
(4-2-9)15-11-5-7-12(8-6-11)18(14,16)17/h1-8,15H,13H2,(H2,14,16,17)
Smiles - O=S(=O)(c1ccc(cc1)Nc1ccc(cc1)N)N
Mol. formula: C12H13N3O2S
Molecular Weight - 263.32 g/mole
Purity - approx. 98% (dry substance)
Physical state /appearance : crystalline powder/brown
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 8/86
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions:Stability was ensured for 2 years under normal conditions

Test animals

Species:

rat

Strain:

other: SPF Wistar/Chbb :THOM

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr . K . Thomae GmbH, D-7950 Biberach, FRG
- Age at study initiation: approx . 8- 9 weeks
- Weight at study initiation: male - 277 ± 4 .6 g, female - 191 ± 6.8 g
- Fasting period before study:
- Housing:housed in groups of five in cages type D III of Becker, without bedding
- Diet (e.g. ad libitum): KLIBA rat/mouse laboratory diet A 343 10 mm pellets,ad libitum
- Water (e.g. ad libitum):drinking water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): range of 20-24°C
- Humidity (%): range of 30-709%
- Air changes (per hr): central air-conditioning system
- Photoperiod (hrs dark / hrs light): light/dark rhythm of 12 hours.
IN-LIFE DATES: From:Aug 19, 1986 to Sept 2, 1986.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

6.1 µm

Geometric standard deviation (GSD):

2

Remark on MMAD/GSD:

No data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:glass-steel construction
- Exposure chamber volume: volume V~ 551
- Method of holding animals in test chamber:The animals were restrained in tubes and their snouts projected into the inhalation chamber.
- Source and rate of air: A dust aerosol was generated by means of a vibration dust
partitioning equipment
- Method of conditioning air:The supply air was conditioned via a central air-conditioning
system in such a way that there was a temperature of 19 - 25°C in the exposure apparatus.
- System of generating particulates/aerosols: Vacuum compressed air pump (Millipore) XX 60 220 5 0
- Method of particle size determination: Andersen Stack Sampler Mark II I

TEST ATMOSPHERE
- Brief description of analytical method used: The preweighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drawn through the filter. The dust concentration in mg/1 was calculated from the difference between the preweight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmosphere .

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

No data

Concentrations:

5.2 mg/L

No. of animals per sex per dose:

Total = 10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period . A check for dead animals was made daily.
- Necropsy of survivors performed: yes
- Other examinations performed: Animals were observed for clinical signs, body weight,organ weights, histopathology examinations.

Statistics:

The statistical evaluation of the concentration/effect relationship was carried out on the basis of the binomial test (Wittig, H . : Mathematische Statistik 1974, pp . 32 -35) in accordance with tables of the BASF Computer Center.

Results and discussion

Preliminary study:

No data

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at 5.2 mg/L air.

Clinical signs:

other: During and after exposure, animals were accelerated to irregular breathing; and as of day 1 of the observation period, no abnormalities were detected in the animals of the test group.

Body weight:

The body weight gain of male and female rats was observed.

Gross pathology:

No abnormalities detected in male and female rats.

Other findings:

No data

Any other information on results incl. tables

Table – 1. Concentration and lethality

The mean of the concentration in the test group and the lethality rates (number of animals that died / number of animals exposed) are presented in the following table –

Cumulated lethality on day	Test group (concentration ) 1 (5 .2 mg/1 )
	M	F
0	0/5	0/5
1	-	-
2	-	-
7	-	-
14	-	-
Total at end of the study	0/10

 

m = male, f = femal e

- = lethality unchanged

0 = day of exposure

 

Table – 2. Body weight

Mean body weight	Before the study		After 7 days		After 14 days
	Male	Female	Male	Female	Male	Female
Test group 1 weight in gm number of animals	277   5	191   5	296   5	198   5	321   5	208   5
Historical (air) control Weight in gm	248	177	285	196	317	210

 

The body weight gain of male and female rats in the test group 1, compared with a historical control collective, was not affected by the substance over the total observation period. 

 

Table – 3. Results of analytical measurements - Concentration measurements

Test group 1

Sample No	Analyt . concentration mg/L
1	4.63
2	5.12
3	4.82
4	5.34
5	5.59
6	5.40
7	4.86
8	5.55
Mean	5.2
Standard deviation of the mean	± 0.36
Nominal concentration	47. 5

 

Table – 4. The particle size analysis of the test group led to the following results:

Stage	EACD 50% (µm)	mg	Percentage distribution	Cumulative distribution in %
Pre-impactor	26.6	42.1
Cascade impactor
0	29.5	0.06	1.6	98.4
1	18.2	0.09	2.3	96.1
3	8.5	0.99	25.6	70.5
4	5.5	1.25	32.4	38.1
5	2.8	1.07	27.7	10.4
7	1.2	0.35	9.1	1.3
Backup filter	< 1.2	0.05	1.3
Σ = 3.86			100	-

 

	mass (mg)
Pre-impactor Cascade impactor wall losses	42. 1 3. 86 30. 4

 

The MMAD 50% = 6 .1 um

(Geometrical standard deviation = 2 .0) was calculated from the results of the particle size analysis.

A respirable dust fraction that might reach the alveoli of 70.5 % was obtained from the results of the particle size analysis.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute inhalation toxicity study in Wistar male/female rat by using 4-amino-N-(4-aminophenyl)benzenesulphonamide (16803-97-7) for exposure of 4 hr was considered to be >5.2 mg/L air.

Executive summary:

The acute inhalation toxicity study was conducted based on the OECD Guidelines, method 403 on 4-amino-N-(4-aminophenyl)benzenesulphonamide (16803-97-7) in Wistar male/female rat at the concentration of 5.2 mg/L air. 5 male and 5 female rats were used for the test group.Head-nose inhalation system INA 20 (glass-steel construction, BASF Aktiengesellschaft, volume V  ̴ 55 1) the animals were restrained in tubes and their snouts projected into the inhalation chamber.A dust aerosol was generated by means of a vibration dust partitioning equipment. The supply air was conditioned via a central air-conditioning system in such a way that there was a temperature of 19 - 25°C in the exposure apparatus.The inhalation mixture was offered to the animals for inhalation for 4 hours.8y means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). The nominal concentration was calculated from the amount of substance consumed and the air flow. 30 minutes after the beginning of the test at the earliest, one sample was taken from the test group for the particle size analysis. After the exposure period the animals were observed for 14 days. The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.Animals were observed for clinical signs, body weight, organ weights, histopathology examinations. The statistical evaluation of the concentration/effect relationship was carried out on the basis of the binomial test (Wittig, H. : Mathematische Statistik 1974, pp . 32 -35) in accordance with tables of the BASF Computer Center. No mortality was observed at 5.2 mg/L air. During and after exposure, animals were accelerated to irregular breathing; and as of day 1 of the observation period, no abnormalities were detected in the animals of the test group. The body weight gain of male and female rats was observed.No abnormalities detected in male and female rats. Therefore, LC50 was considered to be>5.2 mg/L air,when Wistar male/female rat was treated with 4-amino-N-(4-aminophenyl)benzenesulphonamide by inhalation for 4 hours.