Registration Dossier

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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.