Registration Dossier

Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981-10-22 to 1981-11-05
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Comparable to guideline study reliable with restrictions Minor deviations without an effect on the results: - According to the guideline, the air flow, humidity and temperature should be measured, which was not done in this study. It is considered as important to state the humidity, since humidity could have an influence on the substance administration. - There was no statement about an acclimatisation period, which according to the guideline shoud be at least five days. - It was not stated, if the exposure period was conducted after a period of equilibration of the chamber concentration. According to the guideline, the 4 hour exposure period should start after the equilibration of the chamber concentration. - It was not explicitly stated if the respiratory tract was investigated during the pathological examination. According to the guideline consideration should be given to performing a gross necropsy of animals where indicated by the nature of the toxic effects observed with particular reference to any changes in the respiratory tract. - According to the guideline, it should be stated how the exhausted air was treated, which was not stated in this report.

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
equivalent or similar to
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
,adopted 1981-05-12
, see "Rationale for reliability"
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Details on test material:
- Name of test material (as cited in study report): Natriumsulfit wasserfrei Z
- Chemcial description: Sodium sulphite
- Molecular formula: Na2SO3
- Physical state: Solid, colourless powder
- Lot No.: 81/311
- Analytical purity: 93%
- Expiration date: At least 2 years under normal storage conditions
No further information on the test material was stated.

Test animals

Details on test animals and environmental conditions:
- Source: WIGA Versuchstierzuchtanstalt, Sulzfeld,
- Age at study initiation: ca. 8 - 10 weeks
- Weight at study initiation: Mean body weight males (test group): 303 +/- 18 g; Mean body weight females (test group): 234 +/- 12 g; Mean body weight males (control group): 307 g; Mean body weight females (control group): 235 g
- Housing: They were housed in groups of five in cages of Becker, type D III, without bedding. The animals were accommodated in fully air-conditioned rooms.
- Diet (ad libitum): SSNIFF R complete diet for rats and mice, manufacturer: SSNIFF-Versuchstierdiaeten GmbH, Soest, FRG
- Water (ad libitum): Tap water

- Temperature: 22 +/- 2°C
- Humidity: 55 +/- 5%
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
other: inhalation: dust/aerosol test
Type of inhalation exposure:
nose/head only
Details on inhalation exposure:
- Exposure apparatus: Head-nose inhalation system INA 20 (glass/steel construction, BASF Aktiengesellschaft, V ~ 55 l); The animals are restrained in tubes and their snouts project into the inhalation chamber.

- System of generating particulates/aerosols: A mixture of dust and air was generated by means of a vibration aerosol generator. By means of a dust generator the substance to be tested was generated into a dust aerosol, which was passed into the inhalation system. The concentration was adjusted by varying the amplitude and frequency of the vibrator. The rate of flow was adjusted as follows: 1500 l/h of compressed air through the vibrator.By means of an exhaust air system the pressure ratios in the inhalation chamber were adjusted in such a way that the amount of fresh air was about 10% higher (excess pressure). This ensured that the mixture of test substance and air was not diluted by laboratory air in the breathing zones of the animals.

- Method of particle size determination:
Tools used: Andersen Stack Sampler Mark III Millipore vacuum-compressed air pump XX 60 220 50, nozzle with limited streaming 3l/min, Millipore sampler, inner diameter 6.9 mm, BASF-manometer, stop watch.
Sampling: At the earliest 30 minutes after starting the inhalation exposure 1 sample was drawn (test group).
The impactor was equipped with a glass-fiber collecting plate and a particle filter. The impactor was connected with the pump and the exposure apparatus and a sample of (9 l) was extracted.
The impacotr was disassembled, the collecting plate and particle filter were weighed.
The content of the pre-impactor was determined gravimetrically.

Tools used:
- Vacuum-compressed air pump (Millipore) XX 60 220 50
- Filtration apparatus with testing probe (Millipore) (Inner diameter: 4 mm)
- Filter: MN 85/90 Bf (d= 4.7 cm)
- Ballance: Cahn 26
Sample drawing:
- Speed of sampling: 1.25 m/s
- Amount of sampling: 1 l
- Position of sampling: close to the animals' nose
- Diameter of testing probe: 4mm
- Frequency of sampling: 1 sample every 30 minutes

- Brief description of analytical method used: Gravimetric determination of the concentration; The preweighted filter was placed in the filtration apparatus. A limited volume of the dust-aerosol was drawn by means of a vacuum-compressed air pump through the filter. The dust concentration was calculated be taking the difference between the preweighted filter and the filter weighed after sampling.
- Samples taken from breathing zone: Yes

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 3.0 µm (GSD: 2.7 µm)
- Respirable dust: 90.7 %
No further information on the inhalation exposure was stated.
Analytical verification of test atmosphere concentrations:
gravimetric determination
Duration of exposure:
4 h
5.5 +/- 0.29 mg/l (actual concentration)
Nominal concentration: 27.9 mg/l
No. of animals per sex per dose:
10 males / 10 females (test group)
10 males / 10 females (control group)
Control animals:
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 symptoms were recorded each workday. Mortalities were recorded each day.
- Necropsy of survivors performed: Yes, at the end of the 14-day observation period the animals were sacrificed by CO2 and were subjected to a gross-pathological examination.
No further infromation on the study design was stated.
The statistical evaluation of the concentration-response relationship was carried out in accordance with the binominal test (Wittig, H.: Mathematische Statistik 1974, pp. 32 - 35) according to tables of the BASF Computer Center.
The particle size was determined in the Department of Toxicology of BASF Aktiengesellschaft in accordance with mathematical and graphical methods of evaluating particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, pp. 235-259).

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Dose descriptor:
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Dose descriptor:
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Statistical certainty: 99.9%
Dose descriptor:
Effect level:
> 22 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Remarks on result:
other: Recalculated by using the Haber-Rule C X t = k.
No mortality occurred.
Clinical signs:
During exposure nothing abnormal was detected.
After exposure: substance-contaminated heads, and unstable, staggering gait. After one day nothing abnormal was detected.
Body weight:
The development of the body weight of the males of test group was decelerated compared to the control animals.
The females of the test group showed no notable difference in body weight compared to the females of the control group.
Gross pathology:
Sacrificed animals: Nothing abnormal was detected.
Other findings:
No data

Any other information on results incl. tables

Mean body weights:

   before start of the study     after 7 days     after 14 days   
   male rats  female rats  male rats  female rats  male rats  female rats
 Group 1  10 animals  10 animals  10 animals  10 animals  10 animals  10 animals
 Weight in g  303  234  329  248  351  251
 Control  10 animals  10 animals  10 animals  10 animals  10 animals  10 animals
 Weight in g  307  235  344  240  372  250

Applicant's summary and conclusion

Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: EU
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.