Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1981-10-22 to 1981-11-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
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.
Justification for type of information:
Read-across
The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pH value which is clearly described in published literature and summarised in the following equations:[1],[2]
SO2 + H2O <->`H2SO3´ H2SO3<->H+ + HSO3- <-> 2H+ +SO32- 2HSO3- <->H2O +S2O52 –
As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all compounds are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites. Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II) so that this substance can also be added to the read-across concept.[2],[1]
It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.
2 S2O42-+ H2O→2HSO3-+ S2O32 -

All sulfite, hydrogensulfite and metabisulfite substances are highly soluble in water, establishing upon dissolution an equilibrium that depends on solution pH as follows: ,

1. SO2 + H2O <-> H2SO3
2. H2SO3 <-> H+ + HSO3- <-> 2H+ + SO32-
3. 2 HSO3- <-> H2O + S2O52-

Under oxidising conditions, e.g., in surface waters, sulfite is oxidized to sulfate catalytically by (air) oxygen or by microbial action. A half-life of 77 hour was measured in deionized water, already suggesting substantial abiotic degradation. However, the presence of metal cations in the environment, such as copper, iron and manganese, accelerates the oxidation rate. In soils, HSO3- and SO32- ions are unstable and quickly oxidise. Further, because of the instability of SO32-, metal sulfites are generally too soluble to persist in soils. Thus, the most stable and predominant sulfur form in freshwater and in all but highly reduced environments is sulfate (SO42-). In highly reduced soils and sediments, sulfites may be reduced to sulfides (Lindsay, 1979; OECD SIDS, 2012).

Only the properties of the sulfite anion are considered relevant determinants of environmental toxicity since respective cations, i.e. ammonium, calcium, magnesium, sodium and potassium, are not assumed to contribute substantially to differences therein. Sulfite, although naturally present in the environment and also a metabolite and intermediate of sulfur-containing amino acids in organisms, may have an impact on the environment at elevated levels. Sulfites do not bioaccumulate.

In sum, unrestricted read-across between the sulfites, hydrogensulfites and metabisulfites is justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
, see "Rationale for reliability"
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- 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

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 55 ± 5%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
other: inhalation: dust/aerosol test
Type of inhalation exposure:
nose/head only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
3 µm
Geometric standard deviation (GSD):
2.7
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- 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.

TEST ATMOSPHERE
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

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 3.0 µm (GSD: 2.7 µm)
- Respirable dust: 90.7 %
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric determination
Duration of exposure:
4 h
Concentrations:
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:
yes
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.
Statistics:
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
Sex:
male
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Statistical certainty: 99.9%
Sex:
male/female
Dose descriptor:
LC50
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.
Mortality:
No mortality occurred.
Clinical signs:
other: 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:
GHS criteria not met
Conclusions:
LC50 (male and female rats; 4 hours) > 5.5 mg/L (actual concentration)
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.