Disodium disulphite

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well-documented short communication on changes in the clearing mechanism due to sulphite exposure.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Long-term exposure of dogs to a sulphite aerosol.

Author:

Ferron, G.A.; et al.

Year:

1990

Bibliographic source:

J. Aerosol Sci. 21, S479-S482

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Eight Beagle dogs were exposed in chambers to an aerosol concentration of 1 mg/m3 Na2S2O5 or 290 days. Prior to this exposure the animals were housed in chambers under clean air conditions for 320 days. Selected parameters of lung clearance, biochemistry, cytology, and morphology were determined during both periods to find sensitive parameters for early changes of lung function. Only changes of lung clearance parameters are described in this paper.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium disulphite

EC Number:

231-673-0

EC Name:

Disodium disulphite

Cas Number:

7681-57-4

Molecular formula:

Na2S2O5

IUPAC Name:

disodium disulphite

Details on test material:

- Name of test material (as cited in study report): sodium metabisulfite
- Molecular formula (if other than submission substance): Na2S2O5
- Molecular weight (if other than submission substance): 190.1 g/mol
- Substance type: technical product
- Physical state: solid, white powder
No further details are given.

Test animals

Species:

dog

Strain:

Beagle

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

Inhalation conditions are reported in Tuch, T.; et al. (1990): Long-term exposure of dogs to a sulphite aerosol: I. Rationale and design parameters. J. Aerosol Sci. 21.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

320 days exposure to clean air (control period) followed by 290 days exposure to Na2S2O5 aerosol (exposure period)

Frequency of treatment:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
1mg Na2S2O5 /m3
Basis:
nominal conc.

No. of animals per sex per dose:

8 dogs in total

Control animals:

other: dogs served as their own conrol

Details on study design:

no data

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: No data

FOOD CONSUMPTION: No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER:
- Samples of urine and faeces were collected from each dog in 2-week intervals and analyzed for 57Co and 60Co.
- The particulate fraction of 60Co-FAP in faecal samples was distinguished from the non-particulate 60Co in order to determine directly mechanical particle transport from the lungs to the gut.

Sacrifice and pathology:

no data

Other examinations:

- Selected parameters of lung clearance, biochemistry, cytology, and morphology were determined during both periods to find sensitive parameters for early changes of lung function.
- Only changes of lung clearance parameters are described in this paper (other results are given by "Maier, K.L; et al. (1990). Long-term exposure of dogs to sulphite aerosol: II. Effect on biochemical and cellular lung parameters. J. Aerosol. Sci.21" and "Takenaka, S.P.; et al. (1990). Long-term exposure of dogs to sulphite aerosol: IV. Effects on airway morphometry. J. Aerosol. Sci. 21." ):
- Lung clearance was tested with moderately soluble (57Co3O4) and insoluble aerosol particles (fused aluminosilicate (FAP) tracered with 60Co) after a single inhalation.

Statistics:

no data

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

OTHER FINDINGS
- Three out of eight dogs showed significant changes in clearance rate of moderately soluble particles during the sulphite exposure compared to the clearance rate during clean air exposure.
- These changes were confirmed by in vitro clearance measurements in alveolar macrophages.
- First indications were found for changes in the mechanical particle transport rates during sulphite exposure.

Effect levels

Dose descriptor:

NOAEC

Remarks on result:

not determinable

Remarks:

no NOAEC identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Only changes of lung clearance parameters are described in this paper. Three out of eight dogs showed significant changes in clearance rate of moderately soluble particles during the sulphite exposure compared to the clearance rate during clean air exposure.