Potassium sulphite

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably well-documented paper on morphologic changes in the nasal cavity.

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:

Morphologic effects of a sulfur (IV) aerosol on the nasal cavity of beagle dogs.

Author:

Takenaka, S.; et al.

Year:

1994

Bibliographic source:

Toxicology Letters, 72, 145-150

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Eight Beagle dogs (35 months of age) were exposed continuously to a metabisulphite aerosol of 1 mg/m3 (equivalent to 0.6 mg/m3 as SO2) for 290 days. The aerosol was generated from an aqueous 3.5% solution of Na2S2O5 adjusted to pH 7. Three dogs served as control.
After sacrifice the nasal cavity was prepared for histological examination.

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:

TEST ANIMALS
- Age at study initiation: 35 months

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:

- The aerosol was generated by nebulization of an aqueous 3.5% solution of Na2S2O5 adjusted to pH 7.
- Details on exposure were reported in "Karg, E. ; et al. (1992): Design, operation and performance of whole body chamber for long-term aerosol exposure of large experimental animals. J. Aerosol. Sci. 23, 279-290" and "Heyder, J.; et al. (1992): Early response of canine respiratory tract following long-term exposure to a sulfur(IV) aerosol at low concentration. I. Rationale, design and summary report. Inhalation Toxicol. 4, 159-174"

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

exposure period: 290 days

Frequency of treatment:

no data

Doses / concentrations

Remarks:

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

No. of animals per sex per dose:

8 animals in total (exposure group)
3 animals in total (control group)

Control animals:

yes

Details on study design:

no data

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

no data

Sacrifice and pathology:

All animals were sacrificed after exposure period under deep anethesia.

GROSS PATHOLOGY: Yes
- Of the nasal cavity only

HISTOPATHOLOGY: Yes
- Th nasal cavity was prepared for histological examination.
- During fixation of the lung the nasal cavity was removed and flushed with fixative via the pharygeal isthmus.
- After complete fixation, the nasal cavity was decalcified with 13 % formic acid.
- Cross sections of the nasal cavity were dehydrated in agraded series of alcohols and embedded in paraplat; deparaffinized sections were stained.

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:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

GROSS PATHOLOGY
- Macroscopic changes were observed in the upper posterior part of the nasal cavity of exposed dogs.
- Focal thickness of the turbinal wall was observed macroscopically.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Histologic changes were observed in the upper posterior part of the nasal cavity of exposed dogs.
- Histological sections showed that the changes were limited to the respiratory mucosa.
- The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a decrease in secretory material, and by a moderate mononuclear cell infiltration in the sub-epithelial region.

OTHER FINDINGS
- The changes have been attributed to the exposure to metabisulphite although the aerosol was contaminated by a low concentration of SO2 (0.18 mg/m3).

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:

Macroscopic and histologic changes were observed in the upper posterior part of the nasal cavity of sulphite exposed animals.