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Toxicological information

Repeated dose toxicity: inhalation

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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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
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 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.