2-(methylamino)ethanol, compound with sulphur dioxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

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

Data source

Reference

Reference Type:

publication

Title:

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

Author:

Takenaka S, Fürst G, Heilmann P, Heini A, Heinzmann U, Karg E, Murray AB, Ruprecht L and Heyder J

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 continuously whole body exposed 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 Disodium disulfite (Na2S2O5) adjusted to pH 7. Three dogs served as control. At the end of the exposure period, the animals were sacrificed and the nasal cavity was prepared for histological examination.

GLP compliance:

no

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

IUPAC Name:

disodium disulphite

Details on test material:

- Name of test material: Sodium metabisulfite (Disodium disulfite)
- Molecular formula: Na2S2O5
- Molecular weight: 190.1 g/mol
- Substance type: technical product
- Physical state: solid, white powder

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 old

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 Disodium disulfite (Na2S2O5) adjusted to pH 7.
- Details on exposure were reported in Karg et al. (1992) and Heyder et al. (1992).

References
- Karg E, Tuch T, Ferron GA, Haider B, Kreyling WG, Peter J, Ruprecht L and Heyder J (1992). Design, operation and performance of whole body chamber for long-term aerosol exposure of large experimental animals. Journal of Aerosol Science 23: 279-290.
- Heyder J, Beck-Speier I, Ferron GA, Heilmann P, Karg E, Kreyling WG, Lenz AC, Maier K, Schulz H, Takenaka S and Tuch T (1992). Early response of the canine respiratory tract following long-term exposure to Sulfur (IV) aerosol at low concentration. I. Rationale, design, methodology, and summary. Inhalation Toxicology 4: 159-174.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

290 days

Frequency of treatment:

Continuous exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mg/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 the exposure period under deep anethesia.

GROSS PATHOLOGY
- Nasal cavity

HISTOPATHOLOGY
- The 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 a graded series of alcohols and embedded in paraplat; deparaffinized sections were stained.

Statistics:

no data

Results and discussion

Results of examinations

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 subepithelial region.

OTHER FINDINGS
- The changes were attributed to the exposure to Metabisulfite 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