Thionyl dichloride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: other: analysis of micronuclei

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented

Data source

Reference

Reference Type:

publication

Title:

Genotoxicity testing of sulfur dioxide (SO2) in a mouse bone marrow micronucleus test complemented with hematological endpoints

Author:

Ziemann C, Hansen T, Pohlmann G, Farrar D, Pohlenz-Michel C, Tillmann T, Mangelsdorf I

Year:

2010

Bibliographic source:

Mutat Res 697, 38-46

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

A bone-marrow micronucleus test according to OECD Guideline No. 474 was performed. NMRI mice (m/f) were exposed by inhalation via wholebody
exposure to 0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or 30 ppm) SO2 for 4 h/day on 7 consecutive days. Animals were sacrificed 24 hafter start of the last exposure, and blood samples (for complementing hematology) and bone marrow smears (for analysis of micronuclei) were prepared.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Sulphur dioxide

EC Number:

231-195-2

EC Name:

Sulphur dioxide

Cas Number:

7446-09-5

Molecular formula:

O2S

IUPAC Name:

oxosulfane oxide

Test material form:

other: gas

Details on test material:

SO2 (CAS 7446-09-5) dilutions in nitrogen (10, 30, 100, and 300 ppm) were supplied and analyzed by AIR LIQUIDE Deutschland GmbH (Spezialgasewerk, Krefeld, Germany). The final exposure atmospheres were generated by mixing a defined flow of the pre-mixed SO2 dilutions in nitrogen to a constant flow of clean air to obtain homogenous exposure atmospheres of 1, 3, 10, and 30ppm (about 2.7, 8, 27 and 80mg/m³

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: gas

Duration of treatment / exposure:

4h/day on 7 consecutive days

Frequency of treatment:

4h/day on 7 consecutive days

Post exposure period:

Animals were sacrificed 24 hafter start of the last exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or 30 ppm) SO2
Basis:
nominal conc.

No. of animals per sex per dose:

6 instead of 5 male and female mice were exposed per SO2-treatment group and per study arm to allow compensation for any exposure-related deaths. However, for the negative (clean air) and positive control (CP) groups the minimal numbers of 5 male and 5 female animals were used in each study arm.

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

Blood samples (for complementing hematology) and bone marrow smears (for analysis of micronuclei) were prepared

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Under the conditions used, exposure to SO2 caused no acute toxicity, mortality, or reduction in body weight. Compared with the clean-air controls, hematological parameters such as hematocrit, hemoglobin, erythrocyte/ platelet/total leukocyte counts, differential white blood cell counts, and indicators of blood formation (reticulocyte counts, ratio of polychromatic to normochromatic erythrocytes in the bone marrow) remained unchanged by SO2 treatment. SO2 did not induce micronuclei in polychromatic erythrocytes of the bone marrow, whereas the positive control cyclophosphamide (60 mg/kg body weight) was quite effective in this respect.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

A bone-marrow micronucleus test according to OECD Guideline No. 474 was performed. NMRI mice (m/f) were exposed by inhalation via wholebody exposure to 0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or 30 ppm) SO2 for 4 h/day on 7 consecutive days. Animals were sacrificed 24 hafter start of the last exposure, and blood samples (for complementing hematology) and bone marrow smears (for analysis of micronuclei) were prepared.

SO2 is thus considered non-genotoxic in polychromatic erythrocytes in the bone marrow of NMRI mice under the conditions and in the concentrations used.