Sulphur dioxide

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo

Remarks:

Type of genotoxicity: other: gene toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Entry adopted from the OECD SIAR on sulfur dioxide without modification.Study meets generally accepted scientific principles, study sufficiently documented; specific investigation of effect of sulfur dioxide exposure on induction of DNA single strand breaks by N-nitrosamines; study acceptable for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies

Author:

Pool, B.L.; et al.

Year:

1988

Bibliographic source:

Carcinogenesis 9: 1247-1252

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study meets generally accepted scientific principles, study sufficiently documented; specific investigation of effect of sulfur dioxide exposure on induction of DNA single strand breaks by N-nitrosamines; study acceptable for assessment.

GLP compliance:

not specified

Type of assay:

other: DNA single strand break

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:

SO2

IUPAC Name:

Sulphur dioxide generated from sulphur by combustion

Details on test material:

- Name of test material (as cited in study report): sulfur dioxide
- Analytical purity: 99.975%
No further details are given.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4 months
- Housing: rats were housed under standard conditions, two animals per cage
- Diet: Altromine pellets
- Water: ad libitum
No further details are given.

Administration / exposure

Route of administration:

inhalation

Vehicle:

air

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: The SO2 gas was mixed with fresh air by a dynamic gas diluter. The gas exchange rate was 10 vol/hour. The gas concentration in the chamber was continuously monitored.
No further details are given.

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

continuously

Post exposure period:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
50 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

Groups of 5 animals each were exposed to SO2 or NOx or air.

Control animals:

yes

Positive control(s):

no data

Examinations

Tissues and cell types examined:

Primary cells: Liver and lung cells were isolated from rats anesthetised with Nembutal for liver and chloraldehydrate for lung. Immediately after isolation, the viability of liver and lung cells was determined with the trypan blue exclusion assay.

Details of tissue and slide preparation:

Determination of genotoxic properties: Genotoxic properties induced by the nitrosamines were determined as DNA single strand breaks. Suspensions (1 ml) of rats hepatocytes were treated with nitrosamines and incubated in a shaking water bath at 37°C for 1 hour. After determination of viability, the cells were loaded onto polycarbonate filters for fractionated DNA elution.

Evaluation criteria:

As an evaluation of genotoxicity, the total amount of DNA retained on the filters of the treated cells was substracted from the percentage DNA retained in the controls.

Statistics:

no data

Results and discussion

Test results

Sex:

female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not examined

Negative controls validity:

not examined

Positive controls validity:

not examined

Additional information on results:

The induction of DNA single strand breaks by three nitrosamines (N-nitroso-acetoxymethylmethylamine, N-nitrossodimethylamine and N-nitrosomethylbenzylamine) was decreased in hepatocytes from SO2-treated animals.

Any other information on results incl. tables

- Genotoxic activity: no induction of DNA single strand breaks by sulfur dioxide alone; sulfur dioxide pretreatment decreased the genotoxic activity of the nitrosamines.
- Cell viability of hepatocytes and lung cells was not affected by the sulfur dioxide exposure.
- Leakage of enzymes: LDH activity decreased in hepatocytes
- Enzyme activity in serum: LDH activity increased
- Activities of foreign compound metabolizing enzymes: NDMA-D increased in hepatocytes and GST decreased in lung cells

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Pretreatment of rats by a 2-week continuous exposure to 50 ppm sulfur dioxide reduced the rate of DNA single-strand breaks induced by N-nitrosamines in vitro in isolated cultured hepatocytes. The sulfur dioxide exposure did not affect cell viability of isolated liver or lung cells. The activity of LDH was increased in the serum of the treated rats whereas this enzyme activity was strongly impaired in isolated hepatocytes. Activities of foreign compound metabolizing enzymes were changed with an increase of NMDA-D in hepatocytes and a decrease of GST in lung cells.