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Toxicological information

Genetic toxicity: in vivo

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.