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Toxicological information

Respiratory sensitisation

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Administrative data

Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
key 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, well documented, specific investigation of effect of low-level sulfur dioxide exposure on allergic sensitization to inhaled allergen, study acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Repeated exposure to low levels of sulfur dioxide (SO2) enhances the development of ovalbumin-induced asthmatic reactions in guinea pigs.
Author:
Park, J.K. et al.
Year:
2001
Bibliographic source:
Ann Allergy Asthma Immunol 86: 62 - 67.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study meets generally accepted scientific principles, well documented, specific investigation of effect of low-level sulfur dioxide exposure on allergic sensitization to inhaled allergen, study acceptable for assessment.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
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
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): sulfur dioxide

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 250 - 300 g

Test system

Route of induction exposure:
inhalation
Route of challenge exposure:
inhalation
Vehicle:
other: air
Concentration:
Animals of the first and second groups were exposed to 0.1 ppm SO2 for 5 hours a day on 5 consecutive days.
No. of animals per dose:
(A) ovalbumin and sulfur dioxide exposure, N=12, (B) sulfur dioxide exposure, N=12, (C) ovalbumin exposure, N=11,
Controls: (D) saline exposure, N=7
Details on study design:
specific investigation of effect of sulfur dioxide on allergic sensitization to inhaled allergen

ADMINISTRATION/EXPOSURE
- Sulfur dioxide exposure (Groups A and B): 0.1 ppm sulfur dioxide on 5 consecutive days, 5 h/d, in exposure chamber, temperature 20-24 °C, relative humidity 60 %
- Sensitization procedure with ovalbumin (Groups A and C): inhalation of 0.1 % ovalbumin aerosol in exposure chamber for 45 min on day 3, 4 and 5
- Control (Group D): inhalation of phosphate buffered saline (PBS) in exposure chamber for 45 min on day 3, 4 and 5
- Provocation: on day 12 bronchial challenge with (1) PBS for 3 min, (2) 1 % ovalbumin aerosol for 5 min

EXAMINATIONS
- Respiratory function studies:
Measured parameters: airway resistance expressed as enhanced pause (Penh) calculated from the measured parameters expiratory time, relaxation time, peak expiratory flow, peak inspiratory flow
Timepoints of measurement: baseline lung function recorded for 3 min after 10 min acclimatization period; after (1) PBS challenge recorded for 3 min, after (2) ovalbumin challenge recorded for 5, 10, 20, 30, 45 min, 1 hour, 24 hours
- Analysis of bronchoalveolar lavage fluid (BAL): sampling 24 hours after bronchial challenge, determination of numbers of macrophages, lymphocytes, neutrophils, eosinophils
- Histological exmination of bronchial and lung tissue: sections of lung tissue were prepared after BAL sampling (ca. 24 hours after challenge) and examined for epithelial damage and infiltration of inflammatory cells by light microscopy
Challenge controls:
no data
Positive control substance(s):
not specified
Negative control substance(s):
not specified

Results and discussion

Results:
- Respiratory function: significant increase of airway resistance (Penh) only after (A) combined exposure to sulfur dioxide and ovalbumin (p0.05); values for different test groups: (A) OA + SO2, +57.4%, (B) SO2, +10.0%, (C) OA, +14.5%, (D) control (saline), +4.0%

- Analysis of BAL: significant increase of eosinophils only after (A) combined exposure to sulfur dioxide and ovalbumin (p 0.05); values for different test groups: (A) OA + SO2, 10.8%, (B) SO2 4.8%, (C) OA, 2.8%, (D) control (saline), 2.8%

- Histopathologic examination: only after (A) combined exposure to sulfur dioxide and ovalbumin infiltration of inflammatory cells, bronchiolar epithelial damage and mucus and cell plug in the bronchiolar lumen, graded with 2 on a scale of 0-3, grading was 0 for all other groups
Positive control results:
no data
Negative control results:
no data

Applicant's summary and conclusion

Conclusions:
Low level sulfur dioxide exposure to 0.1 ppm for 5 days, 5 hours/day enhanced the development of ovalbumin-induced asthmatic reactions in guinea pigs, as demonstrated by increases of airway resistance, of numbers of eosinophils in bronchoalveolar lavage and by infiltration of inflammatory cells and epithelial damage in bronchial and lung tissue. In contrast sulfur dioxide exposure alone was without effect on any endpoint.