Purine-2(3H),6(1H)-dione

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

Airway inflammation induced by xanthine/xanthine oxidase in guinea pigs

Author:

M. Misawa and H. Arai

Year:

1993

Bibliographic source:

Agent Actions, 38:19-26

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Airway inflammation was assessed by airway vascular permeability in terms of Pontamine skyblue exudation. Vascular permeability was quantified by the extravasation of Pontamine sky-blue dye using a modified method of Evans et al. [T. W. Evans, K. F. Chung, D. F. Rogers and P. J. Barnes, Effect of platelet-activating factor on airway vascular permeability." possible mechanisms. J. Appl. Physiol. 63, 479 484 (1987)]

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Purine-2(3H),6(1H)-dione

EC Number:

200-718-6

EC Name:

Purine-2(3H),6(1H)-dione

Cas Number:

69-89-6

Molecular formula:

C5H4N4O2

IUPAC Name:

xanthine

Specific details on test material used for the study:

Purity: not reported

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Duration of exposure:

5 min

Remarks on duration:

followed by exposure to xanthine oxidase for 5 minutes

Results and discussion

Effect levels

Sex:

male

Remarks on result:

other: hydrogen peroxide and hydroxyl radical converted from superoxide anion caused an intense airway inflammation.

Any other information on results incl. tables

Inhalation of xanthine/xanthine oxidase produced a marked Pontamine sky blue exudation in the trachea, main bronchus and lungs. The xanthine/xanthine oxidase-induced increase in Pontamine sky-blue exudation was attenuated by pretreatment with inhaled catalase, but not by superoxide dismutase. Additionally, in the bronchus and lungs, the increase in Pontamine sky-blue exudation was significantly suppressed by deferoxamine. These results indicate that hydrogen peroxide and hydroxyl radical converted from superoxide anion cause an intense airway inflammation.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The inhalation of xanthine for 5 minutes followed by inhalation of xanthine oxidase for 5 minutes, indicates that hydrogen peroxide and hydroxyl radical converted from superoxide anion cause an intense airway inflammation.

Executive summary:

An investigation was run to see if aerosolized xanthine/xanthine oxidase induces airway inflammation in anesthetized guinea pigs. Inhalation of xanthine for 5 min followed by inhalation of xanthine oxidase for 5 min was performed with an ultrasonic nebulizer in anesthetized animals. Airway inflammation was assessed by airway vascular permeability using Pontamine sky blue. Inhalation of xanthine/xanthine oxidase produced a marked Pontamine sky blue exudation in the trachea, main bronchus and lungs. The xanthine/xanthine oxidase-induced increase in Pontamine sky-blue exudation was attenuated by pretreatment with inhaled catalase, but not by superoxide dismutase. Additionally, in the bronchus and lungs, the increase in Pontamine sky-blue exudation was significantly suppressed by deferoxamine. These results indicate that hydrogen peroxide and hydroxyl radical converted from superoxide anion cause an intense airway inflammation.