Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Reinhardt, 1971, 1973 "Cardiac arrhythmias and aerosol sniffing" Arch. of Environ. Health, vol 22, pp 265-269; Epinephrine induced cardiac arrhythimia poetential of some common industrial solvents, Journal of Occupational Medicine, vol 15, pp 953-955
Deviations:
no
Principles of method if other than guideline:
The cardiac sensitisation potential of the test article was examined utilizing six beagle dogs. Adrenaline was administered intravenously before and during inhalation of the test substance. The effect of adrenaline on the ECG was compared. Positive evidence of cardiac sensitisation was taken as the presence of multiple multifocal ectopic beats following adrenaline administration during gas inhalation with little or no response to the same adrenaline dose in the absence of the test substance.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report: T-5452
- Substance type: Liquid
- Physical state: Liquid
- Analytical purity: >98%
- Lot/batch no.: 102
- Storage condition of test material: Stored at ambient (outdoor) temperature or at room temperature during the period of the study.

Results and discussion

Any other information on results incl. tables

- Sex: male

- Endpoint: EC50

- Effect level: >23

- Unit of dose: %

- Remarks: No cardiac effcts noted at the highest exposure concentration

- Mortality: none

- Clinical signs: No data

- Body weight and weight gain: No data

- Gross pathology: NA

Applicant's summary and conclusion

Conclusions:
Cardiac sensitization EC50 > 23%.
Executive summary:

This study was designed to assess the cardiac sensitization potential of the test article in beagle dogs. Adrenaline was administered by intravenous injection before and during inhalation of the test article. The effect of the adrenaline on the ECG pattern was examined. Positive evidence of cardiac sensitization would be observed as the presence of multiple multifocal ectopic beats or ventricular fibrillation following adrenaline administration during inhalation of the test substance. No such effect should be observed in the absence of the test article. The test article was administered at concentrations of 0 (control), 5, 10, 20, and 23% v/v in air. No signs of cardiac sensitization were observed in any dogs at any dose level. The results of the study show that the test article is without potential to cause cardiac sensitization in dogs at 23% v/v, the maximum attainable concentration in air.