Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Non-GLP, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment, original source is not available.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Unnamed
Year:
1978
Report Date:
1978
Reference Type:
secondary source
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
other: emetic effects
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Twelve healthy volunteers were orally dosed with 0.25, 0.5, 1.0, 2, 3, 4, and 8 mg. The emetic effects of the substance were studied. Based on the obtained results further studies were performed with a maximum dose of 2 mg.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 12
- Demographic information: average weight 70 kg.
Ethical approval:
not specified
Route of exposure:
oral
Reason of exposure:
intentional
Details on exposure:
12 healthy volunteers were orally exposed to the test substance. Doses of 0.25 (n=1), 0.5 (n=1), 1.0 (n=2), 2 (n=3), 3 (n=2), 4 (n=2), and 8 (n=1) mg were given in tablet form. Based on the obtained results further studies were performed with a maximum dose of 2 mg.
Examinations:
The emetic effects of the substance were studied and blood levels of two volunteers were measured.

Results and discussion

Clinical signs:
The volunteer given 8 mg vomited as did the one given 4 mg. Nausea was a marked effect reported by almost all of the volunteers. The substance was tolerated poorly at doses above 1 - 2 mg. Nausea, vomiting, dissiness, sweating and flushing were complained of. Further studies performed with a maximum dose of 2 mg. Of those who took 2 mg, approximately 10% vomited and 60% complained of nausea.

See any other information on results incl. tables for an overview of the emetic action.
Results of examinations:
It can be seen that when the blood levels of the test substance in the 2 volunteers given 4 mg are compared, the one that vomited absorbed the compound more quickly than the other. Blood concentrations of one volunteer were 0.081, 0.041, and 0.034 micrograms/mL 1, 2, and 3 hours after dosing 4 mg, respectively. The blood concentrations of the other volunteer were 0.045, 0.056, 0.044 micrograms/mL 1, 2, and 3 hours after dosing 4 mg, respectively.

Any other information on results incl. tables

Emetic action

Dose (mg/kg)

Nos. vomiting

% vomiting response

Total dose (mg)

0.015

0/2

0

1

0.03

4/37

11

2

0.06

1/2

50

4

0.11

1/1

100

8

Applicant's summary and conclusion

Conclusions:
It can be concluded that the test substance can initiate emesis in humans at a dose of approximately 0.03 - 0.11 mg/kg bw (2 - 8 mg).
Executive summary:

Twelve healthy volunteers were orally dosed with 0.25, 0.5, 1.0, 2, 3, 4, and 8 mg. Plasma concentrations of the two volunteers dosed with 4 mg were determined. The blood concentrations of one volunteer were 0.081, 0.041, and 0.034 µg/mL and concentrations of the other volunteer were 0.045, 0.056, 0.044 µg/mL 1, 2, and 3 hours after dosing, respectively. Based on the obtained results further studies were performed with a maximum dose of 2 mg. Of those who took 2 mg test substance (about 0.03 mg/kg) approximately 10% vomited and 60% complained of nausea. It can be concluded that the test substance can initiate emesis in humans at a dose of approximately 0.03 - 0.11 mg/kg bw (2 - 8 mg).