4-methylcyclohexanone

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Remarks:

review article

Adequacy of study:

other information

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

review article or handbook

Title:

Pharmacodynamie. --Toxicité de la cyclohexanone et de quelques cétones homologues

Author:

Caujolle F; Couturier P; Roux G; Gasc Y, présentée par Bertrand MG

Year:

1953

Bibliographic source:

Comptes Rendus Hebdomadaires des Séances, Academie des Sciences, Vol 236 (6); Pg. 633 to 635, 1953

Materials and methods

GLP compliance:

no

Results and discussion

Any other information on results incl. tables

For each of the three Methylcyclohexanones' isomers 7 animals were used.

Lethal doses were:

4 -Methylcyclohexanone: 0.37 g/kg

3 -Methylcyclohexanone: 0.31 g/kg

2 -Methylcyclohexanone: 0.27 g/kg

Blood pressure decreases either instantly or within 5 to 6 min., then the hypotension stays in the level or aggravates progressively until death. The heart slows down and sometimes even a clear bradycardia occurs (pulse 70). Generally starting from the beginning of the intoxination an intensive polypnea can be observed, with reduction of the respiratory amplitude.

The polypnea takes until the last minutes of the test. The terminal apnoea establishes very suddenly, often without any premonitory sign.

The intensity of the oculo cardiac reflex decreases during the first phases of intoxination; in some rare cases even an inversion of this reflex can be observed.

Similarly the responses on the pinching of the carotids diminish fast and cease as soon as half of the lethal dose was adminstered.

During the intoxination the azotemia and the cholesterolemia only slightly changed, but glycemia tends to increase notably.

The methylation of cyclohexanone inceases its toxicity.

Toxicity increases in the following sequence: 4 -methylcyclohexanone to 3 -methylcyclohexanone to 2 -methylcyclohexanone.

Applicant's summary and conclusion

Conclusions:

Te lethal dose of 4-methylcyclohexanone administered intravenously to dogs was determined to be 0.37 g/kg.

Executive summary:

The acute toxicity of 4 -methylcyclohexanone was determined using 50% solutions of test substance in neutralized olive oil which were prepared and injected by continued infusion into the central end of saphenous of dogs treated with Chloralose (0,10 g/kg) as an anesthetic and sedative.

Criteria for the death: stop of heartbeat, determined by recording the central pressure.

Seven animals were used.

Lethal dose was:

4 -Methylcyclohexanone: 0.37 g/kg

Blood pressure decreases rapidly, then the hypotension until death. The heart slows down and sometimes even a clear bradycardia occurs (pulse 70). Starting from the beginning of the intoxination an intensive polypnea can be observed, with reduction of the respiratory amplitude.

The intensity of the oculo cardiac reflex decreases during the first phases of intoxination; in some rare cases even an inversion of this reflex can be observed.

During the intoxination the azotemia and the cholesterolemia only slightly changed, but glycemia tends to increase notably.