Piperidine

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

BIOCHEMICAL STUDIES OF SIX NITROGEN-CONTAINING HETEROCYCLES IN RAT TISSUES

Author:

Kitchin, K.T. et al.:

Year:

1989

Bibliographic source:

Biochem. Pharmacol. 38, 2733-2738

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats were treated orally with the test compound at 21 and 4 hours before they were killed. Biochemical examinations were performed in different tissues and blood.

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

basic toxicokinetics

Test material

Test material information

Constituent 1

Reference substance name:

Piperidine

EC Number:

203-813-0

EC Name:

Piperidine

Cas Number:

110-89-4

Molecular formula:

C5H11N

IUPAC Name:

piperidine

Specific details on test material used for the study:

- Name of test material (as cited in study report): piperidine
- Analytical purity: 98 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories (Wilmington, MA)
- Age at study initiation: 90 days
- Housing: 3 per cage

ENVIRONMENTAL CONDITIONS
- no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

physiological saline

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
- Piperidine was diluted with 0.9 % saline solution. Solution was adjusted to pH 7.0 before use.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Single treatment 21 and 4 hours before killing.

Frequency of treatment:

once

Post exposure period:

21 and 4 hours

Doses / concentrations

Dose / conc.:

80 mg/kg bw/day (actual dose received)

Remarks:

corresponding to 1/5 of the published LD50

No. of animals per sex per dose:

Piperidine: 7 animals; control: 8 animals

Control animals:

yes, concurrent vehicle

Details on study design:

- Leukocytes were separated from erythrocytes;
- Subcellular fractions were prepared from liver and esophagus:
• liver tissue was homogenized and used for alkaline elution.
• esophagus tissue digestion and lysis (on the filter) was performed to reduce DNA damage observed with homogenization.
- alkaline elution procedure was performed according to Kohn KW et al., 1981 (DNA Repair, A Laboratory Manual of Research Procedures (Eds. Hanawalt PC and Friedberg EC), pp 379-401. Marcel Dekker, New York).
- Assays for ODC activity, glutathione content, cytochrome P-450 content and SGPT activity were performed by standard methods.
- Statistical analysis of the data was done with analysis of variance. Statistically significant differences found by a Tukey's test were then further evaluated with a Student's t-test.

Examinations

Examinations:

- hepatic DNA damage
- ornithine decarboxylase (ODC) activity
- serum alanine aminotransferase (SGPT) activity
- cytochrome P-450
- glutathione content

Results and discussion

Details on results:

- Prior to sacrifice no animals died and no obvious clinical signs of toxicity were visually noted.
- Piperidine (80 mg/ kg bw) did not alter any of the six biochemical parameters:
• Blood alkaline elution (fraction of DNA eluted): Control: 0.070 ± 0.021; Piperidine 0.049 ± 0.011
• Liver alkaline elution (fraction of DNA eluted): Control: 0.100 ± 0.010; Piperidine 0.101 ± 0.009
• Liver ornithine decarboxylase (nmol CO2/g liver / hr): Control: 1.44 ± 0.32; Piperidine 3.13 ± 0.82
• Liver glutathione (µmol/g): Control: 3.94 ± 0.39; Piperidine 3.34 ± 0.33
• Liver cytochrome P-450 (nmol/g): Control: 3.52 ± 0.36; Piperidine 4.13 ± 0.33
• Serum alanine aminotransferase (I.U./I.): Control: 11.1 ± 0.8; Piperidine 12.3 ± 2.1 (this parameter was determined in 6 animals treated with piperidine).