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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: MIGRATRED DATASET. Relevant (or significant) methodological deficiencies: limited documentation

Data source

Reference
Reference Type:
publication
Title:
Antihyperlipidemic activity of phthalimide analogues in rodents.
Author:
Hall IH, Voorstad PJ, Chapman JM, and Cocolas GH
Year:
1983
Bibliographic source:
J. Pharm. Sci. 72, 845-851.

Materials and methods

Principles of method if other than guideline:
migrated dataset
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: other TS: purity not indicated

Test animals

Species:
mouse
Strain:
other: CF1
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
9 - 16 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
5 - 60 mg/kg bw/day
Control animals:
yes
Details on study design:
Post-exposure period: no

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Migrated dataset

RS-Freetext: Mice maintained on standard food: Reduced serum cholesterol and triglyceride levels were observed in all dose groups (0, 5, 10, 20, 50 mg/kg bw/day). Serum cholesterol level were 100, 67, 62, 49, and 51%, respectively, at day 9, and 100, 43, 59, 45, and 40%, respectively, at day 16. Triglyceride level was 100, 46, 44, 52, 56%, respectively, at day 14. In liver homogenates of mice dosed with 0, 10 , 20, 40, and 60 mg/kg bw/day the following enzymatic activities were observed (enzyme activity of control mice was set to 100%): AcCoA synthetase: 100, 76, 76, 75, 84% HMG CoA reductase: 100, 89, 89, 88, 105% Acetyl CoA carboxylase: 100, 60, 62, 56, 57% phosphatidate phosphohydrolase: 100, 91, 67, 29, 3% and fatty acid synthetase.100, 79, 78, 82, 76% the lipid contents of the liver, and the small intestine were as following: liver lipids: 100, 70, 70, 68, 64% small intestine lipids: 100, 106, 58, 77, 88% The cholesterol level, triglycide level, and phospholipid content in the liver and the small intestine was as following: Liver: Total cholesterol: 100, 74, 34, 56, 63% Neutral lipids: 100, 51, 36, 18, 15% Triglycerides: 100, 37, 31, 38, 30% Phospholipides: 100, 74, 144, 139, 137% Small intestine: Total cholesterol: 100, 108, 242, 204% Neutral lipids: 100, 78, 48, 55, 70% Triglycerides: 100, 109, 62, 70, 93% Phospholipides: 100, 101, 48, 44, 74% Hyperlipidemic-induced mice: Reduced serum cholesterol level were observed in hyperlipidemic-induced mice dosed with phthalimide compared to hyperlipidemic-induced mice not doesed with phthalimid. Serum cholesterol levels were 100, 289 and 137% for control mice maintained on standard diet, hyperlipidemic-induced mice, and hyperlipidemic-induced mice dosed with 20 mg/kg bw/day of phthalimide, respectively. Triglyceride level were reduced below normal level in hyperlipidemic-induced mice dosed with phthalimide. Serum triglyceride levels were 100, 131 and 57% for control mice maintained on standard diet, hyperlipidemic-induced mice, and hyperlipidemic-induced mice dosed with 20 mg/kg bw/day of phthalimide, respectively. Conclusion: phthalimide lowered serum cholesterol and triglyceride level after i.p. application in mice maintained on a standard diet and in hyperlipidemic-induced mice.

Applicant's summary and conclusion