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Repeated dose toxicity: oral

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Administrative data

short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study, a reliability of 2 is assigned

Data source

Reference Type:
Hypolipidemic activity of aliphatic dicarboxylic acids in rodents.
Izydore RA, Hall IH
Bibliographic source:
Acta Pharm. Nord. 3 (3): 141-146

Materials and methods

Principles of method if other than guideline:
The hypolipidemic activity of maleic acid was investigated.
GLP compliance:
not specified

Test material

Details on test material:
Maleic acid, no data on purity

Test animals

Details on test animals and environmental conditions:
- Mean body weight 350 g
- Food and water were available ad libitium for animals in experiments. The animals were maintained in plastic cages in 12 h cycles of light and dark at 22°C.

Administration / exposure

Route of administration:
oral: gavage
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Frequency of treatment:
Doses / concentrations
Doses / Concentrations:
20 mg/kg/d
actual ingested
No. of animals per sex per dose:
6 males
Control animals:
Details on study design:
Post-exposure period: none


Observations and examinations performed and frequency:
Food consumption was determined daily for control rats and for those treated orally with compounds. Body weights were obtained during the experiments and expressed a percentage of the animals weight on day 0. After dosing for 14 days with compounds, selected organs were excised, trimmed of fat and weighed. On days 7 and 14, blood samples were taken and examined for serum lipids. After termination of administration, the liver, small intestine, aorta, and fecal materials (24 h collection) were removed, extracted and analyzed for tissue lipid levels (cholesterol, triglyceride, neutral lipids, and phospholipids) and protein levels; serum was examined for lipoprotein contents.

Results and discussion

Results of examinations

Details on results:
Body weight and food consumption
Food consumption of the treated rats was suppressed by 6% compared to controls, however, total body weight and organ weights were not altered significantly by drug treatment.

Clinical chemistry
Serum levels of free and total cholesterol were significantly decreased on days 7 and 14 (about half the control values); serum levels of triglycerides were also significantly decreased on days 7 and 14 (about three quarters of control values). Lipid content was significantly decreased in liver extract and significantly increased in fecal extract. In liver tissue, the levels of free and total cholesterol, triglyceride, and phospholipids were significantly decreased. In the small intestinal mucosa, levels of free and total cholesterol and phospholipids were significantly decreased. In aorta wall tissue, the level of free and total cholesterol was significantly decreased. In feces, levels of free and total cholesterol and triglyceride were significantly increased. The levels of neutral lipids were not significantly altered in any examined tissues. Protein content was significantly increased in tissue of the aorta wall and in feces. After 14 days of treatment, the serum levels of free and total cholesterol of the VLDL and LDL fraction were significantly decreased. HDL triglyceride content was significantly increased while the triglyderide content of the chylomicron fraction was significantly decreased. Neutral lipid content of serum was significantly decreased in chylomicron, VLDL, LDL, and HDL. Phospholipid levels were significantly increased in chylomicron and LDL fraction and significantly decreased in VLDL fraction. Chylomicron and VLDL protein content was significantly increased; LDL protein content was significantly decreased.

Effect levels

Dose descriptor:
Effect level:
20 mg/kg bw/day (nominal)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

According to the authors, the findings showed that maleic acid was an effective 
hypolipidemic agent in rats.

Applicant's summary and conclusion