Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
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

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The Metabolism of L- and DL-Malic Acids by Rats
Author:
Daniel, J.W.
Year:
1969
Bibliographic source:
Fd Cosmet. Toxicol. Vol. 7, pp. 103-106
Reference Type:
review article or handbook
Title:
Final Report on the Safety Assessment of Malic Acid and Sodium Malate
Author:
Fiume MZ, Bergfeld WF, Belsito DV, Klaassen CD, Schroeter AL, Shank RC, Slaga TJ, Snyder PW, and Andersen FA
Year:
2001
Bibliographic source:
Int J Toxicol 20 (Suppl 1): 47-55

Materials and methods

GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Radiolabelling:
yes
Remarks:
U-14C-L-Malic Acid (sp. act. 61 µC/mmol)

Test animals

Species:
rat
Strain:
Wistar
Remarks:
albino Wistar Aldarly Park SPF rats
Sex:
male

Administration / exposure

Route of administration:
other: oral or by intraperitoneal (i.p.) injection
Vehicle:
not specified
Doses / concentrations
Dose / conc.:
2.5 mg/kg bw/day (nominal)
No. of animals per sex per dose:
The number of animals per group was not specified.
Control animals:
not specified
Details on dosing and sampling:
Urine, feces, and expired carbon dioxide were collected.

Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
Most of the radioactivity was excreted as carbon dioxide; after 24 h, 88.0 and 86.6% of orally and intraperitoneally administered L-Malic Acid, respectively, was found in expired air.
Type:
excretion
Results:
The amount of radioactivity recovered after oral and i.p. administration of L-Malic Acid was 3.2 and 3.1% in the urine and 1.4 and 1.4% in the feces, respectively.
Type:
excretion
Results:
After 24 h, the total amount of radioactivity recovered was 92.6 and 91.1% after oral and i.p. administration of L-Malic Acid, respectively.

Any other information on results incl. tables

L-Malic acid was rapidly and extensively metabolized when administered to rats by either the oral or the intraperitoneal route. In each case most of the radioactivity (83-92 %) was excreted within 24 hr as carbon dioxide in the expired air. Only small amounts of radioactivity were found in the urine (3-9 %) and

faeces (0.3-1.4 %).

Applicant's summary and conclusion