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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature

Data source

Reference
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
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Duration of treatment / exposure:
104 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
500 ppm
Dose / conc.:
5 000 ppm
Dose / conc.:
50 000 ppm
No. of animals per sex per dose:
4
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
Clinical observations were made daily. Body weights and feed consumption were determined weekly for the first 26 wks, biweekly for the second 26 wks, and monthly thereafter.
Sacrifice and pathology:
Clinical pathology studies were performed prior to study initiation and at 4, 13, 26, 52, 78, and 104 wks. One male and one female from each group was killed after 52 wks, and the remaining
animals were killed at study termination.

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Body weight gains were normal for all animals.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
Significant changes were not observed in hematological parameters.
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Significant changes were not observed in blood parameters.
Urinalysis findings:
no effects observed
Description (incidence and severity):
Significant changes were not observed in urine parameters.
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Dose-related differences In absolute and relative organ weights were not found.
Gross pathological findings:
no effects observed
Description (incidence and severity):
Significant lesions were not found at gross examination.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Significant lesions were not found at microscopic examination.
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 000 ppm
Sex:
male/female
Basis for effect level:
other: no effects at highest dose tested

Applicant's summary and conclusion