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EC number: 203-743-0 | CAS number: 110-17-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- other: Safety assessment
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Peer-reviewed safety assessment by the Cosmetic Ingredient Review Expert Panel.
Data source
Reference
- Reference Type:
- publication
- Title:
- Final report on the safety assessment of malic acid and sodium malate
- Author:
- Fiume MZ
- Year:
- 2 001
- Bibliographic source:
- Int J Toxicol 20 Suppl 1: 47-55
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- Peer-reviewed safety assessment by the Cosmetic Ingredient Review Expert Panel.
- GLP compliance:
- not specified
- Remarks:
- published review
- Limit test:
- no
Test material
- Reference substance name:
- Malic acid
- EC Number:
- 230-022-8
- EC Name:
- Malic acid
- Cas Number:
- 6915-15-7
- IUPAC Name:
- malic acid
- Details on test material:
- Malic acid is a metabolite of fumaric acid.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- not specified
- Details on test animals or test system and environmental conditions:
- No further animal information available.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Rats were fed 1000 or 10000 ppm malic acid for 9 weeks prior to mating for the F1A litter and through weaning of the F1B litter.
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Rats were fed 1000 or 10000 ppm malic acid for 9 weeks prior to mating. One week after weaning of the last F1A litter, the P1 parents were remated to produce the F1B litter. Ten male and 20 female weanlings from each dose group were selected for the P2 generation and administered the appropriate diets. The animals were mated at 100 days of age to produce the F2A generation. One week after weaning of the F2A litter, the P2 parents were remated to produce the F2B litter.
- Duration of treatment / exposure:
- 9 weeks
- Frequency of treatment:
- Daily in feed
- Duration of test:
- Multi-generation study
Doses / concentrations
- Remarks:
- Doses / Concentrations:
1000 or 10000 ppm
Basis:
nominal in diet
- No. of animals per sex per dose:
- 10 males and 20 females per dose
- Control animals:
- yes, plain diet
- Details on study design:
- No further information available
Examinations
- Maternal examinations:
- Body weight gain, feed consumption, survival, appearance and behavior were evaluated.
- Ovaries and uterine content:
- Various indices and litter sizes were evaluated.
- Fetal examinations:
- Pup body weights were determined.
- Statistics:
- No information available.
- Indices:
- No information available.
- Historical control data:
- No information available.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Body weight gain of female animals were comparable to controls prior to mating. Body weight gains of male animals in test groups were slightly decreased compared to controls. Feed consumption, survival, appearance and behavior were similar for P1 test and control rats. The P2 test and control animals were similar throughout the study and wheezing was observed in all groups during the F2B phase.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 000 ppm (nominal)
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
F1A: all necropsied pups from low dose group had rough surfaces on the spleen
F2A: the number of pups that were weak or had labored respiration during lactation was increased in the high dose group. No abnormal findings were reported at necropsy.
F2A: Renal discoloration, dark renal medullas and rough surfaces on the spleen where seen at both dose levels at necropsy. In addition, low dose animals had white foci on spleen. High dose animals also had dark red corticomedullary zones and a firm, enlarged, irregularly-shaped cecum with a hole penetrating it.
F2B litters delivered naturally showed weakness and labored respiration in the low dose group and the renal pelvis of one high-dose pup was dilated at necropsy.
F2B litters delivered by caesarean section showed no differences when compared to controls.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- > 10 000 ppm (nominal)
- Remarks on result:
- other: not determinable/no NOAEL identified
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
The F2B generation showed no meaningful differences between test and control animals in the number and placement of implantation and resorption sites or in the number, weight, or length of live neonates, and none of the neonates died. The skeletal development of F2B neonates was similar between test and control animals. Slight differences in developmental indices were considered to be within the range of normal variations in fetal development and no trend toward lesser or greater skeletal development was observed.
Applicant's summary and conclusion
- Conclusions:
- This safety assessment supports the conclusion that malic acid, a metabolite of fumaric acid, is not a developmental toxicant.
- Executive summary:
Malic acid was administered to rats at doses of 1000 or 10,000 ppm in the diet for 9 weeks prior to mating through weaning. Weanlings from this group were selected for the P2 generation and fed a similar diet. For all litters, various indices, litter sizes and pup body weights were comparable to controls and no significant differences in skeletal development were observed. Similar results would be expected with the closely related chemical, fumaric acid, and no toxic effects on the development of offspring are likely to be seen.
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