Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-601-5 | CAS number: 97-67-6
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
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:
- 2 001
- Bibliographic source:
- Int J Toxicol 20 (Suppl 1): 47-55
Materials and methods
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- L-malic acid
- EC Number:
- 202-601-5
- EC Name:
- L-malic acid
- Cas Number:
- 97-67-6
- Molecular formula:
- C4H6O5
- IUPAC Name:
- malic acid
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- days 6 through 15 of gestation
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 3.5 mg/kg bw/day
- Dose / conc.:
- 16.2 mg/kg bw/day
- Dose / conc.:
- 75.4 mg/kg bw/day
- Dose / conc.:
- 350 mg/kg bw/day
- No. of animals per sex per dose:
- 25-29
- Control animals:
- yes
Examinations
- Ovaries and uterine content:
- The number of implantation sites, resorption sites, and live and dead neonates was determined on day 20 of gestation.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- All animals except three of the 350 mg/kg test group (two were gravid) survived until study termination.
- Body weight and weight changes:
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- The researchers concluded that "the administration of up to 350 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- At gross examination, 20/25, 21/29, 22/25, and 26/28 animals of the 3.5, 16.2, 75.4, and 350 mg/kg dose groups, respectively, were gravid.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day
- Basis for effect level:
- other: highest dose level tested was without effects
Results (fetuses)
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- The researchers concluded that "the administration of up to 350 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- not specified
- Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The number of abnormalities seen in skeletal tissues of the test groups did not differ from the number occurring spontaneously in sham-treated controls."
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The number of abnormalities seen in soft tissues of the test groups did not differ from the number occurring spontaneously in sham-treated controls."
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 350 mg/kg bw/day
- Basis for effect level:
- other: highest dose level tested was without effects
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
