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EC number: 203-597-8 | CAS number: 108-59-8
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Reference Type:
- secondary source
- Title:
- SIDS Initial Assessment Report For SIAM 20 (Malonic Acid Diesters: Dimethylmalonate, 108-59-8; Diethylmalonate, 105-53-3), April 19-22, 2005 Paris.
- Author:
- OECD SIDS
- Year:
- 2 005
- Bibliographic source:
- UNEP Publications
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Dimethyl malonate
- EC Number:
- 203-597-8
- EC Name:
- Dimethyl malonate
- Cas Number:
- 108-59-8
- Molecular formula:
- C5H8O4
- IUPAC Name:
- dimethyl malonate
- Details on test material:
- Purity: 99.8%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Animals: HSDCpb-WU rats
- Age at study initiation: 11-12 weeks
- Weight at study initiation:
males: 377-379 g, females: 210-219 g
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Males:
Test groups: 39 days, male recovery group: 39 exposure days, 45 test days.
Females:
Treatment groups: 51 +/- 7 days, recovery group: 39 exposure days, 45 test days. - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: Cohabitation period until evidence of pregnancy (sperm in vaginal smear) was observed.
- Proof of pregnancy: sperm in vaginal smear - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Premating exposure period: 2 weeks
exposure period: 39-51 days (from 14 days before mating to day 3 of lactation)
Males:
Test groups: 39 days, male recovery group: 39 exposure days
Females:
Treatment groups: 51 +/- 7 days, recovery group: 39 exposure days - Frequency of treatment:
- once daily, 7 days a week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100, 300, 1000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- Main group: 10 males, 10 females
Recovery groups: 5 males, 5 females - Control animals:
- yes, concurrent vehicle
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
Twice daily: morbidity and mortality. Daily observations for appearance, behaviour, clinical signs and preterminal deaths. Females were observed for signs of difficult and pronlonged parturition.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once before exposure and at least once per week thereafter. Signs included were changes in skin, fur, eyes, mucous membranes, occurrence of secretions or excretions and autonomic activity, changes in gait, posture, response to handling, behavioural changes, difficult or
prolonged parturition.
BODY WEIGHT: Yes
- Time schedule for examinations:
Body weights were recorded at the beginning of the study, at least weekly thereafter and at termination. All dams were weighed on gestation days 0, 7, 14 and 20 and lactation days 0 and 4.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the pre-mating period and the recovery period
- Anaesthetic used for blood collection:No data
- Animals fasted: No data
- How many animals: 5 randomly selected males and females or each group.
- Standard haematological parameters checked
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the pre-mating period and the recovery period
- Anaesthetic used for blood collection:No data
- Animals fasted: No data
- How many animals: 5 randomly selected males and females or each group.
- Standard clinical chemistry parameters checked
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: at the end of the dosing period for males and during the lactation period tor females
- Dose groups that were examined: each group
- Battery of functions tested:
handling observations, open field tests, sensory observations, neuromuscular observations and physiological observations (body temperature - Litter observations:
- All pups from each litter were examined for any external deformities, litter size and sex distribution was determined. Pup weights were recorded on day 0 and 4. All pups were examined for malformations and subject to gross pathological examination. Pup survival index up to lactation day 4 was determined.
- Postmortem examinations (parental animals):
- Organ weights of liver, adrenals, kidneys, thymus, spleen, brain and heart were determined of 5 males and females of each group. Testes and epididymis weights of all adult males of each group were also determined.
Pathology: All adult animals and pups were examined for any structural abnormalities and pathological changes.
Histopathology: The following tissues of 5 males and females of the control and high dose group as well as all animals of the recovery and recovery control groups were examined microscopically: all gross lesions, brain, spinal cord, gastrointestinal tract, liver, kidney, adrenals, spleen, heart, thymus, thyroid, trachea, lungs, testes (fixed in Bouins fluid), epididymes (fixed in Bouins fluid), ovaries, uterus, seminal vesioles, coagulating glands, prostate, urinary bladder, axillary lymph nodes, mesenteric lymph nodes, sciatic nerve, femur with marrow, bone marrow smear. Stages of spermatogenesis and interstitial testicular structure in male gonads were determined additionally. Livers of 5 males and females in the mid and low dose groups and testes of 5 males of the mid and low dose groups were also examined. - Postmortem examinations (offspring):
- Pathology: All adult animals and pups were examined for any structural abnormalities and pathological changes.
- Reproductive indices:
- Fertility index
Gestation index
Number of implantations
Number of corpora lutea
Percentage pre- and post implantation loss - Offspring viability indices:
- Number of pubs born
Number of live litters
Mean litter size index
Mean viable litter size
No. of pubs alive on day 0
Live birth index
Sex ratio at birth (no of males/total number born x 100)
No of pups dead or cannibalised up to day 4
Results and discussion
Results: P0 (first parental generation)
Details on results (P0)
No test item related clinical signs were observed throughout the test and recovery period in any of the dose groups.
BODY WEIGHT AND WEIGHT GAIN
No treatment related effects on body weight and body weight gain were observed.
FOOD CONSUMPTION
No treatment related effects were observed.
HAEMATOLOGY
No treatment related effects were observed.
CLINICAL CHEMISTRY
No treatment related effects were observed.
NEUROBEHAVIOUR
No treatment related changes were observed.
ORGAN WEIGHTS
No treatment related effects were observed.
GROSS PATHOLOGY
No treatment related effects were observed.
HISTOPATHOLOGY:
1000 mg/kg bw: Livers of males and females showed a significantly increased incidence of hepatocellular hypertrophy. The change was considered reversible as the incidence was not significantly increased in the high dose recovery animals.
300 and 100 mg/kg bw: No treatment related changes of the liver were observed.
All other histopathological findings were not considered treatment related.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- 300 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Reversible hepatocellular hypertrophy.
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment related effects have been observed.
Results: F1 generation
Details on results (F1)
Fertility indices for males and females were not statistically different from controls in all dose groups. In the low dose group post implantation loss and consequently the percentage of live pubs born was significantly reduced compared to controls (P <= 0.05). These changes were considered incidental and not treatment related as the effects were not observed at the higher dose groups. No statistical significant differences from controls were observed for the number of pregnancies, number littered, number of live litters, mean litter size, mean viable litter size, sex ratio at birth, number of pups dead at first observation or day 2 to 4, number of live pups on day 0, 3 and 4 and the associated survival indices, external abnormalities of life and dead pups at all dose levels.
A significantly higher percentage of male rats in the low dose group on day 4 was considered incidental and not treatment related as a similar change was not found in the higher dose groups.
The mean number and the mean weight of male and female (and both sexes combined) pups during different intervals of the lactation period were not statistically significantly different from controls except from a significantly lower (P <= 0.05) mean number of female pups on lactation day 4 in the low dose group which was considered incidental and not related to treatment. (For details see table 1 "Any other information on results incl. tables.)
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Remarks:
- devlopmental
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment related effects have been observed.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 1: Reproductive results and indices of various dose groups:
|
Dose (mg/kg bw) |
|||
|
0 |
100 |
300 |
1000 |
Fertility index (%) |
100 |
100 |
100 |
100 |
Duration of gestation |
|
|
|
|
Days ± SD |
22±0.3 |
23±0.5 |
23±0.5 |
22±0.4 |
Gestation index (%) |
100 |
100 |
100 |
100 |
Parturition (%) |
100 |
100 |
100 |
100 |
Effects on sperm |
No treatment related effects |
No treatment related effects |
No treatment related effects |
No treatment related effects |
Number of implantations |
|
|
|
|
Number |
12.3 |
11.8 |
12.0 |
11.6 |
% |
88.1 |
84.7 |
88.9 |
88.6 |
Number of corpora lutea |
|
|
|
|
Number |
14.0 |
13.9 |
13.5 |
13.1 |
Percentage preimplantation loss |
11.9 |
15.3 |
11.1 |
11.4 |
Percentage postimplantation loss |
8.1 |
19.1 |
10.4 |
15.1 |
Number of pubs born |
103 |
76 |
86 |
84 |
Number of live litters |
9 |
8 |
8 |
8 |
Mean litter size index |
11.4 |
9.5 |
10.8 |
10.5 |
Mean viable litter size |
11.3 |
9.5 |
10.8 |
9.9 |
Number of pubs alive on day 0 |
102 |
76 |
86 |
79 |
Live birth index |
99 |
100 |
100 |
94 |
Sex ratio at birth (Number of males/total number born x 100) |
46.6 |
60.5 |
54.7 |
46.4 |
24 hour survival (%) |
100 |
100 |
100 |
100 |
|
|
|
|
|
|
|
|
|
|
Number of pubs alive on day 4 of lactation |
101 |
75 |
83 |
78 |
Day 4 survival index |
99.0 |
98.7 |
96.5 |
98.7 |
Sex ratio day 4 |
44.7 |
60.5 |
53.5 |
41.7 |
Number of pups dead or cannibalised up to day 4 |
2 |
1 |
3 |
6 |
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.
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