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EC number: 203-571-6 | CAS number: 108-31-6
- 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:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented publication and study report which meets basic scientific principles.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 986
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Maleic anhydride
- EC Number:
- 203-571-6
- EC Name:
- Maleic anhydride
- Cas Number:
- 108-31-6
- Molecular formula:
- C4H2O3
- IUPAC Name:
- furan-2,5-dione
- Details on test material:
- Maleic anhydride was supplied by Monsanto Company as white briquettes with a purity of greater than 99%.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Adult CD rats (Charles River Breeding Laboratories, Wilmington, Mass.), approximately 12 weeks of age, were used in the teratology study.
All rats were acclimated to the laboratory for at least 10 days prior to initiating a study. Rats were individually housed, except during mating and lactation, in wire mesh cages or plastic cages with corn-cob bedding. All animals were maintained in environmentally controlled rooms with 12-hr photoperiods and given free access to feed (Purina Rodent Chow, Ralston-Purina, St. Louis, Mo.) and water.
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- corn oil
- Details on exposure:
- Briquettes of maleic anhydride were finely ground with a mortar and pestle and suspended in corn oil with the aid of a tissue homogenizer. All doses were prepared daily in corn oil in order to minimize problems with stability. A 1% (w:v) concentration was used to administer all doses.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- One male and one female were housed together for mating.
- Duration of treatment / exposure:
- Day 20 of gestation
- Frequency of treatment:
- Day 6-15 of gestation
- Duration of test:
- not specified
Doses / concentrations
- Remarks:
- Doses / Concentrations:
30, 90, and 140 mg/kg/day
Basis:
- No. of animals per sex per dose:
- 25 mated females/group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: In a pilot study, conducted to identify doses for the teratology study, three of five and five of five dams died after doses of 192 and 256 mg/kg, respectively, of maleic anhydride.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 20
- Organs examined: no data - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
- Fetal examinations:
- All fetuses were weighed and examined for external abnormalities. Approximately one-third of the fetuses were placed in Bouin's fixative and examined for soft tissue abnormalities (Wilson, 1965). The remaining fetuses were fixed in alcohol, cleared with potassium hydroxide, stained with Alizarin Red S (Dawson, 1926), and examined for skeletal abnormalities.
- Statistics:
- Statistical analysis. Several different statistical methods were used to compare measurements made on test animals to the corresponding values determined for controls. The methods and the measurements to which they were applied are analyis of variance and Dunnett's test (Steel and Torrie, 1960) for adult body weights, litter size, and pup body weights; Fisher's exact probability test (Siegel, 1956) for mortality and fertility data; Mann-Whit-ney U test (Siegel, 1956) for fetal body weights; and x2 test with Yates' correction or Fisher's exact probability test (Siegel, 1956) for litters with anomalies. In all instances, p < 0.05 was selected as the level of significance.
- Indices:
- no data
- Historical control data:
- yes
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
The general appearance and behavior of rats were not altered by treatment. While one adult died in each of the experimental groups, the overall survival in these groups was 96% (Table 1). Dams in the experimental groups either failed to gain weight or lost weight between Days 6 and 9 of gestation (Table 1). However, this effect was reversible, and there were no statistically significant effects on body weight at any of the times examined.
Dams from all test groups produced normal-sized litters, and there was no evidence of postimplantation loss.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Compared with concurrent controls, fetal body weights were slightly reduced for all test groups, but the reductions were statistically significant only in the low- and high-dose groups. However, this is not considered to be compound-related, because fetal weights for concurrent control and all treated groups were slightly greater than the values for historical controls.
The malformations and variations observed during the fetal examinations are summarized in Table 2. Malformations were observed in one fetus (one litter) from the control group, two fetuses (two litters) from the low-dose group, and three fetuses (three litters) from the high-dose group. Since each malformation was a single occurrence and the malformations differed among the various groups, there was no evidence of a dose-related increase in any specific malformation. The fetal variations were comparable both in type and frequency in the control and treated groups.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOAEL
- Effect level:
- 140 mg/kg bw/day
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Maleic anhydride (mg/kg/day) |
||||
|
0 |
30 |
90 |
140 |
Number treated |
25 |
25 |
25 |
25 |
Pregnant |
23 |
24 |
20 |
21 |
Alive |
23 |
23 |
19 |
21 |
Nonpregnant |
2 |
1 |
5 |
4 |
Alive |
2 |
1 |
5 |
3 |
Body weight (g) |
|
|
|
|
Day 0 |
242 |
244 |
242 |
243 |
Day 6 |
261 |
264 |
266 |
264 |
Day 9 |
272 |
264 |
264 |
258 |
Day 12 |
293 |
286 |
283 |
282 |
Day 15 |
315 |
302 |
303 |
298 |
Day 20 |
397 |
377 |
385 |
378 |
Implants/dam |
13.3(14)a |
13.4(14) |
13.2(13) |
13.5(14) |
Viable fetuses/dam |
12.6(13) |
12.7(13) |
12.5(13) |
12.7(13) |
Resorptions/dam |
0.8 (0) |
0.7(0) |
0.7(1) |
0.8 (0) |
Fetal weight (g) |
4.0(3.8) |
3.7(3.8)b |
3.8(3.8) |
3.7 (3.6)b |
" Mean (median).
* Mean significantly different from control. The historical control value for fetal weight was 3.6 g for 1774 fetuses.
OBSERVATIONS OF FETUSES FROM RATS TREATED WITH MALEIC ANHYDRIDE DURING GESTATION
Maleic anhydride (mg/kg/day) |
||||
|
0 |
30 |
90 |
140 |
Number examined |
|
|
|
|
Litters |
23 |
23 |
19 |
21 |
Fetuses |
|
|
|
|
External |
289 |
292 |
237 |
267 |
Skeletal |
189 |
190 |
155 |
174 |
Soft tissue |
100 |
102 |
82 |
93 |
Malformations |
|
|
|
|
Short tail |
— |
1(1)a |
— |
— |
Omphalocele |
— |
— |
— |
1(1) |
Spherical enlargement on ribs |
1(1) |
— |
— |
— |
Fused sternebrae |
— |
1(1) |
— |
— |
Bent ribs |
— |
— |
— |
1(1) |
Multiple anomalies |
— |
— |
— |
1(1)b |
Total with above malformations |
1(1) |
2(2) |
0(0) |
3(3) |
Variations |
|
|
|
|
Rudimentary 14th rib(s) |
51(17) |
62 (20) |
46(16) |
37(13) |
Full 14thrib(s) |
1(1) |
2(2) |
3(3) |
1(1) |
27 presacral vertebrae |
— |
5(4) |
2(1) |
2(2) |
Sternebrae 5 and/or 6 unossified |
12(9) |
16(7) |
12(6) |
20(12) |
7th cervical rib |
3(2) |
1(1) |
1(1) |
— |
Misaligned centra |
— |
— |
— |
1(1) |
Reduced ossification of skull |
— |
1(1) |
— |
1(1) |
Hyoid unossified |
— |
5(3) |
— |
— |
Pubis unossified |
— |
1(1) |
— |
— |
Renal papillar not developed |
2(2) |
— |
— |
1(1) |
" Number of fetuses (number of litters).
* Includes malformed humerus, stemoschisis, and ossification defects of the pubis, cervical arches, and skull.
Applicant's summary and conclusion
- Conclusions:
- There was, however, no maternal NOEL because females at 30 mg/kg failed to gain weight from gestation day 6-9 although this was not statistically significant. The NOAEL for both maternal and developmental toxicity was 140 mg/kg/day.
- Executive summary:
The maternal toxicity effects are likely to reflect the toxicity of maleic acid since maleic anhydride is rapidly hydrolyzed to maleic acid in the body, particularly by the oral route of exposure.
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