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EC number: 201-297-1 | CAS number: 80-62-6
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- before 27th June 2018
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.4350 (Inhalation Developmental Toxicity Screen)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- - Supplier: Rohm and Haas Company
- Purity= 99.9 % - Species:
- rat
- Strain:
- other: Crl:CDBR
- Details on test animals or test system and environmental conditions:
- - 225 nulliparous female rats
- Source: Charles River Breeding Laboratories Inc., Kingston, NY
- Age at study initiation: 81 -88 days
- AGE AT TIME OF MATING: 88-95 days.
- Weight at study initiation: 183-240 grams upon arrival
- Fasting period before study:
- Housing: Animals were housed individually, except during mating, in suspended stainless-steel cages (7" x 8" x 13.5"). During exposures, females were housed individually in suspended stainless-steel, wire mesh cages (6" x 7" x 11").
- Diet (e.g. ad libitum): Food (Certified Purina Rodent Chow #5002 ad libitum except during exposures.
- Water (e.g. ad libitum): filtered tap water ad libitum except during exposures.
Neither feed nor water was available during the 6 hour exposure period.
- Acclimation period: 7 days prior to mating
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): ranged from 40-60% during cohabitation and 63-80% during the exposure and postexposure
periods.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light was maintained - Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The test material exposure concentrations were generated by metering the test material with calibrated Fluid Metering Pumps (Fluid Matering Inc., Oyster Bay, NY) into 500 mL three-necked round bottom flasks (Lab Glass Inc., Vineland, NJ).
Exposures were whole body and were conducted in 2000 L stainless steel, glass and Plexiglas® chambers. Cage positions within the chamber were rotated daily. The temperature and relative humidity within the chambers during exposure were 22-24°C and 55-67%, respective. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration of the test substance in the chambers was determined by the use of a Miran gas analyzer attached to a strip chart recorder. A probe was placed into the center of the chamber and the chamber atmosphere was drawn into the Miran A1 gas analyzer at a rate of 9.5 L/min. Each chamber was analyzed initially within 40 min. of the end of the t99 to insure that each chamber was within the accepted target range. Subsequently, each chamber was sampled every 120 min. A range of plus or minus 10% of the target chamber concentration was maintained by making minor adjustments on the generator pump delivery rates whenever necessary.
Target concentrations [ppm] Analytical concentrations [ppm]
mean +/- SD
--------------------------------------------------------------------------------
100 98.8 ± 3.4
300 304.4 ± 9.1
1200 1178.1 ± 69.1
2000 2028.2 ±107.3 - Details on mating procedure:
- Females were mated with males overnight (one male:one female) and the presence of sperm in the vaginal smear was considered gestation day 0. Mated females were exposed via inhalation to the test material for 6 hrs/day on gestation days 6 through 15 and then sacrificed on day 20.
- Duration of treatment / exposure:
- 6 - 15 day of gestation
- Frequency of treatment:
- 6 hours/day
- Duration of test:
- 20 d (dams were euthanized on gestation day 20)
- Dose / conc.:
- 99 ppm
- Remarks:
- corresponding to 412 mg/m3 or 0.41 mg/L
- Dose / conc.:
- 304 ppm
- Remarks:
- corresponding to1285 mg/m3 or 1.29 mg/L
- Dose / conc.:
- 1 178 ppm
- Remarks:
- corresponding to 4900 mg/m3 or 4.9 mg/L
- Dose / conc.:
- 2 028 ppm
- Remarks:
- corresponding to 8436 mg/m3 or 8.44 mg/L
- No. of animals per sex per dose:
- 27 animals per group exposed; 22-25 pregnant females per exposure group.
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Other: The strain was selected because background development toxicity data exists as Rohm and Haas Company on this rat strain. The test material was given by inhalation since the respiratory route is a potential route of human exposure.
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals were observed daily for behavioral changes.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily GD 0 - 20
BODY WEIGHT: Yes
- Time schedule for examinations: recorded on GD 0, 6, 8, 10, 13, 16 and 20.
Food consumption was measured for GD intervals 0-6, 6-10, 10-16 and 16-20.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
A limited necropsy was performed on all adult female animals. During the necropsy, animals were ex
amined for evidence of pregnancy
and gross lesions of the abdominal and thoracic cavities. Each uterus was weighted. - Ovaries and uterine content:
- On GD 20, all dams were asphyxiated with carbon dioxide, the thoracic and abdominal cavities were examined and the uterus was removed and weighed, and corpora lutea, implantation sites and resorptions were counted. The number of fetuses per litter was counted and position inside the uterus recorded. The uteri of apparently non pregnant rats were stained with a 10% ammonium sulfide solution to detect very early resorptions. All fetuses were weighed, examined for external alterations and the sex of each fetus was determined.
- Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: Yes: [half per litter ]
One half of the fetuses from each litter were examined for visceral alterations using the Staples' technique. Head alterations were recorded for these fetuses examined for soft tissue alterations using the technique of Barrow and Taylor (1969, J. Morphol., 127: 291-306). The carcasses of all fetuses were stained with alizarin red S and examined for skeletal alterations. - Statistics:
- For the purpose of statistical evaluation, the litter was considered the experimental unit for fetal parameters. Pregnancy rate, clinical signs, maternal deaths, gross necropsy findings and liters with total resorptions were statistically analyzed using the Fisher's exact test. Maternal body weight data and feed consumption values were statistically analyzed using Dunnett's test when the one-way ANOVA was significant. The number of implantations, live fetuses, resorptions, corpora lutea, mean fetal body weight/litter, and incidence of fetal alterations were statistically analyzed using the Mann-Whitney U test. When more than 75% ties occurred, then Fisher's exact test was used in place of the Mann-Whitney U test to detect significant differences between groups.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related clinical signs were observed bevore, during, or after the exposures at any exposure levels tested.
The only clinical sign noted was a minimal (only noted once or twice in 6 of 7 affected females) increase in the incidence of scant feces at 2028 ppm. - Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- There were no test substance-related or spontaneous mortalities in any group.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment-related decreases on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they occurred only during the first 2 days of exposure and returned to control values by the next weighing period. In addition, maternal body weight gain over the entire treatment period (days 6-16 G) and corrected maternal body weight gain at 99 and 304 ppm were similar to the control values. The body weight and feed consumption values returned to control values for all groups during the post exposure period (GD 16-20). At 1178 and 2028 ppm, treatment-related effects included losses in maternal body and/or decreased body weight gain throughout the exposure period (GD 6 - 16) and decreased corrected maternal body weight gain (body weight gain minus gravid uterine weight).
Body weight during gestation in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Mean Body weight [g] ± SD
[ppm], 6 h/day on GD 0 on GD 6 on GD 8 on GD 10 on GD 13 on GD 16 on GD 20
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 244.7 ±3.13 285.6 ± 3.93 295.4 ±4.33 307.1 ±4.20 327.3 ±4.68 350.6 ±5.05 414.2 ±6.84
99 23 246.3 ±2.93 286.1 ± 3.56 289.9 ±4.01 304.8 ±3.99 325.4 ±4.31 351.8 ±4.72 416.6 ±6.87
304 22 248.7 ±2.62 286.2 ± 3.11 288.9 ±3.60 301.3 ±3.91 321.1 ±4.09 347.1 ±4.58 413.9 ±6.09
1178 23 244.9 ± 2.77 282.2 ± 3.53 278.1a ±3.96 289.0a ±3.94 308.3a ±4.04 334.6 ±4.88 400.4 ±6.80
2028 23 246.7 ± 2.85 286.4 ± 3.03 275.2a ±2.68 280.9a ±3.40 306.2a ±3.49 332.7a ±4.27 401.3 ±5.56
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Change in weight during gestation in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Mean body weight gain ± SD on GD [g]
[ppm], 6 h/day on GD 0 - 6 on GD 6 - 8 on GD 8 - 10 on GD 10-13 on GD 13-16 on GD 6-16 on GD 16-20
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 41.0 ±1.86 9.8 ±0.83 11.6 ±0.58 20.3 ±0.94 23.2 ±1.76 65.0 ±2.33 63.6 ±2.75
99 23 39.7 ±2.36 3.8a ±1.39 15.0 ±1.90 20.5 ±1.28 26.4 ±1.52 65.7 ±2.83 64.8 ±3.81
304 22 37.5 ±2.05 2.7a ±1.09 12.4 ±1.09 19.8 ±1.04 26.0 ±1.30 60.9 ±2.62 66.8 ±2.54
1178 23 37.3 ±1.91 -4.1a ±-1.41 10.9 ±0.91 19.3 ±1.09 26.3 ±1.76 52.4a ±2.56 65.8 ±3.15
2028 23 39.7 ±1.08 -11.2a ±0.88 5.7a ±2.24 25.4a ±1.62 26.5 ±1.99 46.4a ±2.35 68.6 ±2.12
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Summary of Uterine and Net body weights in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Gravid Uterus weight ± SD [g] Corrected Mean body weight ± SD on GD 20 [g] Net weight change ± SD from GD 6 [g]
[ppm], 6 h/day
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 82.7 ±3.81 331.5 ±4.77 45.8 ±2.21
99 23 82.7±5.76 333.9 ±5.08 47.9 ±2.76
304 22 86.4 ±3.75 327.5 ±4.71 41.3 ±2.73
1178 23 79.9 ±5.04 320.5 ±5.04 38.3 ±3.04
2028 23 84.5 ±3.62 316.8 ±3.60 30.4a ±2.25
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Corrected body weight: terminal body weight at GD 20 minus Uterine weight
Net weight change from GD 6: Corrected body weight minus day 6 body weight - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment related decrease waere noted on feed consumption between days 6-10 G at all exposure levels teasted. Decteases in feed consumption continued between days 6-10 G at 304, 1178, and 2028 ppm. Feed consumption of all treated groups returend to control value during post-treatment period (days 16-20 G)
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- There were no abortions observed in any of the treated dose groups.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- The pre- and postimplantation loss was unaffected by treatment.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- In the study, there was one dam high-dose dam with total litter loss. This observation is considered as not treatment-related.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- In the study, there were no early or late resorptions observed.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- There were no dead fetuses found in the uterine.
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- There was a Caesarian section performed on GD 20.
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Details on maternal toxic effects:
No animals died and no treatment-related clinical signs were noted for the dams in the 99, 304 or 1178 ppm groups. Scant feces was noted in the 2028 ppm group throughout the exposure period (GD 6-15). Treatment-related decreases on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they occurred only during the first 2 days of exposure and returned to control values by the next weighing period. The body weight and feed consumption values returned to control values for all groups during the post exposure period (GD 16-20). At 1178 and 2028 ppm, treatment-related effects included losses in maternal body and/or decreased body weight gain throughout the exposure period (GD 6 - 16) and decreased corrected maternal body weight gain. The gross necropsy evaluations did not indicate any treatment-related effects and there were no treatment-related differences between the control and treated groups in any reproductive parameter. - Dose descriptor:
- LOEC
- Remarks:
- maternal toxicity
- Effect level:
- ca. 0.41 mg/L air (analytical)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Remarks:
- maternal toxicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Remarks on result:
- other: no adverse effects observed
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects on fetal body weight in males, females and both sexes combined at any dose level tested.
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- Reproductive parameters in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
--------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of litters No. of live fetuses per litter
[ppm], 6 h/day
------------------------------------------------------------------------------------------------------------------------------------
0 25 13.88
99 23 13.87
304 22 14.86
1178 23 13.70
2028 23 14.65
----------------------------------------------------------------------------------------------------------------------------------- - Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in the sex ratio observed at any dose group.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- The mean number of pups per litter and litter weight were unaffected by treatment.
- Changes in postnatal survival:
- no effects observed
- Description (incidence and severity):
- The pups were euthanised shortly after the Caesarian section.
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related increase were detected in the type of external, visceral, or skeletal malformations.
Spontaneous malformations detected in the study included duplicated hypothalamus in a control fetus, hydrocephaly in a fetus at 304 ppm and an omphalocele in one fetus and enlarged adrenal glands in two fetuses at 1178 ppm was not considered to be treatment related as at 2028 ppm no increase was observed. - Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The significant increase in skeletal developmental variations at 1178 ppm was not detected at 2028 ppm, the highest doese tested. The slightly, not statistically significant number of fetuses with partial or unossified sternebra at 304 ppm was not considered a result of treatment since no dose response was demonstrated.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- There were no visceral malformations observed in any of the dose groups.
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
Fetal body weight was not affected by exposure to MMA vapors. The fetal external, visceral and skeletal examinations did not show any treatment related effects. - Dose descriptor:
- NOAEC
- Remarks:
- fetotoxicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: corresponding to 2028 ppm; no substance related effects observed
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- teratogenicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: corresponding to 2028 ppm; no substance related effects observed
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Exposure by inhalation to methyl methacrylate concentrations up to 8.44 mg/L (2028 ppm) resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity.
- Executive summary:
In a developmental toxicity study on rats acc. OECD 414 by inhalation pregnant CRl: CD Br rats were exposed to methyl methacrylate at concentrations of 0 (control), 99, 304, 1178 and 2028 ppm on days 6-15 of gestation. A maternal no observed level was not demonstrated since losses in maternal body weight or decreases in maternal body weight gain and decreases in maternal feed consumption were noted at all exposure levels tested. No embryo or fetal toxicity was evident and no increase in the incidence of malformations or variations was noted at exposure levels up to the highest dose of 2028 ppm. Therefore toxicity to the conceptus was not evident even at exposure levels that resulted in overt maternal toxicity.
Mean measured concentrations (± SD) within the chambers for the 0, 100, 300, 1200 and 2000 ppm groups were 98.8 (±3.4), 304.4 (±9.1), 1178.1 (±69.1) and 2028.2 (±107.3) ppm, respectively.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Methyl methacrylate
- EC Number:
- 201-297-1
- EC Name:
- Methyl methacrylate
- Cas Number:
- 80-62-6
- Molecular formula:
- C5H8O2
- IUPAC Name:
- methyl 2-methylprop-2-enoate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Supplier: Rohm and Haas Company
- Purity= 99.9 %
Test animals
- Species:
- rat
Administration / exposure
- Analytical verification of doses or concentrations:
- yes
- Details on study design:
- .
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No treatment-related clinical signs were observed bevore, during, or after the exposures at any exposure levels tested.
The only clinical sign noted was a minimal (only noted once or twice in 6 of 7 affected females) increase in the incidence of scant feces at 2028 ppm. - Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- There were no test substance-related or spontaneous mortalities in any group.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment-related decreases on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they occurred only during the first 2 days of exposure and returned to control values by the next weighing period. In addition, maternal body weight gain over the entire treatment period (days 6-16 G) and corrected maternal body weight gain at 99 and 304 ppm were similar to the control values. The body weight and feed consumption values returned to control values for all groups during the post exposure period (GD 16-20). At 1178 and 2028 ppm, treatment-related effects included losses in maternal body and/or decreased body weight gain throughout the exposure period (GD 6 - 16) and decreased corrected maternal body weight gain (body weight gain minus gravid uterine weight).
Body weight during gestation in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Mean Body weight [g] ± SD
[ppm], 6 h/day on GD 0 on GD 6 on GD 8 on GD 10 on GD 13 on GD 16 on GD 20
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 244.7 ±3.13 285.6 ± 3.93 295.4 ±4.33 307.1 ±4.20 327.3 ±4.68 350.6 ±5.05 414.2 ±6.84
99 23 246.3 ±2.93 286.1 ± 3.56 289.9 ±4.01 304.8 ±3.99 325.4 ±4.31 351.8 ±4.72 416.6 ±6.87
304 22 248.7 ±2.62 286.2 ± 3.11 288.9 ±3.60 301.3 ±3.91 321.1 ±4.09 347.1 ±4.58 413.9 ±6.09
1178 23 244.9 ± 2.77 282.2 ± 3.53 278.1a ±3.96 289.0a ±3.94 308.3a ±4.04 334.6 ±4.88 400.4 ±6.80
2028 23 246.7 ± 2.85 286.4 ± 3.03 275.2a ±2.68 280.9a ±3.40 306.2a ±3.49 332.7a ±4.27 401.3 ±5.56
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Change in weight during gestation in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Mean body weight gain ± SD on GD [g]
[ppm], 6 h/day on GD 0 - 6 on GD 6 - 8 on GD 8 - 10 on GD 10-13 on GD 13-16 on GD 6-16 on GD 16-20
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 41.0 ±1.86 9.8 ±0.83 11.6 ±0.58 20.3 ±0.94 23.2 ±1.76 65.0 ±2.33 63.6 ±2.75
99 23 39.7 ±2.36 3.8a ±1.39 15.0 ±1.90 20.5 ±1.28 26.4 ±1.52 65.7 ±2.83 64.8 ±3.81
304 22 37.5 ±2.05 2.7a ±1.09 12.4 ±1.09 19.8 ±1.04 26.0 ±1.30 60.9 ±2.62 66.8 ±2.54
1178 23 37.3 ±1.91 -4.1a ±-1.41 10.9 ±0.91 19.3 ±1.09 26.3 ±1.76 52.4a ±2.56 65.8 ±3.15
2028 23 39.7 ±1.08 -11.2a ±0.88 5.7a ±2.24 25.4a ±1.62 26.5 ±1.99 46.4a ±2.35 68.6 ±2.12
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Summary of Uterine and Net body weights in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of dams Gravid Uterus weight ± SD [g] Corrected Mean body weight ± SD on GD 20 [g] Net weight change ± SD from GD 6 [g]
[ppm], 6 h/day
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
0 25 82.7 ±3.81 331.5 ±4.77 45.8 ±2.21
99 23 82.7±5.76 333.9 ±5.08 47.9 ±2.76
304 22 86.4 ±3.75 327.5 ±4.71 41.3 ±2.73
1178 23 79.9 ±5.04 320.5 ±5.04 38.3 ±3.04
2028 23 84.5 ±3.62 316.8 ±3.60 30.4a ±2.25
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
a Denote significant differences from the control (0 ppm), p < 0.05, respectively.
Corrected body weight: terminal body weight at GD 20 minus Uterine weight
Net weight change from GD 6: Corrected body weight minus day 6 body weight - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment related decrease waere noted on feed consumption between days 6-10 G at all exposure levels teasted. Decteases in feed consumption continued between days 6-10 G at 304, 1178, and 2028 ppm. Feed consumption of all treated groups returend to control value during post-treatment period (days 16-20 G)
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- There were no abortions observed in any of the treated dose groups.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- The pre- and postimplantation loss was unaffected by treatment.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- In the study, there was one dam high-dose dam with total litter loss. This observation is considered as not treatment-related.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- In the study, there were no early or late resorptions observed.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- There were no dead fetuses found in the uterine.
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- There was a Caesarian section performed on GD 20.
- Changes in number of pregnant:
- no effects observed
- Details on maternal toxic effects:
- Details on maternal toxic effects:
No animals died and no treatment-related clinical signs were noted for the dams in the 99, 304 or 1178 ppm groups. Scant feces was noted in the 2028 ppm group throughout the exposure period (GD 6-15). Treatment-related decreases on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they occurred only during the first 2 days of exposure and returned to control values by the next weighing period. The body weight and feed consumption values returned to control values for all groups during the post exposure period (GD 16-20). At 1178 and 2028 ppm, treatment-related effects included losses in maternal body and/or decreased body weight gain throughout the exposure period (GD 6 - 16) and decreased corrected maternal body weight gain. The gross necropsy evaluations did not indicate any treatment-related effects and there were no treatment-related differences between the control and treated groups in any reproductive parameter.
Effect levels (maternal animals)
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- Dose descriptor:
- LOEC
- Remarks:
- maternal toxicity
- Effect level:
- ca. 0.41 mg/L air (analytical)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Remarks:
- maternal toxicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Remarks on result:
- other: no adverse effects observed
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects on fetal body weight in males, females and both sexes combined at any dose level tested.
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- Reproductive parameters in rats inhaling Methyl methacrylate on days 6 to 15 of gestation and euthanized on day 20:
--------------------------------------------------------------------------------------------------------------------------------------
Concentrations No of litters No. of live fetuses per litter
[ppm], 6 h/day
------------------------------------------------------------------------------------------------------------------------------------
0 25 13.88
99 23 13.87
304 22 14.86
1178 23 13.70
2028 23 14.65
----------------------------------------------------------------------------------------------------------------------------------- - Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in the sex ratio observed at any dose group.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- The mean number of pups per litter and litter weight were unaffected by treatment.
- Changes in postnatal survival:
- no effects observed
- Description (incidence and severity):
- The pups were euthanised shortly after the Caesarian section.
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related increase were detected in the type of external, visceral, or skeletal malformations.
Spontaneous malformations detected in the study included duplicated hypothalamus in a control fetus, hydrocephaly in a fetus at 304 ppm and an omphalocele in one fetus and enlarged adrenal glands in two fetuses at 1178 ppm was not considered to be treatment related as at 2028 ppm no increase was observed. - Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The significant increase in skeletal developmental variations at 1178 ppm was not detected at 2028 ppm, the highest doese tested. The slightly, not statistically significant number of fetuses with partial or unossified sternebra at 304 ppm was not considered a result of treatment since no dose response was demonstrated.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- There were no visceral malformations observed in any of the dose groups.
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
Fetal body weight was not affected by exposure to MMA vapors. The fetal external, visceral and skeletal examinations did not show any treatment related effects.
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEC
- Remarks:
- fetotoxicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: corresponding to 2028 ppm; no substance related effects observed
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- teratogenicity
- Effect level:
- 8.44 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: corresponding to 2028 ppm; no substance related effects observed
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Mean measured concentrations (± SD) within the chambers for the 0, 100, 300, 1200 and 2000 ppm groups were 98.8 (±3.4), 304.4 (±9.1), 1178.1 (±69.1) and 2028.2 (±107.3) ppm, respectively.
Applicant's summary and conclusion
- Conclusions:
- Exposure by inhalation to methyl methacrylate concentrations up to 8.44 mg/L (2028 ppm) resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity.
- Executive summary:
In a developmental toxicity study on rats acc. OECD 414 by inhalation pregnant CRl: CD Br rats rats were exposed to methyl methacrylate at concentrations of 0 (control), 99, 304, 1178 and 2028 ppm on days 6-15 of gestation. A maternal no observed level was not demonstrated since losses in maternal body weight or decreases in maternal body weight gain and decreases in maternal feed consumption were noted at all exposure levels tested. No embryo or fetal toxicity was evodent and no increase in the incidence of malformations or variations was noted at exposure levels up to the highest dose of 2028 ppm. Therefore toxicity to the conceptus was not evident even at expsoure levels that resulted in overt maternal toxicity.
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