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EC number: 202-613-0 | CAS number: 97-86-9
- 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study was conducted in accordance with a recognized scientific procedure for determining the developmental toxicity of a test substance when administered repeatedly via inhalation. Study was conducted incompliance with GLP regulations. The study meets national and international scientific standards (OECD 414) and provides sufficient information to support the conclusions regarding the NOAEL and the LOAEL demonstrated from the study data.
Data source
Reference
- Reference Type:
- publication
- Title:
- Developmental toxicities of methacrylic acid, ethyl methacrylate, n-butyl methacrylate, and allyl methacrylate in rats following inhalation exposure.
- Author:
- Saillenfait AM, Bonnet P, Gallissot F, Peltier A, Fabries JF
- Year:
- 1 999
- Bibliographic source:
- Toxicol Sci 50: 136-145
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Butyl methacrylate
- EC Number:
- 202-615-1
- EC Name:
- Butyl methacrylate
- Cas Number:
- 97-88-1
- Molecular formula:
- C8H14O2
- IUPAC Name:
- butyl methacrylate
- Details on test material:
- - Supplier : Fluka Chemie AG
- Name of test material (as cited in study report): n-butyl methacrylate
- Analytical purity: 99%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: IFFA CREDO, Saint Germain sur l'Arbresle, France
- Age at study initiation: sexually mature females, age not specified
- Weight at study initiation: 180-200 grams
- Housing: singly in polycarbonate cages
- Diet (e.g. ad libitum): UAR, Villemoisson, France
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Exposures were conducted in 200-L glass/stainless-steel inhalation chambers with dynamic and adjustable laminar air flow (6±20 m3/h). In order to prevent any leakage of the test atmospheres, the chambers were maintained at a negative pressure of no more than 3-mm water. The chamber temperature was set at 23 +/- 2°C and the relative humidity at 50 +/- 5%. Food and water were withheld during exposures.
The system used for vapor generation consisted in delivering a constant rate of liquid chemical with an infusion pump at the top of a heated glass column filled with glass beads. Compressed air heated by a glass heater was introduced at the bottom of the glass column in a countercurrent fashion to the liquid flow , an additional air flow rate was passed through the fritted disk of a heated bubbler containing the test chemical. The vaporized compounds were introduced into the main air-inlet pipe of the exposure chambers. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations were monitored continuously with a gas chromatograph equipped with a flame ionization detector and an automatic gas-sampling valve. In addition, the exposure levels were determined once during each 6-h exposure period by collecting atmosphere samples through glass tubes packed with activated charcoal. The charcoal samples were then desorbed with carbon disulide. The resulting samples were then analyzed by gas chromatography using appropriate interval standards.
- Details on mating procedure:
- Alter 2 weeks of acclimatization, nulliparous female rats were housed overnight with adult males (1 male:2 or 3 females) from the same strain and supplier. The day that vaginal smears were found to be sperm-positive was considered day 0 of gestation (GD). Mated females were randomly assigned to treatment groups using a randomization system stratified by body weight on GD 0
- Duration of treatment / exposure:
- days 6 - 20 of gestation
- Frequency of treatment:
- 6 hours per day
- Duration of test:
- On GD 21, the females were sacrificed
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Remarks:
- control
- Dose / conc.:
- 100 ppm
- Remarks:
- test material
- Dose / conc.:
- 300 ppm
- Remarks:
- test material
- Dose / conc.:
- 600 ppm
- Remarks:
- test material
- Dose / conc.:
- 1 200 ppm
- Remarks:
- test material
- No. of animals per sex per dose:
- 22-25 pregnant females per dose
- Control animals:
- other: yes, concurrently to filtered air
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: Maternal body weights were recorded on GDs 0, 6, 13, and 21.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Food consumption was measured for the intervals GDs 6-13 and 13-21
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: no data - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number of death and live fetuses: Yes - Fetal examinations:
- - External examinations: Yes: All live fetuses were weighed, sexed, and examined for external anomalies including those of the oral cavity
- Soft tissue examinations: Yes: Half of the live fetuses from each lifter were preserved in Bouin's solution and examined for internai soft-tissue changes (Barrow and Taylor, 1969; Wilson, 1965).
- Skeletal examinations: Yes: Half of the live fetuses from each lifte were fixed in ethanol (70%), eviscerated, and then processed for skeletal staining with alizarin red S for subsequent skeletal examination (Staples and Schnell, 1964).
- Head examinations: No data - Statistics:
- The number of CL, implantation sites, and live fetuses, maternal food consumption and various body weights were analyzed by ANOVA, followed by Dunnett'st-test. the percentage of non-live implant, resorptions,and males and the proportion of fetuses with alterations ineach litter were evaluated by Kruskal-Walles test followed by Dixon-Massey test. Rates of pregnancy and percentage of litters with any malformations or external, visceral, or skeletal variations were analyzed using Fisher's test. Where appropriate, least squares analysis was performed. The level of significance was p < 0.05.
- Indices:
- FERTILITY AND REPRODUCTIVE PERFORMANCE: The following data were recorded for each group of numbers of CL, and implantation sites
- number of resorptions and viable and dead fetuses.
- mean fetal body weights
- fetuses examined for gross malformations and skeletal abnormalities of sex and of fetuses. - Historical control data:
- no data
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
No test dam died. Exposure to 300 ppm or higher concentrations of n-butyl methacrylate led to a significant decrease in maternal body weight gain during the first half of exposure (Table 1). The overall maternal weight gain during GDs 6-21 and the absolute weight gain were significantly less than control at 1200 ppm. A slight reduction in maternal food consumption was observed during the first half of exposure at 300 ppm and higher concentrations (p < 0.05 and p <0.01 at 300 and 1200 ppm, respectively). No adverse effects on the average number of implantations and live fetuses, incidence of non-live implants or resorptions, or fetal sex ratio were noted among litters exposed to n-butyl methacrylate (Table 2).
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 100 ppm
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Fetal body weight was significantly reduced at 600 ppm (females) and at 1200 ppm (all, male and female fetuses). These decreases amounted to 5% of the concurrent control values at 1200 ppm. Occasional visceral malformations occurred in low frequency and were distributed across the different groups, including control (Table 3). There were no significant differences between the control and treated groups in the incidences of either individual or total external and visceral variations, or of individual skeletal variations. The only statistically significant changes were higher mean percentages of fetuses with skeletal variations or any variations at the highest concentration of n-butyl methacrylate, compared with the concurrent control. The biological relevance of these findings is limited by the fact that the observed incidences occurred with no clear concentration-related pattern. These increases might be considered at most as slight fetotoxicity.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 ppm
- Based on:
- test mat.
- Basis for effect level:
- fetal/pup body weight changes
- Dose descriptor:
- NOAEL
- Effect level:
- 600 ppm
- Based on:
- test mat.
- Basis for effect level:
- other: skeletal variations
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
TABLE 1
Change in Weight During Gestation in Sprague-Dawley Rats Inhaling n-Butyl Methacrylate on Days 6 to 20 of Gestation and Euthanized on Day 21
Concentration ppm/6 h/day |
No. of damsa |
Body weight (g) on GD 6 |
Body weightgain (g) on GD |
Absolute weight gain (g)b |
||
6±13 |
13±21 |
6±21 |
||||
0 |
24 |
257 ± 15 |
33 ± 6 |
100± 16 |
133 ± 19 |
27 ± 10 |
100 |
24 |
259 ± 16 |
31 ± 8 |
100± 15 |
132 ± 18 |
26 ± 8 |
300 |
25 |
258 ± 15 |
27 ±6** |
106± 12 |
132 ± 14 |
25 ± 9 |
600 |
22 |
264 ± 18 |
26 ± 5** |
102± 19 |
128 ± 19 |
21 ± 10 |
1200 |
25 |
261 ± 18 |
21 ± 6** |
98 ± 13 |
119 ± 15* |
19 ± 9** |
Note.Values are expressed as means ± SD.
a Includes all dams pregnant at euthanization.
bDay 21 body weight) 2 (gravid uterus weight) 2 (Day 6 body weight).
*,** Denote signi®cant differences from the control (0 ppm) value,p , 0.05 and p , 0.01, respectively.
TABLE 2
Reproductive Parameters in Sprague-Dawley Rats Inhaling Methacrylic
Acid, Ethyl Methacrylate, n-Butyl Methacrylate, or Allyl Methacrylate
on Days 6 to 20 of Gestation and Euthanized on Day 21
Concentration (ppm/6 h/day) |
Test animals (dams) |
Litters with implants |
Litters with live fetuses |
|
||||||||||
No. dead/ no. treated |
% of females pregnant at euthanization |
|||||||||||||
No. of litters |
No. of corpora lutes per dam |
No. of implantation sites per litter |
% of nonlive implants per littera |
% of resorption sites per litter |
No. of litters |
No. of live fetuses per litter |
% of males per litter |
Average fetal body weight (g) per litter |
||||||
All |
Males |
Females |
|
|||||||||||
0 |
0/26 |
92.3 |
24 |
15.63 ± 1.69 |
14.63 ±2.43 |
7.12 ± 12.12 |
6.52 ± 9.66 |
24 |
13.75 ± 3.01 |
53.40 ± 16.29 |
5.70±0.26 |
5.84 ± 0.29 |
5.54 ± 0.25 |
|
100 |
0/26 |
92.3 |
24 |
15.75 ± 1.45 |
14.71 ± 1.90 |
4.00 ± 6.80 |
4.00 ± 6.80 |
24 |
14.13 ± 2.11 |
51.50 ± 15.16 |
5.59± 0.25 |
5.71 ± 0.28 |
5.47 ± 0.27 |
|
300 |
0/26 |
96.2 |
25 |
16.12 ± 1.56 |
15.24 ± 1.59 |
4.05 ± 3.89 |
4.05 ± 3.89 |
25 |
14.60 ± 1.38 |
52.83 ± 12.70 |
5.53± 0.24 |
5.67 ± 0.26 |
5.38 ± 0.20 |
|
600 |
0/26 |
84.6 |
22 |
16.27 ± 1.52 |
15.18 ±2.54 |
5.28 ±8.08 |
5.28 ± 8.08 |
22 |
14.50 ± 3.02 |
46.59 ± 11.86 |
5.51± 0.33 |
5.72 ± 0.36 |
5.33 ± 0.35* |
|
1200 |
0/27 |
92.6 |
25 |
16.76 ± 3.30 |
15.08 ± 2.00 |
6.27 ± 6.08 |
6.27 ± 6.08 |
25 |
14.12 ± 1.99 |
46.22 ± 15.16 |
5.40± 0.24** |
5.56 ± 0.29** |
5.26 ± 0.24** |
|
aResorptions plus dead fetuses.
Values are expressed as means±SD.
*,** denote significant differences from the control (0 ppm) value,p , 0.05 and p , 0.01, respectively.
Applicant's summary and conclusion
- Conclusions:
- In a valid guideline study, n-BMA resulted in fetal toxicity, but no teratogenicity, at concentrations that also produced maternal toxicity.
- Executive summary:
In a study comparable to the OECD guideline # 414, groups of 22-25 pregnant female rats were given whole-body inhalation exposures to n-BMA at target concentrations of 0, 100, 300, 600 or 1200 ppm (analytical concentrations: 0, 99.6 +/- 5.0, 301.6 +/- 12.2, 602.3 +/-38.0, 1206.4 +/- 46.9 ppm) for 6 hr/day, during days 6 to 20 of gestation (GD). Maternal toxicity (decreased body weight gain) was shown at 300 to 1200 ppm. Feed consumption was decreased at 1200 ppm. No dam died during the test and there were no adverse effects on the average number of implantations and live fetuses, incidence of non-live fetuses, or on resorptions. Fetal body weights of male pups were significantly reduced at 1200 ppm, and females at 600 and 1200 ppm n-BMA. There were no significant differences between control and treated groups for external, visceral, or skeletal malformations. A significant increase in the skeletal variations per litter occurred at 1200 ppm n-BMA, compared to controls. The authors concluded that NOAEL for developmental toxicity was 300 ppm n-BMA. There was no evidence of embryolethality or teratogenicity with n-BMA.
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