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EC number: 240-815-0 | CAS number: 16752-77-5
- 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
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- Water solubility
- Solubility in organic solvents / fat solubility
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- 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
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- Endpoint summary
- Stability
- Biodegradation
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- 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

Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japan Ministry of Agriculture, Forestry and Fisheries Testing Guidelines for Toxicology Studies, 59 NohSan No. 4200
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Methomyl
- EC Number:
- 240-815-0
- EC Name:
- Methomyl
- Cas Number:
- 16752-77-5
- Molecular formula:
- C5H10N2O2S
- IUPAC Name:
- (E)-[1-(methylsulfanyl)ethylidene]amino N-methylcarbamate
- Test material form:
- solid: crystalline
Constituent 1
- Specific details on test material used for the study:
- - Substance name: Methomyl technical
- Substance ID: DPX-X1179
- Lot#: X1179-394
- Purity: 98.35%
Test animals
- Species:
- mouse
- Strain:
- other: Crl:CD®-1(ICR)BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Inc., Raleigh, North Carolina
- Age at study initiation: 62 days
- Weight at study initiation: 29.1-36.0 g (males); 21.5-27.3 g (females)
- Assigned to test groups randomly: Yes
- Housing: Standard wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Humidity (%): 50 ± 10
- Photoperiod: 12-hour light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Sterile water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Solutions of the test substance in the vehicle were prepared at concentrations of 0.3, 0.6, and 1.2 mg/mL. Uniformity was maintained during dosing by constant stirring. Single acute doses of the appropriate solutions were administered by oral intubation at 10 mL/kg yielding treatments of 3, 6, and 12 mg/kg bw.
The negative control (vehicle) was administered by gavage in a volume of 10 mL/kg. - Duration of treatment / exposure:
- Single oral dose
- Frequency of treatment:
- Single oral dose
Doses / concentrationsopen allclose all
- Dose / conc.:
- 3 mg/kg bw (total dose)
- Dose / conc.:
- 6 mg/kg bw (total dose)
- Dose / conc.:
- 12 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 5 (solvent control; 3, 6 mg/kg; positive control) and 6 (12 mg/kg)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CP)
- Route of administration: Oral intubation
- Doses / concentrations: 40 mg/kg
Examinations
- Tissues and cell types examined:
- bone marrow cells
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Based on the results from the range finding study, a dose of 12 mg/kg was selected as the maximum dose for both male and female mice
SAMPLING TIMES: 24, 48, and 72 hours
DETAILS OF SLIDE PREPARATION: Immediately after sacrifice, marrow from both femurs of each animal was aspirated and flushed into approximately 2 mL prewarmed (37°C) fetal bovine serum. The marrow was collected by centrifugation. Most of the supernatant was removed, and the cells were resuspended in the remaining 1-2 drops of serum. A Miniprep® automatic blood smearing instrument was used to prepare marrow smears. At least 3 slides per animal were prepared and fixed in absolute methanol for 8 mins. Slides were stained for 2.5 mins in 0.0125 mg/mL acridine orange in phosphate buffer (pH 7.4). Prior to scoring, a coverslip was floated on each slide using phosphate buffer.
METHOD OF ANALYSIS: Representative slides from each animal were examined blindly using incident light fluorescence microscopy. Only cells with good morphology and staining were scored. Colour was used to distinguish PCEs (reddish) from NCEs (dark green). PCEs (2000 per animal) were scored for the presence of micronuclei (round, bright yellow-green fluorescing bodies). Cellular inclusions that were irregularly shaped or stained, or out of the focal plane of the cell were considered artifacts. The unit of scoring was the micronucleated cell; PCEs with more than one micronucleus were scored as a single micronucleated PCE (MNPCE). Micronucleated NCEs seen in the optic fields scored to obtain 2000 PCEs were also counted. Additionally, the number of PCEs among 1000 erythrocytes was recorded for each animal. - Statistics:
- Data for the proportion of MNPCEs among 2000 PCEs and the proportion of PCEs among 1000 erythrocytes were transformed prior to analysis using the arcsin square root function. Transformed data for PCE or MNPCE frequencies were analyzed separately for normality of distribution using the Shapiro-Wilkes test. If results indicated that the transformed values for PCE or MNPCE frequencies were normally distributed in both sexes, parametric methods (viz., Analysis of Variance and Dunnett test) were used. If there was nonnormality in either sex, nonparametric methods (viz., Krushkal-Wallis test and Mann-Whitney U tests) were used for that variable using nontransformed proportions. Positive indicator data were not included in evaluating normality of distribution. Weight gain data were assumed to be normally distributed and were analyzed by ANOVA. Data from each sex and sacrifice time were analyzed separately, and individual comparisons to the control were made using each animal as the experimental unit. All analyses were conducted at a significance level of 5%. Positive indicator data were analyzed separately.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- 1 female mouse at 12 mg/kg was found dead ~24 h after dosing. Hyperactivity was displayed by 1 male at same dose. Lethargy was seen at 6 mg/kg in 3 males and at 12 mg/kg in 1 male and 1 female mice. One of these mice had half shut eyes 24 h post-dosing.
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY FOR DOSE SELECTION
- Dose range: 5 to 40 mg/kg
- Clinical signs of toxicity in test animals: Deaths occurred at 15 mg/kg (1/4 males, 0/4 females), 20 mg/kg (3/5 males, 2/6 females), 25 mg/kg (2/2 females), 30 mg/kg (4/5 males, 7/7 females), and 40 mg/kg (3/3 males, 3/3 females). Animals dosed at 20, 25, 30, and 40 mg/kg exhibited tremors, convulsions, and/or gasping within 30 minutes post-exposure. These symptoms lasted up to approximately seven minutes until the animals either died or recovered. Surviving animals then became lethargic and quiet. By 3 hours post-dosing, no signs of toxicity were observed. At 15 mg/kg, the surviving mice were lethargic and had shallow respiration immediately following dosing which subsided within the following hour. No deaths or clinical signs were observed at 5 or 10 mg/kg.
Any other information on results incl. tables
Table-1: PCE Frequency
Test substance (mg/kg) |
Sampling time (hrs) |
Sex |
N |
Mean %PCE (95% conf. limits) (determined on transformed values) |
Mean PCE/NCE ratio (SEM) |
0 |
24 |
M |
5 |
56.3 (44.0, 68.2) |
1.38 (0.24) |
0 |
24 |
F |
5 |
56.4 (48.1, 64.6) |
1.35 (0.20) |
3 |
24 |
M |
5 |
61.2 (55.9, 66.3) |
1.60 (0.12) |
3 |
24 |
F |
5 |
59.4 (47.3, 70.8) |
1.58 (0.33) |
6 |
24 |
M |
5 |
57.4 (43.2, 70.9) |
1.51 (0.41) |
6 |
24 |
F |
5 |
52.1 (48.1, 56.2) |
1.10 (0.06) |
12 |
24 |
M |
6 |
45.0 (38.3, 51.7) |
0.84 (0.08) |
12 |
24 |
F |
5a |
53.1 (48.7, 57.6) |
1.14 (0.08) |
0 |
48 |
M |
5 |
47.1 (41.6, 52.6) |
0.90 (0.07) |
0 |
48 |
F |
5 |
53.0 (45.8, 60.2) |
1.16 (0.14) |
3 |
48 |
M |
5 |
47.3 (39.3, 55.3) |
0.92 (0.11) |
3 |
48 |
F |
5 |
50.9 (39.2, 62.6) |
1.10 (0.19) |
6 |
48 |
M |
5 |
51.4 (41.6, 61.1) |
1.10 (0.15) |
6 |
48 |
F |
5 |
53.7 (47.4, 59.9) |
1.18 (0.11) |
12 |
48 |
M |
6 |
49.5 (40.2, 58.9) |
1.03 (0.15) |
12 |
48 |
F |
5b |
53.2 (49.9, 56.4) |
1.14 (0.05) |
0 |
72 |
M |
5 |
52.8 (43.8, 61.6) |
1.16 (0.17) |
0 |
72 |
F |
4b |
51.2 (43.6, 58.9) |
1.07 (0.09) |
3 |
72 |
M |
5 |
43.9 (35.7, 52.2) |
0.80 (0.10) |
3 |
72 |
F |
5 |
54.2 (45.7, 62.6) |
1.22 (0.15) |
6 |
72 |
M |
5 |
45.4 (30.6, 60.6) |
0.90 (0.18) |
6 |
72 |
F |
5 |
55.1 (45.4, 64.7) |
1.28 (0.18) |
12 |
72 |
M |
6 |
43.5 (40.0, 47.0) |
0.77 (0.04) |
12 |
72 |
F |
6 |
56.4 (52.2, 60.6) |
1.31 (0.09) |
CP, 40 |
24 |
M |
5 |
51.5 (48.6, 54.5) |
1.07 (0.05) |
CP, 40 |
24 |
F |
5 |
51.5 (42.9, 60.0) |
1.10 (0.15) |
a Mouse died prior to scheduled sacrifice time
b Mouse was misdosed and died within 24 hours of dosing
Table-2: MNPCE Frequency
Test substance (mg/kg) |
Sampling time (hrs) |
Sex |
N |
%MNPCEs |
|
Mean (SEM) |
Median (IQR) |
||||
0 |
24 |
M |
5 |
0.22 (0.06) |
0.30 (0.25) |
0 |
24 |
F |
5 |
0.14 (0.03) |
0.15 (0.12) |
3 |
24 |
M |
5 |
0.32 (0.07) |
0.30 (0.25) |
3 |
24 |
F |
5 |
0.16 (0.08) |
0.15 (0.32) |
6 |
24 |
M |
5 |
0.30 (0.05) |
0.30 (0.20) |
6 |
24 |
F |
5 |
0.15 (0.02) |
0.15 (0.10) |
12 |
24 |
M |
6 |
0.20 (0.04) |
0.22 (0.14) |
12 |
24 |
F |
5a |
0.21 (0.06) |
0.20 (0.18) |
0 |
48 |
M |
5 |
0.14 (0.04) |
0.15 (0.18) |
0 |
48 |
F |
5 |
0.17 (0.03) |
0.15 (0.10) |
3 |
48 |
M |
5 |
0.18 (0.05) |
0.15 (0.18) |
3 |
48 |
F |
5 |
0.15 (0.06) |
0.15 (0.25) |
6 |
48 |
M |
5 |
0.18 (0.05) |
0.20 (0.20) |
6 |
48 |
F |
5 |
0.14 (0.05) |
0.15 (0.22) |
12 |
48 |
M |
6 |
0.17 (0.04) |
0.18 (0.19) |
12 |
48 |
F |
5b |
0.18 (0.06) |
0.10 (0.25) |
0 |
72 |
M |
5 |
0.16 (0.06) |
0.15 (0.22) |
0 |
72 |
F |
4b |
0.14 (0.04) |
0.12 (0.16) |
3 |
72 |
M |
5 |
0.11 (0.03) |
0.10 (0.12) |
3 |
72 |
F |
5 |
0.15 (0.03) |
0.15 (0.10) |
6 |
72 |
M |
5 |
0.10 (0.03) |
0.10 (0.10) |
6 |
72 |
F |
5 |
0.16 (0.04) |
0.15 (0.18) |
12 |
72 |
M |
6 |
0.13 (0.02) |
0.12 (0.11) |
12 |
72 |
F |
6 |
0.19 (0.04) |
0.18 (0.15) |
CP, 40 |
24 |
M |
5 |
1.97 (0.52) |
1.85 (2.05)* |
CP, 40 |
24 |
F |
5 |
2.07 (0.25) |
1.90 (0.92)* |
a Mouse died prior to scheduled sacrifice time
b Mouse was misdosed and died within 24 hours of dosing
* p ≤0.05
Applicant's summary and conclusion
- Conclusions:
- Negative in mouse bone marrow micronucleus assay
- Executive summary:
The test substance was evaluated for its ability to induce micronuclei in bone marrow polychromatic erythrocytes (PCEs) of mice. The study was conducted following OECD guideline 474 and U.S. EPA 84-2.
A single acute dose of 0, 3, 6, or 12 mg/kg was administered by oral intubation to groups of male and female mice. In the vehicle control and all test substance treated groups, bone marrow smears were prepared approximately 24, 48, and 72 hours after dosing. 2000 PCEs per animal were scored for micronuclei.
No statistically significant increases in the frequency of micronucleated PCEs were observed in test substance treated mice at any dose level or sampling time. In addition, no statistically significant depressions in the proportion of PCEs among 1000 erythrocytes were observed. In this assay, the test substance was negative.
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