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EC number: 630-324-3 | CAS number: 861229-15-4
- 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
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
- Study period:
- June 2, 1992 - September 9, 1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 1982
- Qualifier:
- according to guideline
- Guideline:
- other: EEC Annex V Committee (EEC 1984)
- Qualifier:
- according to guideline
- Guideline:
- other: JEPA/MITI joint directive (JEPA,MOHW,MITI 1987)
- Qualifier:
- according to guideline
- Guideline:
- other: Guideline of the JMOHW
- Version / remarks:
- JMOHW 1989
- Qualifier:
- according to guideline
- Guideline:
- other: US EPA TSCA
- Version / remarks:
- 1987
- GLP compliance:
- yes
- Type of assay:
- other: micronucleus test
Test material
- Reference substance name:
- 2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate
- EC Number:
- 630-324-3
- Cas Number:
- 861229-15-4
- Molecular formula:
- C18H27ClO3
- IUPAC Name:
- 2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River U.K. Limited, Margate,Kent, England
- Age at study initiation: approximately 35 days
- Weight at study initiation: 22-24 g
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: plastic disposable cages, sexes separated
- Diet: ad libitum, pelleted Biosure LAD 1 rodent diet
- Water: ad libitum, tap water
- Acclimation period:11 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%):
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12 h/ 12h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: methylcellulose
- Amount of vehicle (if gavage or dermal): 1% - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Suspensions/emulsions of MCPP-P 2-EHE were prepared in aquous 1 % methylcellulose on the morning of the test. - Duration of treatment / exposure:
- 24 h, 48 h and 72 h
- Frequency of treatment:
- single
Doses / concentrationsopen allclose all
- Dose / conc.:
- 320 mg/kg bw (total dose)
- Remarks:
- =16 mg/mL test item in suspension, preliminary test
- Dose / conc.:
- 800 mg/kg bw (total dose)
- Remarks:
- =40 mg/mL test item in suspension, preliminary test
- Dose / conc.:
- 1 600 mg/kg bw (total dose)
- Remarks:
- =80 mg/mL test item in suspension, preliminary test (Phase II)
- Dose / conc.:
- 2 000 mg/kg bw (total dose)
- Remarks:
- =100 mg/mL test item in suspension, preliminary test
- Dose / conc.:
- 2 500 mg/kg bw (total dose)
- Remarks:
- =125 mg/mL test item in suspension, preliminary test (Phase II)
- Dose / conc.:
- 3 128 mg/kg bw (total dose)
- Remarks:
- =156.4 mg/mL test item in suspension, preliminary test (Phase II)
- Dose / conc.:
- 5 000 mg/kg bw (total dose)
- Remarks:
- =250 mg/mL test item in suspension, preliminary test
- Dose / conc.:
- 782 mg/kg bw (total dose)
- Remarks:
- =39.1 mg/mL test item in suspension, micronucleus test
- Dose / conc.:
- 1 564 mg/kg bw (total dose)
- Remarks:
- =78.2 mg/mL test item in suspension, micronucleus test
- Dose / conc.:
- 3 128 mg/kg bw (total dose)
- Remarks:
- =156.4 mg/mL test item in suspension, micronucleus test
- No. of animals per sex per dose:
- 15 per sex and dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- mitomycin C
- Route of administration: oral, gavage
- Doses / concentrations: prepared as a solution in 0.9% saline at a concentration of 0.6 mg/mL (dose: 12 mg/kg bw)
Examinations
- Tissues and cell types examined:
- both femurs dissected and bone marrow used for smears
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: based on resulted from preliminary toxicity test
SAMPLING TIMES: 5 males and 5 females from dose group and negative control sacrificed 24, 48 and 72 h after dosing; positive control group 24 h after dosing
DETAILS OF SLIDE PREPARATION: direct bone marrow smear was made onto slide containing a drop of calf serum, one smear from each femur, after air-drying smears were stained and fixed in methanol (>10 min). The smears were air-dried and stained for 10 min in 10% Giemsa (prepared by 1:9 dilution of Gurr´s improved R66 Giemsa with distilled water). Following rinsing in distilled water and differentiation in buffered distilled water (pH 6.8), the smears were air-dried and mounted with coverslips using DPX.
METHOD OF ANALYSIS: The stained smears were examined by light microscopy to determine the incidence of micronucleated cells per 1000 polychromatic erythrocytes per animal.
- Evaluation criteria:
- Micronuclei are identified by the following criteria:
(i) large enough to discern morphological characteristics
(ii) should possess a generally rounded shape with a clearly defined outline
(iii) should be deeply stained and similar in colour to the nuclei of other cells-not black
(iv) should lie in the same focal plane as the cell
(v) lack internal structure i.e. they are pyknotic
(vi) there should be no micronucleus-line debris in the area surrounding the cell
The proportion of polychromatic erythrocytes for each animal was assessed by examination of at least 1000 erythrocytes. A record of the number of micronucleated normochromatic erythrocytes observed during this assessment was also kept as recommended by Schmid (Schmid 1976). A positive response is normally indicated by a substantial, dose-related and statistically significant increase of micronucleated polychromatic erythrocytes compared to the incidence for the concurrent vehicle control group. - Statistics:
- Non- parametric statistical methods, based on rank, are chosen for analysis of results. For comparison of an individual treated group with a concurrent control group, Wilcoxon´s sum of ranks test was used. For multiple group comparisons Kruskal-Wallis´ version of this test was used. Jonckheere´s test for trend was used to analyze for dose-effect relationships.
Results and discussion
Test resultsopen allclose all
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- at 24 h and 72 h sampling time
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks:
- Mitomycin C caused large, highly significant increases in the frequency of mirconucleated polychromatic erythrocytes
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- at 48 h sampling time after re-examination of slides
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks:
- Mitomycin C caused large, highly significant increases in the frequency of mirconucleated polychromatic erythrocytes
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 320, 800, 2000, 5000 mg/kg bw (Phase I); 1600, 2000, 2500, 3128 mg/kg bw (Phase II)
- Clinical signs of toxicity in test animals:
phase I: after dosing piloerection was observed in all animals; at 2000 mg/kg animals showed in addition hunched posture and lethargy until approximatedy 24 h after dosing; at 5000 mg/kg bw mortality occured (3 animals out of 4 died) and animals showed increased respiratory rate, piloerection, hunched posture and lethargy
phase II: no mortality occured, moderate piloerection was observed in all animals directly after dosing, at 2500 and 3128 mg/kg bw animals showed lethargy, hunched posture, twitching, staggering gait, ptosis and increased respiratory rate
- Other: 3128 mg/kg bw was the maximum tolerated dose and chosen as highest dose in the micronulceus test
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei:
MCPP-p 2EHE did neither cause any substantial increases in micronucleated polychromatic erythrocyte counts (mnp) nor of micronucleated normochromatic erythrocytes (mnn) at any sampling time. The test item failed to cause any significant decreases in the proportion of polychromatic erythrocytes.
OTHER
- Chemical analysis by high performance liquid chromatography using ultraviolet detection proved the stability and homogeneity of MCPP-p 2EHE in the vehicle. In addition, it was confirmed that the dose formulations were accurately prepared and the mean result was within +4% of the nominal concentration.
Any other information on results incl. tables
Table 1 Summary of results - group totals/means for the entire experiment and results of statistical analysis
Sampling time |
Treatment |
Dose (mg/kg bw) |
p/p + n (mean %)C |
Incidence mnp (mean %)A |
Incidence mnn (total %) |
24 hours |
Vehicle control
MCPP-P 2-EHE
Mitomycin C |
-
782 1564 3128
12 |
52
51 ns 49 ns 49 ns
40 ** |
0.03
0.10 ns 0.07 ns 0.08 ns
4.66 ** |
0.00
0.04 0.00 0.00
0.09 |
48 hours |
Vehicle control
MCPP-P 2-EHE |
-
782 1564 3128
|
50
51 ns 51 ns 43 ns |
0.03
0.09 ns 0.10 ns 0.17 * (j) |
0.04
0.00 0.04 0.07 |
48 hours re-examination
24 hours re-examination |
Vehicle control
MCPP-P 2-EHE
Mitomycin CB |
-
782 1564 3128
12 |
not examined |
0.01
0.13 ns 0.14 ns 0.13 ns (j)
4.38 |
not examined |
72 hours |
Vehicle control
MCPP-P 2-EHE |
-
782 1564 3128
|
54
52 ns 54 ns 55 ns |
0.07
0.06 ns 0.04 ns 0.15 ns |
0.06
0.00 0.02 0.04 |
p/(p+n) % Proportion of polychromatic (immature) erythrocytes
mnp Number of micronucleated cells observed per 100 polychromatic erythrocytes
mnn Number of mirconucleated cells observed per 100 normochromatic erythrocytes (calculated total = number of mnn observed in the group / number of normochromatic erythrocytes examined X 100%)
A Results of statistical analysis using Kruskal-Wallis´, Jonckheere´s and Wilcoxon´s test as appropriate:
ns (P > 0.01), * (P< 0.01), ** P< (0.001) one-sided probabilities; j = result using Jonckheere´s test for trend only
B Positive control slides from the 24 hour time point were combined with slides from the 48 hour time point for examination by second slide reader
C Small apparent errors of ± 1% are due to rounding of individual values for presentation in tables
Applicant's summary and conclusion
- Conclusions:
- MCPP-P 2-EHE did not show any evidence of chromosome-damaging activity in the in vivo micronucleus assay.
- Executive summary:
An in vivo micronucleus test according to OECD TG 474 (Version 1982) and GLP was employed in male and female CD-1 mice to investigate a possible clastogenic or aneugenic effect in bone-marrow erythroblasts. Mice were administered by gavage single dosages of 782, 1564 or 3128 mg/kg bw. The negative control group received the vehicle (aqueous 1% methylcellulose) and the positive control group was treated with mitomycin C at 12 mg/kg bw. Bone marrow smears from five males and five females were obtained at three sampling times after dosing (24 h, 48 h and 72 h). One smear of each animal was examined for the presence of micronuclei in 1000 polychromatic erythrocytes. In addition, the proportion of polychromatic immature erythrocytes was assessed and the incidence of micronucleated normochromatic erythrocytes was recorded. Three male and four females died after treatment with the highest dose of MCPP-P 2-EHE in the micronucleus test, with non of these animals showing signs of misdosing.
At 24 h and 72 h, mice treated with MCPP-P 2-EHE did not show any significant increase in the frequency of micronucleated polychromatic erythrocytes. A significant increase was observed after 48 h. This increase was not confirmed in the re-examination of the slides and since all the original individual and mean values fell within the laboratory historical negative control range, it was concluded that the original increase was not treatment-related. The positive control mitomycin C induced a significant increase of micronucleated polychromatic erythrocytes and a decrease in the proportion of polychromatic erythrocytes. The negative control did not induce an increased frequency of micronucleated polychromatic erythrocytes. Therefore, MCPP-P 2-EHE has not shown any evidence of chromosome-damaging activity in the in vivo micronucleus assay.
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