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EC number: 230-386-8 | CAS number: 7085-19-0
- 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 / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 June 2000 to 10 August 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.11 (Mutagenicity - In Vivo Mammalian Bone-Marrow Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: UKEMS Sub-Committee on Guidelines for Mutagenicity Testing, Report, Part 1 revised
- Version / remarks:
- Basic Mutagenicity Test: UKEMS recommended procedures, 1990
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: US, EPA, TSCA and FIFRA Guidelines
- Version / remarks:
- Not specified
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian bone marrow chromosome aberration test
Test material
- Reference substance name:
- Mecoprop
- EC Number:
- 230-386-8
- EC Name:
- Mecoprop
- Cas Number:
- 7085-19-0
- Molecular formula:
- C10H11ClO3
- IUPAC Name:
- 2-(4-chloro-2-methylphenoxy)propanoic acid
- Test material form:
- solid
- Remarks:
- Light brown
- Details on test material:
- Storage: Room temperature in the dark.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Approximately eight to ten weeks old.
- Weight at study initiation: 225 to 270g
- Assigned to test groups randomly: Yes. The animals were selected at random and given a number unique within the study by ear punching and a number written on a colour coded cage card.
- Housing: The animals were housed in groups of up to seven by sex in solid-floor polypropylene cages with woodflakes bedding.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Minimum acclimatisation period of seven days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): approximately fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): twelve hours light and twelve hours darkness.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: Arachis oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
For the purpose of this study the test material was freshly prepared as required as a suspension at the appropriate concentration in arachis oil.
- Dose volume: 10 mL/kg
- Concentration:
125 mg/L group: 12.5 mg/mL
250 mg/L group: 25 mg/mL
500 mg/L group: 50 mg/mL - Duration of treatment / exposure:
- Single oral administration
- Frequency of treatment:
- Once
- Post exposure period:
- The animals were sacrificed between 24 - 48 hours after test material administration.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle control
- Dose / conc.:
- 125 mg/kg bw/day (nominal)
- Remarks:
- Low dose
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- Mid dose
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- High dose
- No. of animals per sex per dose:
- Vehicle control: 14 males total (Kill Time 48 and 24 hours)
Positive control: 5 males
Test material low and mid dose: 7 males
Test material high dose: 14 males (Kill time 48 and 24 hours) - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide:
- Doses / concentrations: 25 mg/kg. The positive control material was freshly prepared as required as a solution at the appropriate concentration in distilled water.
Examinations
- Tissues and cell types examined:
- 100 metaphase cells of adequate quality were scored, if possible, from the slides prepared from each animal for both numerical and structural chromosome aberrations.
- Details of tissue and slide preparation:
- DOSE SELECTION RATIONALE:
A range-finding toxicity study was performed to determine a suitable dose level and route of administration for the chromosome aberration study. The dose level selected should ideally be the maximum tolerated dose level or that which produces some evidence of toxicity up to a maximum recommended dose of 2 000 mg/kg. The range-finding toxicity study was also used to determine if the main study was to be performed using both sexes or males only. Using toxicity data supplied by the sponsor it was considered unnecessary to investigate the intraperitoneal route. The supplied data also showed no marked differences between the sexes and therefore only male rats were used to determine the maximum tolerated dose level for use in the main study.
All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its bodyweight at the time of dosing.
Animals were observed one hour after dosing and subsequently once daily for two days. Any deaths and evidence of overt toxicity were recorded at each observation. No necropsies were performed.
In the main study, groups, each of seven rats, were dosed once only via the oral route with the test material at 125, 250 or 500 mg/kg. One group of rats from each dose level was killed by cervical dislocation 24 hours following treatment and a second group dosed at 500 mg/kg was killed after 48 hours. In addition, three further groups of rats were included in the study; two groups (seven rats) were dosed via the oral route with the vehicle alone (arachis oil) and a third group (five rats) was dosed orally with cyclophosphamide, a positive control material known to produce chromosome aberrations under the conditions of the test. The vehicle controls were killed 24 and 48 hours following treatment and positive control group animals were killed 24 hours following treatment.
All animals were observed for signs of overt toxicity and death one hour after dosing and then once daily as applicable and immediately prior to termination.
TREATMENT AND SAMPLING TIMES:
Animals were injected i.p. with a solution of colchicine at 4 mg/kg approximately 2 to 3 hours prior to bone marrow harvest. At the scheduled time, animals were killed by cervical dislocation and one femur was extracted from each animal and cleaned of muscle and connective tissue. The bone marrow was aspirated into 5 mL of Hank's balanced salt solution (HBSS) and spun down in a centrifuge. The supernatant was removed and the cell pellet resuspended in 0.075 M KCl at room temperature for 15 minutes (including five minutes centrifugation). The cells were recentrifuged and all but 1 mL of the supernatant removed. After resuspension of the cell pellet, the cells were fixed by the addition of freshly prepared fixative (methanol:glacial acetic acid, 3:1). The fixative was changed several times and the cells stored at 4 °C for at least 4 hours.
DETAILS OF SLIDE PREPARATION:
After storage the cell suspensions were recentrifuged and the fixative removed to leave a sufficient amount to give a milky suspension on resuspension of the cell pellet. A few drops of each cell suspension was dropped onto clean, wet slides and air-dried. When completely dry the slides were stained in 5 % Giemsa for 10 minutes and rinsed in tap water and distilled water. When dry the slides were coverslipped using a mounting medium.
Groups, each of seven rats, were dosed once only via the oral route with the test material at 125, 250 or 500 mg/kg. One group of rats from each dose level was killed by cervical dislocation 24 hours following treatment and a second group dosed at 500 mg/kg was killed after 48 hours. In addition, three further groups of rats were included in the study; two groups (seven rats) were dosed via the oral route with the vehicle alone (arachis oil) and a third group (five rats) was dosed orally with cyclophosphamide, a positive control material known to produce chromosome aberrations under the conditions of the test. The vehicle controls were killed 24 and 48 hours following treatment and positive control group animals were killed 24 hours following treatment. - Evaluation criteria:
- SLIDE EVALUATION
The stained slides were coded and examined 'blind' using light microscopy at x 100 and x 1 000 magnifications.
If the cell had 40 to 44 or more chromosomes, any gaps, breaks or rearrangements were noted according to the simplified system of Savage (1976) recommended in the 1990 UKEMS Guidelines for Mutagenicity Testing. Aberrations recorded by the slide scorers were checked by a Senior Cytogeneticist. - Statistics:
- Comparisons were made between the negative control groups and each corresponding treatment dose group, with a chi-squared test, using observed numbers of cells with aberrations.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
In animals dosed with test material via the oral route, clinical signs were observed at and above 500 mg/kg as follows: hunched posture, ataxia, lethargy, loss of righting reflex, decreased and laboured respiration, ptosis, pile-erection and splayed gait. When observations were made approximately 24 hours after dosing there was some concern with the condition of the animals dosed with 750 mg/kg. These animals were observed again at approximately 26 hours and, due to the severity of the toxicity of the test material, they were killed in extremis.
Adequate evidence of test material toxicity was demonstrated via the oral route of administration, therefore, this was selected for use in the main study. A maximum tolerated dose (MTD) of the test material, 500 mg/kg, was selected for use in the main study, with 125 and 250 mg/kg as the lower dose levels.
RESULTS OF DEFINITIVE STUDY
Evaluation of bone marrow slides:
- There were no clear statistically significant reductions in the mean mitotic index in any of the test material treatment groups when compared to their concurrent vehicle control groups. The mean mitotic index of the positive control group was sharply depressed compared to that of the 24-hour vehicle control group.
- All the negative control animals gave values of chromosome aberrations within the expected range. The mean frequency of cells with aberrations was consistent between the two vehicle control groups, the highest frequency (0.3 % cells with aberrations excluding gaps) being seen in the 24 hour group.
- The positive control group animals showed highly significant increases in the frequency of cells with aberrations indicating that the test method itself was operating as expected.
- The test material was seen to induce no significant, dose-related increases in the frequency of cells with aberrations in any of the treatment groups.
- The test material did not induce a significant increase in the numbers of polyploid cells in any of the treatment groups.
Historical Aberration Ranges for Vehicle and Untreated Control Cultures
Experiments with rat bone marrow cells have established a range of aberration frequencies acceptable for control animals, these are commonly in the range of 0 to 3 % cells with structural aberrations.
A positive response was recorded for a particular treatment if the % cells with aberrations markedly exceeded that seen in the concurrent control. For modest increases in aberration frequency, appropriate statistical tests may be applied in order to record a positive response.
Any other information on results incl. tables
Mortality and Clinical Results
There were no premature deaths seen in any of the dose groups. Clinical
signs were observed in animals dosed with the test material at and above
125 mg/kg in both the 24 and 48-hour groups where applicable, these were
as follows: lethargy, hunched posture, ataxia, decreased and laboured
respiration, ptosis, loss of righting reflex, splayed gait, stained
urine and diuresis. The severity of the clinical signs increased with
the increase in dose of the test material.
Group Mean Results of Chromosome Aberration Assay
Treatment Group |
Animals |
Numbers of Cells Scored |
Polyploid Cells |
Total Gaps |
Chromatid |
Chromosome |
Others |
Total Aberrations (+ Gaps) |
Total Aberrations (- Gaps) |
Cells with Aberrations (+ Gaps) |
Cells with Aberrations (- Gaps) |
||
Breaks |
Exchanges |
Breaks |
Exchanges |
||||||||||
Vehicle Control 48 hours |
Males |
700 |
1 (0.1) |
3 (0.4) |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
4 (0.6) |
1 (0.1) |
3 (0.4) |
1 (0.1) |
Vehicle Control 24 hours |
Males |
700 |
1 (0.1) |
1 (0.1) |
1 (0.1) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
0 (0.0) |
3 (0.4) |
2 (0.3) |
3 (0.4) |
2 (0.3) |
Positive Control |
Males |
500 |
0 (0.0) |
61 (12.2) |
71 (14.2) |
58 (11.6) |
20 (4.0) |
2 (0.4) |
16 (3.2) |
212 (42.4) |
151 (30.2) |
113 *** (22.6) |
94 *** (18.8) |
Test Material 500 mg/kg 48 Hours |
Males |
700 |
0 (0.0) |
2 (0.3) |
3 (0.4) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
0 (0.0) |
6 (0.9) |
4 (0.6) |
5 (0.7) |
3 (0.4) |
Test Material 500 mg/kg 24 Hours |
Males |
700 |
0 (0.0) |
5 (0.7) |
3 (0.4) |
0 (0.0) |
5 (0.7) |
0 (0.0) |
0 (0.0) |
13 (1.9) |
8 (1.1) |
9 (1.3) |
5 (0.7) |
Test Material 250 mg/kg 24 Hours |
Males |
700 |
1 (0.1) |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
Test Material 125 mg/kg 24 Hours |
Males |
700 |
1 (0.1) |
5 (0.7) |
2 (0.3) |
0 (0.0) |
1 (0.1) |
0 (0.0) |
0 (0.0) |
8 (1.1) |
3 (0.4) |
8 (1.1) |
3 (0.4) |
X = > 10 aberrations per cell (not included in total aberrations)
Figures in brackets = aberrations per 100 cells
*** = p < 0.001
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study the test material did not induce any significant increases in the frequency of chromosome aberrations in rat bone marrow under the conditions of the test. The test material was considered to be non-clastogenic to rat bone marrow cells in vivo.
- Executive summary:
The potential of the test material to produce damage to chromosomes or the mitotic apparatus when administered to rats was assessed according to OECD Test Guideline 475 and EU Method B.11, in compliance with GLP.
A range-finding study was performed to find suitable dose levels of the test material. Adequate oral toxicity data in rats was supplied by the sponsor which showed that there was no marked differences in test material toxicity between the sexes. Therefore, the main study was performed using only male rats. The chromosome aberration study was conducted using the oral route in groups of seven rats (males) at the maximum tolerated dose (MTD) 500 mg/kg with 250 and 150 mg/kg as the lower dose levels. Further groups of rats were given a single oral dose of arachis oil (7 rats) or dosed orally with cyclophosphamide (5 rats), to serve as vehicle and positive controls respectively. Animals were killed 24 or 48 hours later, the bone marrow extracted and slide preparations made and stained. Bone marrow cells were scored for the presence of chromosome aberrations.
No statistically significant decreases in the mitotic index mean values were observed in the 24 or 48 hour test material groups when compared to their concurrent vehicle control group. However, the observation of clinical signs indicated that systemic absorption, and consequently, exposure to the target tissue, had occurred.
There was no evidence of a statistically significant increase in the incidence of chromosome aberrations in animals dosed with the test material when compared to the concurrent vehicle control groups. The positive control material produced a marked increase in the frequency of chromosome aberrations.
Under the conditions of this study the test material did not induce any significant increases in the frequency of chromosome aberrations in rat bone marrow under the conditions of the test. The test material was considered to be non-clastogenic to rat bone marrow cells in vivo.
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