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Diss Factsheets
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EC number: 219-581-9 | CAS number: 2467-13-2
- 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)
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 September 2003 to 28 October 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: No deviations. Study done under GLP standards and performed according to Safepharm Standard Method Number that was designed to comply with Method B12 of the EEC Commission Directive 2000/32/EC and OECD test method 474.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 2003
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Test material form:
- other: colourless liquid
- Details on test material:
- Description: colourless liquid
Storage conditions: room temperature, in the dark, over silica gel, under nitrogen
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Sufficient male and female albino CD-1 Strain mice were supplied by Charles River (UK) Limited, Manston, Kent.
- At the start of the main study the mice weighed 26 to 30g, and were approximately 5 to 8 weeks old.
- Minimum acclimatisation period of 7 days.
- The animals were housed in groups of up to 5 in solid-floor polypropylene cages with woodflake bedding.
- Free access to mains drinking water and food.
- The animal room was maintained at a temperature of 19 to 25°C and relative humidity of 30 to 70%.
- The rate of air exchange was approximately 15 changes per hour.
- Lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Supplier's identification : Arachis oil
Supplier's batch number : T71
Safepharm serial number : V-2818 (V-2932 after drying)
Date received : 28 May 2003
Description : straw coloured slightly viscous liquid
Storage conditions : room temperature - Details on exposure:
- In a range-finding study, groups of 1 male and 1 female were dosed with 2000 or 1500 mg/kg. In the main study, groups, each of seven male mice, were dosed once only via the oral route with test material at 375, 750 or 1500 mg/kg. One group of mice from each dose group was killed by cervical dislocation 24 hours following treatment and a second at 48 hours (1500 mg/kg only). In addition three further groups of ten mice (five males and five females) were included in the study; two groups were given a single oral dose of the vehicle (arachis oil) and the third group was dosed orally with cyclophosphamide, a positive control material known to produce micronuclei under the conditions of the test. The vehicle control groups were killed 24 and 48 hours following dosing and positive control group animals were killed 24 hours following dosing.
- Duration of treatment / exposure:
- 24 and 48 hours
- Frequency of treatment:
- once
- Post exposure period:
- No
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 375, 750, 1500
Basis:
nominal conc.
- No. of animals per sex per dose:
- 7
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Supplier's identification : Cyclophosphamide
Supplier's lot number : 91K1176
Safepharm serial number : R-2827
Date received : 10 June 2003
Description : white powder
Storage conditions : 4°C in the dark
The concentration, homogeneity and stability of the positive control material and its preparation were not determined by analysis.
Examinations
- Tissues and cell types examined:
- Bone marrow polychromatic erythrocytes were examined for the presence or absence of micronuclei.
- Details of tissue and slide preparation:
- Immediately following sacrifice (ie. 24 or 48 hours following dosing), both femurs were dissected from each animal, aspirated with foetal calf serum
and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fixed in absolute methanol and stained in May-Grünwald/Giemsa, dried and coverslipped using mounting medium. - Evaluation criteria:
- Stained bone marrow smears were coded and examined ’blind’ using light microscopy at x1000 magnification. The incidence of micronucleated cells per 2000 polychromatic erythrocytes (PCE-blue stained immature cells) per animal was scored. Micronuclei are normally circular in shape, although occasionally they may be oval or half-moon shaped, and have a sharp contour with even staining. In addition, the number of normochromatic
erythrocytes (NCE-pink stained mature cells) associated with 1000 polychromatic erythrocytes was counted; these cells were also scored for
incidence of micronuclei.
The ratio of polychromatic to normochromatic erythrocytes was calculated together with appropriate group mean values for males and females
separately and combined. - Statistics:
- A comparison was made between the number of micronucleated polychromatic erythrocytes occurring in each of the test material groups and the number occurring in the corresponding vehicle control group.
A positive mutagenic response was demonstrated when a statistically significant, dose-responsive, toxicologically relevant increase in the number of micronucleated polychromatic erythrocytes was observed for either the 24 or 48-hour kill times when compared to their corresponding control group.
If these criteria were not fulfilled then the test material was considered to be non-genotoxic under the conditions of the test.
A positive response for bone marrow toxicity was demonstrated when the dose group mean polychromatic to normochromatic ratio was shown to be statistically significantly lower than the concurrent vehicle control group.
All data were statistically analysed using appropriate statistical methods as recommended by the UKEMS Sub-committee on Guidelines for Mutagenicity Testing Report, Part I11 (1989). The data was analysed following a ,/(x + 1) transformation using Student’s t-test (two tailed) and any significant results were confirmed using the one way analysis of variance.
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- clinical signs were observed
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
Any other information on results incl. tables
There
was a marked and statistically significant decrease in the PCE/NCE ratio
in the 48-hour 1500
mgkg test material group when compared to their concurrent vehicle
control group. This accompanied
with the clinical observations was taken to confrm that systemic
absorption had occurred,
and exposure to the target tissue achieved. There
were no statistically significant increases in the frequency of
micronucleated PCEs in any ofthe
test material dose groups when compared to their concurrent vehicle
control groups. The
positive control group showed a marked increase in the incidenceofmicronucleated
polychromatic
erythrocytes hence confirming the sensitivity of the system to the known mutagenic
activity ofcyclophosphamide under the conditions ofthe test. The
test material was found not to produce a significant increase in the
frequency of micronuclei in
polychromatic erythrocytes ofmice under the conditionsofthe
test.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The test substance was considered to be non-genotoxic under the conditions of the test. - Executive summary:
Introduction
The study was performed to assess the potential of the test material to produce damage to chromosomes or aneuploidy when administered to mice. The method was designed to comply with the 1997 OECD Guidelines for Testing of Chemicals No.474 "Micronucleus Test", Method B12 of the EC Commission Directive 2000/32/EC, the USA EPA, TSCA and FIFRA guidelines and the Japanese METL'MHLW guidelines for testing of new chemical substances.
MethodsThe range-finding test was performed to find suitable dose levels of the test material, route of administration and investigate to see if there was a marked difference in toxic response between the sexes. There was no marked difference in test material toxicity between the sexes; therefore the main study was performed using only male mice. The micronucleus test was conducted using the oral route in groups of seven mice (males) at the maximum tolerated dose (MTD) 1500 mgkg with 750 and 375 mgkg as the two lower dose levels. Animals were killed 24 or 48 hours later, the bone marrow was extracted, and smear preparations made and stained.
Polychromatic (PCE) and normochromatic (NCE) erythrocytes were scored for the presence of micronuclei. Further groups of mice were given a single oral dose of dried arachis oil (7mice) or dosed orally with cyclophosphamide (5 mice), to serve as vehicle and positive controls respectively. Vehicle control animals were killed 24 or 48 hours later, and positive control animals were killed after 24
hours.
ResultsA statistically significant decrease in the PCE/NCE ratio was observed in the 48-hour1500 mgkg test material dose group when compared to the concurrent control group. This and the presence of clinical signs were taken to indicate that systemic absorption had occurred and exposure ofthe target tissue achieved. There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test material when compared to the concurrent vehicle control groups. The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the sensitivity of the system to the known mutagenic activity ofcyclophosphamide under the conditionsofthe test.
ConclusionThe test material was considered to be non-genotoxic under the conditions of the test.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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