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EC number: 807-448-3 | CAS number: -
- 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
Some information in this page has been claimed confidential.
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:
- 25 July 1995 and 17 August 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
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:
- 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
- Qualifier:
- according to guideline
- Guideline:
- other: Safepharm Standard Method Number EEC 29A
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Test material form:
- liquid
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 males weighed 23 to 30g and the females 20 to 24g, and were approximately 5 to 7 weeks old.
- Minimum acclimatisation period of 5 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 50 to 65%.
- 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:
- intraperitoneal
- Vehicle:
- Supplier's identification : Arachis oil
Supplier's batch number : 158
Saf-epharm serial number : CO/926
Date received : 7 June 1995
Description : straw coloured slightly viscous liquid
Storage conditions : room temperature - Details on exposure:
- Groups, each of ten mice (five males and five females), were dosed once only via the intraperitoneal route with test material at 37.5, 75 or 150 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. In addition three further groups of ten mice (five males and five females) were included in the study; two groups were given a single intraperitoneal 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, 37.5, 75, 150
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Supplier's identification : Cyclophosphamide
Supplier's lot number : 73HO846
Safepharm serial number : CO/911
Date received : 17 May 1995
Description : white powder
Storage conditions : 4°C
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 1000 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 positive response for bone marrow toxicity is demonstrated when the dose group mean polychromatic to normochromatic ratio is 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 lll (1989). The data was analysed following a*racine (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/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- clinical signs were observed in the RF study
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- 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 groups.
A positive mutagenic response is demonstrated when a statistically significant increase in the number of micronucleated polychromatic erythrocytes is observed for either the 24 or 48-hour kill times when compared to their corresponding control group.
If these criteria are not demonstrated, then the test material is considered to be non-genotoxic under the conditions of the test.
Any other information on results incl. tables
There was no significant increase in the frequency of micronucleated PCEs in any of the test material dose groups (37.5, 75 and 150 mg/kg) when compared to their concurrent vehicle control groups.
There was no statistically significant change in the PCE/NCE ratio in any of the test material dose groups when compared to their concurrent vehicle control groups. However, the presence of clinical signs and premature deaths in the range-finding toxicity study indicated that systemic absorption did occur. The steep toxicity curve seen in the range-finding study resulted in the selection of a maximum tolerated dose level that was expected to produce clinical signs in the main study. The absence of clinical signs in the main study was considered not to affect its integrity or validity.
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 of cyclophosphamide under the conditions of the test.
The test material was found not to produce a significant increase in the frequency of micronuclei in polychromatic erythrocytes of mice under the conditions of the test.
Applicant's summary and conclusion
- Conclusions:
- The genetic toxicity of the test material was assessed in accordance with OECD Guideline 474, Mammalian Erythrocyte Micronucleus Test. The test item was considered to be non-genotoxic under the conditions of the test.
- Executive summary:
A study was performed to assess the potential of the test material to produce damage to chromosomes or aneuploidy when administered via the intraperitoneal route to mice. The method followed was designed to comply with Method B12 of the EEC Commission Directive 92/69/EEC which constitutes Annex V of Council Directive 57/548/EEC.
Following a preliminary range-finding study to find a suitable dose level for the test material, the micronucleus study was conducted using the test material at the maximum tolerated dose level of 150 mg/kg with 75 and 37.5 mg/kg as the lower dose levels.
In the micronucleus study, groups of ten mice (five males and five females) were given a single intraperitoneal dose of the test material at 37.5, 75 or 150 mg/kg. Animals were killed 24 or 48 hours later, the bone marrow extracted and smear preparations made and stained. Polychromatic and normochromatic erythrocytes were scored for the presence of micronuclei.
Further groups of mice were dosed via the intraperitoneal route with arachis oil or orally with cyclophosphamide, to serve as vehicle and positive controls respectively.
There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with test material when compared to the concurrent vehicle control groups. No significant change in the PCE/NCE ratio was observed after dosing with the test material. Although, the presence of clinical signs and premature cleaths during the preliminary range-finding study would indicate systemic absorption had occurred.
The positive control material produced a marked increase in the frequency of micronucleated polychromatic erythrocytes.
The test material was considered to be non-genotoxic under the conditions of the test.
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