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EC number: 208-993-4 | CAS number: 551-16-6
- 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 vitro
Administrative data
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27 November 2009 to 12 February 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study conducted to current accepted guidelines
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
Test material
- Reference substance name:
- 6-aminopenicillanic acid
- EC Number:
- 208-993-4
- EC Name:
- 6-aminopenicillanic acid
- Cas Number:
- 551-16-6
- Molecular formula:
- C8H12N2O3S
- IUPAC Name:
- 6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
- Details on test material:
- - Name of test material : 6-Aminopenicillanic acid
- Substance type: Off white powder
- Physical state: Solid
- Analytical purity: 98.7 % (w/w)
- Impurities : Any other single impurity 0.07 %, Penicinic acid 0.17 %, Related Substance and Degradation Products 0.85 %
- Purity test date: 29 May 2009
- Lot/batch No.: 09X10247
- Expiration date of the lot/batch: 26 May 2011
- Storage condition of test material: Room temperature in the dark
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- lymphocytes: Collected from a human volunteer
- Details on mammalian cell type (if applicable):
- The volunteer had not been exposed to high levels of radiation or hazardous chemicals and had not knowingly recently suffered from a viral infection. The cell-cycle time for the lymphocytes from the donors used in this study was determined using BrdU (bromodeoxyuridine) incorporation to assess the number of first, second and third division metaphase cells to calculate the average generation time (AGT). The average AGT for the regular donors used in this laboratory has been determined to be approximately 17 hours under typical experimental exposure conditions.
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 microsomal enzyme fraction
- Test concentrations with justification for top dose:
- PRELIMINARY TEST
4(20)-hour without S9 (µg/mL) : 0, 8.44, 16.88, 33.75, 67.5, 135, 270, 540, 1080, 2160
4(20)-hour with S9 (µg/mL): 0, 8.44, 16.88, 33.75, 67.5, 135, 270, 540, 1080, 2160
24-hour without S9 (µg/mL): 0, 8.44, 16.88, 33.75, 67.5, 135, 270, 540, 1080, 2160
MAIN TEST
4(20)-hour without S9 (µg/mL) : 0, 67.5, 135, 270, 540, 1080, 2160, mitomycin C 0.4
4(20)-hour with S9 (µg/mL): 0, 67.5, 135, 270, 540, 1080, 2160, cyclophosphamide 5
24-hour without S9 (µg/mL): 0, 67.5, 135, 270, 540, 1080*, 2160, mitomycin C 0.2 - Vehicle / solvent:
- - Vehicle(s)/solvent: Minimal Essential Medium (MEM)
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- Migrated to IUCLID6: in the presence of S9
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- Migrated to IUCLID6: in the absence of S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 hours exposure in the absence of metabolic activation (S9), 4 hours in the presence of an induced rat liver homogenate metabolising system (S9), and a 24 hours continuous exposure in the absence of metabolic activation.
- Expression time (cells in growth medium): 20 hours
SPINDLE INHIBITOR (cytogenetic assays): demecolcine (Colcemid 0.1 µg/ml) was added two hours before the required harvest time
STAIN (for cytogenetic assays): 5% Gurrs Giemsa for 5 minutes
NUMBER OF REPLICATIONS: Performed in duplicate
NUMBER OF CELLS EVALUATED: In total 2000 lymphocyte cell nuclei
DETERMINATION OF CYTOTOXICITY
- Method: The slides were checked microscopically to determine the quality of the metaphases and also the toxicity
OTHER EXAMINATIONS:
- Determination of polyploidy: If greater than 44 chromosomes are scored and the number is a multiple of the haploid count then the cell is classified as a polyploid cell.
- Determination of endoreplication: If the chromosomes are arranged in closely apposed pairs, ie. 4 chromatids instead of 2, the cell is scored as endoreduplicated(E). - Evaluation criteria:
- The first 100 consecutive well-spread metaphases (where possible) from each culture were counted, where there were approximately 30 to 50% of cells with aberrations, slide evaluation was terminated at 50 cells. If the cell had 44-48 chromosomes, any gaps, breaks or rearrangements were noted according to the simplified system of Savage (1976) recommended in the 1983 UKEMS guidelines for mutagenicity testing.
The classification criteria is defined in the section Any other information on materials and methods incl. tables under the heading Classification Criteria. - Statistics:
- The frequency of cells with aberrations excluding gaps and the frequency of polyploid cells was compared, where necessary, with the concurrent vehicle control value using Fisher's Exact test.
Results and discussion
Test results
- Species / strain:
- lymphocytes: Human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: There was no significant change in pH when the test material was dosed into media
- Effects of osmolality: The osmolality did not increase by more than 50 mOsm
- Precipitation:. No precipitate was observed in the parallel blood-free cultures at the end of the exposure, at any dose level in any of the three exposure groups.
RANGE-FINDING/SCREENING STUDIES: Microscopic assessment of the slides prepared from the exposed cultures showed that metaphase cells were present up to 2160 µg/ml in all three of the exposure groups. The test material induced some evidence of toxicity in the 4(20)-hour exposure groups, and clear dose-related toxicity in the 24-hour continuous exposure group.
COMPARISON WITH HISTORICAL CONTROL DATA: In the 4(20)-hour exposure group in the absence of metabolic activation a very modest statistically significant increase in the frequency of cells with aberrations was recorded at the maximum dose level of 2160 µg/mL. The response which was only just outside the historical control range for this dose group, was compared to a low vehicle control value, did not include any exchange-type aberrations and was not reproduced in the 24-hour continuous exposure group. It was therefore considered to have no toxicological significance. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Tabulated results are detailed in the attached pdf document, Appendix I
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
The test material did not induce a toxicologically significant increase in the frequency of cells with chromosome aberrations in either the absence or presence of a liver enzyme metabolising system. The test material was therefore considered to be non-clastogenic to human lymphocytes in vitro.
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