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EC number: 200-441-0 | CAS number: 59-67-6
- 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 gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Report date:
- 1984
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inveresk Research International
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Nicotinic acid
- EC Number:
- 200-441-0
- EC Name:
- Nicotinic acid
- Cas Number:
- 59-67-6
- Molecular formula:
- C6H5NO2
- IUPAC Name:
- nicotinic acid
- Test material form:
- solid: crystalline
- Details on test material:
- - Name of test material: Nicotinic acid
Constituent 1
Method
- Target gene:
- Five strains of Salmonella typhimurium were used:
S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100
They were obtained in 1976 from Professor B.N. Ames, Department of Biochemistry. University of California, Berkeley, CA., U.S.A., and stored in liquid nitrogen since that time until used.
All these strains contain mutations in the histidine operon, thereby imposing a requirement for histidine in the growth medium. Three mutations in the histidine operon are involved:
his G 46 in TA 1535 and TA 100
his C 3076 in TA 1537
his D 3052 in TA 1538 and TA 98
All 5 strains contain the deep rough (rfa) mutation, which deletes the polysaccharide side chain of the lipopolysaccharide coat of the bacterial cell surface. This deletion increases cell permeability to more hydro phobic substances and, furthermore, greatly decreases the pathogenicity of these organisms.
The second deletion through uvrB, renders the organisms incapable of DNA excision repair and thus more susceptible to mutagenicity. These 2 deletions include the nitrate reductase (chl) and biotin (bio) genes also. Differences between TA 1535 and TA 1538, on the one hand, and the corresponding TA 100 and TA 98 strains on the other hand, are due to a plasmid the latter pair contains. A plasmid, R-Utrecht, was originally shown to increase the sensitivity of the his G 46 mutation in S. typhimurium to methyl methanesulphonate and trimethyl phosphate. The particular R-factor in TA 100 and TA 98 carried resistance to ampicillin. It is not yet clear why the presence of this particular R-factor should increase the sensitivity of strains TA 1535 and TA 1538 to the mutagenicity of certain chemicals. The involvement of an error-prone repair mechanism has been postulated.
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Vogel-Bonner Medium E agar plates with 2% glucose obtained from Gibco Europe limited, Paisley, Scotland.
- Properly maintained: yes - Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- S. typhimurium TA 1538
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Vogel-Bonner Medium E agar plates with 2% glucose obtained from Gibco Europe limited, Paisley, Scotland.
- Properly maintained: yes - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254-induced rat liver preparation and co-factors (S9 mix)
- Test concentrations with justification for top dose:
- TOXICITY TEST
A toxicity test using strain TA 100 only was performed in the presence and absence of S9 mix to establish suitable dose levels for the mutation tests. One plate of each of the following concentrations of P0076D was used: 33 ug, 100 ug, 333 ug, 1000 ug, 3333 ug and 10000 ug per plate.
MUTATION ASSAY
Two independent mutation tests were conducted using 5 bacterial strains (TA 1535, TA 1537, TA 1538, TA 98 and TA 100). The dose levels used in both of these experiments and selected on the basis of the results of the toxicity test, were 33 ug, 100 ug, 333 ug, 1000 ug, 3333 ug and 10000 ug per plate. Triplicate plates were prepared for each bacterial strain and dose level in both the presence and absence of S9 mix. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Dimethylsulphoxide (DMSO) at 0.1 mL per plate, exception sodium azide dissolved in sterile, distilled water
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- without and with S9
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-Aminoanthracene
- Remarks:
- 1st test: all strains at 0.5 ug per plate with S9; 2nd test: TA 1537 at 1.0 ug per plate with S9
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- 1st and 2nd test: TA 1535 and TA 100 at 1 ug per plate
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- 1st and 2nd test: TA 1538 and TA 98 at 1 ug per plate
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- 1st and 2nd test: TA 1537 at 20 ug per plate
- Details on test system and experimental conditions:
- METHOD OF APPLICATION
- plate incorporation
DURATION
- Expression time (cells in growth medium): 48 hours
SELECTION AGENT (mutation assays)
- Histidine auxotrophs. Further, each strain was tested for its resistance to ampicillin (indicating the presence of pKM101) and sensitivity to crystal violet (indicating persistence of the rfa mutation).
NUMBER OF REPLICATIONS
- Two independent mutation tests were conducted. Triplicate plates were prepared for each bacterial strain and dose level in both the presence and absence of S9 mix.
DETERMINATION OF CYTOTOXICITY
- A toxicity test using strain TA 100 only was performed in the presence and absence of S9 mix to establish suitable dose levels for the mutation tests. - Evaluation criteria:
- A test was considered acceptable if for each strain:
i) the bacteria demonstrated their typical responses to crystal violet and ampicillin.
ii) at least 2 of the vehicle control plates were within the following ranges: TA 1535, 1-30; TA 1537, 1-20; TA 98, 10-60; TA 100, 60-200 and TA 1538, 10-35.
iii) on at least 2 of the positive control plates there were x 2 the mean vehicle control mutant numbers per plate, or for TA 100, x 1.5 the mean vehicle control mutant numbers per plate.
If the mean colony count on the vehicle control plate was less than 10 then a value of 10 was assumed for assessment purposes. In such cases a minimum count of 20 was required on at least 2 of the positive control plates.
iv) no toxicity or contamination was observed in at least 4 dose levels.
v) no more than one dose level was discarded before the highest significant mean colony number was achieved.
Where these criteria were met, a significant mutagenic response was recorded if there was:
i) for S. typhimurium strains TA 1535, TA 1537, TA 1538 and TA 98, at least a doubling of the mean concurrent vehicle control values at some concentration of the test substances and, for S. typhimurium strain TA 100, a 1.5-fold increase over the control value. If the mean colony count on the vehicle control plates was less than 10 then a value of 10 was assumed for assessment purposes. In such cases a minimum count of 20 was required before a significant mutagenic response was identified.
ii) a dose related response, although at high dose levels this relationship could be inverted because of, for example, (1) toxicity to the bacteria generally, (2) specific toxicity to the mutants and (3) inhibition of foreign compound metabolizing enzymes where mutagens require metabolic activation by the liver.
iii) a reproducible effect in independent tests.
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TOXICITY TEST
The sample was not toxic to the background lawn of bacteria either in the presence or absence of S9 mix when tested to a highest dose level of 10000 ug per plate.
MUTATION TESTS
Quality Control
All strains of S. typhimurium were sensitive to crystal violet, whereas only the plasmid-containing strains, TA 98 and TA 100, were resistant to ampicillin. These results are consistent with the known properties of these bacteria.
Vehicle Control Groups
The vehicle control values were within the normal ranges experienced in this laboratory and reported in the literature with these strains of S. typhimurium, except in one instance as detailed below (see Test Rejection).
Positive Control Groups
The results obtained with all positive controls in both tests were within the normal ranges expected for each bacterial strain and metabolic activation state.
Test Rejection
All tests were acceptable according to the study criteria except:
Test No 1: Strain TA 1538 without S9 Mix
Reason for Rejection: Inadequate vehicle control values
The results of the first test on the test item showed that the test substance did not induce significant increases in revertant numbers over vehicle control values in any strain of bacteria either in the presence or absence of S9 mix. No toxicity to the background lawn of bacteria was noted in this test.
The results of the second test confirmed that the test item did not give significant increases in revertant numbers in any of the strains used either in the presence or absence of S9 mix. No toxicity to the background lawn of bacteria was noted in this test.
Inadequate vehicle control values were obtained in the first test with strain TA 1538 in the absence of S9 mix, so a repeat test was performed with this strain. The results of this repeat test showed that the test item did not give significant increases in revertant numbers in strain TA 1538 in the absence of S9 mix. The test substance was not toxic to the bacteria in this repeat test. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
The test item was not mutagenic in any of the 5 strains of S. typhimurium used either in the presence or absence of S9 mix. No toxicity to the background lawn of bacteria was recorded in this study. - Executive summary:
A study according to EU Method B.13/14 and OECD Guideline 471 (Bacterial Reverse Mutation Assay) was carried out. The test item was assessed for mutagenic activity in Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 at concentrations ranging from 33 ug to 10000 ug per plate.
The tests were conducted on agar plates in the presence and absence of an Aroclor 1254-induced rat liver preparation and co-factors (S9 mix) required for mixed function oxidase activity. Concurrent positive controls demonstrated the sensitivity of the assay and the metabolizing activity of the S9 mix.
No toxicity to the bacteria was observed in any strain of bacteria. The test item was not mutagenic in any of the bacterial strains used in this study.
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