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EC number: 832-365-4 | CAS number: 1184581-58-5
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 4-(3,5-dichlorobenzamido)-3-hydroxybenzoic acid
- EC Number:
- 832-365-4
- Cas Number:
- 1184581-58-5
- Molecular formula:
- C14H9Cl2NO4
- IUPAC Name:
- 4-(3,5-dichlorobenzamido)-3-hydroxybenzoic acid
- Test material form:
- solid: particulate/powder
- Details on test material:
- Batch E010014831, re-test date: 30 June 2015
Constituent 1
- Specific details on test material used for the study:
- Description White to off white powder
Batch E010014831
Purity/Composition 99.5%
Test substance storage At room temperature in the dark
Stable under storage conditions until 30 June 2015 (Retest date)
Purity/composition correction factor Not required
Stability at higher temperatures Not indicated
Stability in vehicle Dimethyl sulfoxide: Unknown
Solubility in vehicle Dimethyl sulfoxide: Not indicated
Method
- Target gene:
- S. typhimurium- histidine
E. coli - Tryptophan
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Additional strain / cell type characteristics:
- other: rfa, gaol, chl, bio, uvrB
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver microsomal enzymes (S9 homogenate); male Sprague Dawley; Aroclor
- Test concentrations with justification for top dose:
- Dose range finding test: 3, 10, 33, 100, 333, 1000, 3330 and 5000 µg/plate
Main test: 3, 10, 33, 100, 333, 1000, 3330 µg/plate- Due to precipitate of the test substance on the
plates, the highest concentration of PF-06410251 used in the subsequent mutation assay was 3330
µg/plate. - Vehicle / solvent:
- DMSO
Controls
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 2-nitrofluorene
- sodium azide
- methylmethanesulfonate
- other: ICR-191: TA 1537 2.5µg/plate; 2 aminoanthracene- all strains +S9 1-15µg/plate
- Details on test system and experimental conditions:
- Test system Salmonella typhimurium bacteria and Escherichia coli bacteria
Rationale Recommended test system in international guidelines (e.g. OECD, EC).
Source Trinova Biochem GmbH, Germany (Master culture from Dr. Bruce N. Ames)
(TA1535: 2006, TA1537: 2009, TA98: 2006, TA100: 2006) and (Master culture
from The National Collections of Industrial and Marine Bacteria, Aberdeen, UK)
(WP2uvrA, 2008)
The characteristics of the different Salmonella typhimurium strains were as follows:
Strain Histidine mutation Mutation type
TA1537 his C3076 Frameshift
TA98 hisD3052/R-factor* Frameshift
TA1535 his G46 Base-pair substitutions
TA100 his G46/R-factor* Base-pair substitutions
*: R-factor = plasmid pKM101 (increases error-prone DNA repair)
Each tester strain contained the following additional mutations:
rfa : deep rough (defective lipopolysaccharide cellcoat)
gal : mutation in the galactose metabolism
chl : mutation in nitrate reductase
bio : defective biotin synthesis
uvrB : loss of the excision repair system (deletion of the ultraviolet-repair B gene)
The Salmonella typhimurium strains are regularly checked to confirm their histidine-requirement,
crystal violet sensitivity, ampicillin resistance (TA98 and TA100), UV-sensitivity and the number of
spontaneous revertants.
The Escherichia coli WP2
uvrA strain detects base-pair substitutions. The strain lacks an excision repair
system and is sensitive to agents such as UV. The sensitivity of the strain to a wide variety of
mutagens has been enhanced by permeabilization of the strain using Tris-EDTA treatment (Ref.1).
The strain is regularly checked to confirm the tryptophan-requirement, UV-sensitivity and the number
of spontaneous revertants.
Stock cultures of the five strains were stored in liquid nitrogen (-196°C). - Evaluation criteria:
- A Salmonella typhimurium reverse mutation assay and/or Escherichia coli reverse mutation assay is
considered acceptable if it meets the following criteria:
a) The negative control data (number of spontaneous revertants per plate) should be within the
laboratory historical range for each tester strain.
b) The positive control chemicals should produce responses in all tester strains, which are within the
laboratory historical range documented for each positive control substance. Furthermore, the mean
plate count should be at least three times the concurrent vehicle control group mean.
c) The selected dose range should include a clearly toxic concentration or should exhibit limited
solubility as demonstrated by the preliminary toxicity range-finding test or should extend to
5 mg/plate. - Statistics:
- No formal hypothesis testing was done.
A test substance is considered negative (not mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 is not greater than two (2) times the
concurrent control, and the total number of revertants in tester strains TA1535, TA1537, TA98 or
WP2uvrA is not greater than three (3) times the concurrent vehicle control.
b) The negative response should be reproducible in at least one independently repeated experiment.
A test substance is considered positive (mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 is greater than two (2) times the concurrent
control, or the total number of revertants in tester strains TA1535, TA1537, TA98 or WP2uvrA is
greater than three (3) times the concurrent vehicle control.
b) In case a repeat experiment is performed when a positive response is observed in one of the tester
strains, the positive response should be reproducible in at least one independently repeated
experiment.
The preceding criteria were not absolute and other modifying factors might enter into the final
evaluation decision
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
Dose range finding test/first mutation experiment
PF-06410251 was tested in the tester strains TA100 and WP2uvrA with concentrations of 3, 10, 33,
100, 333, 1000, 3330 and 5000 µg/plate in the absence and presence of S9-mix. Based on the results
of the dose range finding test, the following dose range was selected for the mutation assay with the
tester strains, TA1535, TA1537 and TA98 in the absence and presence of S9-mix: 33, 100, 333, 1000
and 3330 µg/plate. The results are shown in Table 1 and Table 2.
Precipitate
Precipitation of PF-06410251 on the plates was observed at the start and at the end of the incubation
period at concentrations of 3330 µg/plate and upwards.
Toxicity
To determine the toxicity of PF-06410251, the reduction of the bacterial background lawn, the increase
in the size of the microcolonies and the reduction of the revertant colonies were examined.
The bacterial background lawn was not reduced at any of the concentrations tested and no biologically
relevant decrease in the number of revertants was observed up to the dose level of
3330 µg/plate. Since PF-06410251 precipitated heavily on the plates at the test substance
concentration of 5000 µg/plate the number of revertant colonies of this dose level could not be
determined.
Mutagenicity
No increase in the number of revertants was observed upon treatment with PF-06410251 under all
conditions tested.
Experiment 2
To obtain more information about the possible mutagenicity of PF-06410251, a second mutation
experiment was performed in the absence of S9-mix and in the presence of 10% (v/v) S9-mix. Based
on the results of the first mutation assay, PF-06410251 was tested up to the dose level of
3330 µg/plate in strains TA1535, TA1537, TA98, TA100 and WP2uvrA.
Precipitate
Precipitation of PF-06410251 on the plates was observed at the start and at the end of the incubation
period at the concentration of 3330 µg/plate.
Toxicity
In the second mutation assay, there was no reduction of the bacterial background lawn and no
biologically relevant decrease in the number of revertants at any of the concentrations tested in all
tester strains in the absence and presence of S9-mix.
Mutagenicity
In the second mutation assay, no increase in the number of revertants was observed upon treatment
with PF-06410251 under all conditions tested.
Applicant's summary and conclusion
- Conclusions:
- All bacterial strains showed negative responses over the entire dose range, i.e. no significant doserelated
increase in the number of revertants in two independently repeated experiments.
The negative and strain-specific positive control values were within the laboratory historical control
data ranges indicating that the test conditions were adequate and that the metabolic activation system
functioned properly.
Based on the results of this study it is concluded that PF-06410251 is not mutagenic in the Salmonella
typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay. - Executive summary:
Evaluation of the mutagenic activity of PF-06410251 in the Salmonella typhimurium reverse mutation
assay and the Escherichia coli reverse mutation assay (with independent repeat).
PF-06410251 was tested in the Salmonella typhimurium reverse mutation assay with four histidinerequiring
strains of Salmonella typhimurium (TA1535, TA1537, TA98 and TA100) and in the Escherichia
coli reverse mutation assay with a tryptophan-requiring strain of Escherichia coli (WP2uvrA).
The test was performed in two independent experiments in the presence and absence of
S9-mix (rat liver S9-mix induced by Aroclor).
The study procedures described in this report were based on the most recent OECD and EC
guidelines.
Batch E010014831 of PF-06410251 was a white to off white powder with a purity of 99.5%. The test
substance was dissolved in dimethyl sulfoxide.
In the dose range finding test, PF-06410251 was tested up to concentrations of 5000 µg/plate in the
absence and presence of S9-mix in the strains TA100 and WP2uvrA. PF-06410251 precipitated on the
plates at dose levels of 3330 and 5000 µg/plate. The bacterial background lawn was not reduced at
any of the concentrations tested and no biologically relevant decrease in the number of revertants was
observed up to the dose level of 3330 µg/plate. Since PF-06410251 precipitated heavily on the plates
at the test substance concentration of 5000 µg/plate, the number of revertant colonies of this dose
level could not be determined. Results of this dose range finding test were reported as part of the first
mutation assay.
Based on the results of the dose range finding test, PF-06410251 was tested in the first mutation
assay at a concentration range of 33 to 3330 µg/plate in the absence and presence of 5% (v/v) S9-mix
in tester strains TA1535, TA1537 and TA98. In an independent repeat of the assay with additional
parameters, PF-06410251 was tested at the same concentration range as the first assay in the
absence and presence of 10% (v/v) S9-mix in tester strains TA1535, TA1537, TA98, TA100 and
WP2uvrA. PF-06410251 precipitated on the plates at the top dose of 3330 µg/plate. The bacterial
background lawn was not reduced at any of the concentrations tested and no biologically relevant
decrease in the number of revertants was observed.
PF-06410251 did not induce a significant dose-related increase in the number of revertant (His+)
colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of
revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic
activation. These results were confirmed in an independently repeated experiment.
In this study, the negative and strain-specific positive control values were within the laboratory
historical control data ranges indicating that the test conditions were adequate and that the metabolic
activation system functioned properly.
Based on the results of this study it is concluded that PF-06410251 is not mutagenic in the Salmonella
typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
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