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EC number: 200-860-9 | CAS number: 75-31-0
- 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
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- Endpoint summary
- Stability
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- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Isopropylamine did not show mutagenic activity either in the bacterial reverse mutation assay (Ames test) or in mammalian cell culture assays for chromosome aberration and gene mutation (HPRT).
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study, part of NTP/USA, but incomplete test strain set according to OECD guideline 471
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- preincubation assay, two different sources of a microsomal metabolic system; 4 instead of 5 tester strains.
- Principles of method if other than guideline:
- Ames-Test modified acc. to Haworth et al. (1983): Environ. Mutagen. 5, Suppl. 1, 3-142
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Metabolic activation systems were derived from Arochlor-induced livers of male SD rats and male Syrian hamsters.
- Test concentrations with justification for top dose:
- 0.010, 0.033, 0.100, 0.333, 1.0, 3.333 mg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Test substance well soluble in water - Untreated negative controls:
- no
- Remarks:
- corresponds to vehicle control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: -S9: Sodium azide (TA1535, TA100); 9-aminoacridine (TA1537); 4-nitro-o-phenylenediamine (TA98) // +S9: 2-aminoanthracene (all strains).
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation, agar plate
DURATION
- Preincubation period: 20 min
- Exposure duration: 2 days at 37 °C
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- relative total growth (background lawn)
- Evaluation criteria:
- Mutagenic (+) or weakly mutagenic (+w) if a reproducible, dose-related increase in revertants over the corresponding solvent controls in replicate trials was seen.
Questionable (?) if a reproducible increase in revertants did not meet the criteria of either "+" or "+w", or if single doses produced an increase in repeat trials. - Key result
- 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:
- cytotoxicity
- Remarks:
- >= 3.333 mg/plate (see Report, Appendix 2, p. 79/80)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- --
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under the conditions of this study there was no mutagenicity in bacteria with and without metabolic activation
- Executive summary:
The mutagenic activity of the test substance (purity > 99%) was examined in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 in concentrations of 0, 10, 33, 100, 333, 1000, 3333 and 10000 µg/plate, without or with metabolic activation by Aroclor 1254-induced rat and hamster S9 liver extracts.
No cytotoxicty was observed up to the highest concentration.The test item did not produce a mutagenic response in any of the strains tested with or without metabolic activation.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- as of 1997
- Principles of method if other than guideline:
- HPRT assay for the detection of mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (6-thioguanine [6TG] resistance) in mouse lymphoma cells using a fluctuation protocol according to Cole et al. 1983.
Reference:
Cole J, Arlett C F, Green M H L, Lowe J and Muriel W 1983: A comparison of the agar cloning and microtitration techniques for assaying cell survival and mutation frequency in L5178Y mouse lymphoma cells. Mutation Research, 111, 317-386 - GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Induction of a forward mutation in the X-linked hprt locus: Resistance to the toxic analogue 6-thioguanine (6TG) results from lack of hypoxanthine-guanine phosphoribosyl transferase (HPRT) activity. Thus, the hprt-negative mutants are unable to use 6TG and survive in its presence.
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI media (containing antibiotics and varying concentrations of horse serum, heat-inactivated, from 0 - 20 %)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes,
- Other procedures: purge of TK-negative mutants - Additional strain / cell type characteristics:
- other: TK proficient (TK+)
- Metabolic activation:
- with and without
- Metabolic activation system:
- post-mitochondrial fraction from livers of male SD rats previously induced with Arochlor-1254
- Test concentrations with justification for top dose:
- Experiment 1: 0, 80, 120, 210, 240, and 270 µg/mL (evaluated)
Experiment 2: 0, 100, 150, 175, 200, 250, 300, and 400 µg/mL (evaluated) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: sufficient water solubility of the test substance - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water as vehicle
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitroquinoline-N-oxide (-S9); benzo(a)pyrene (+S9)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium, incubation in centrifuge tubes, culture flasks, and wells of microtiter plates,
depending on the operation step
DURATION
- Preincubation period: no data, pre-culture in RPMI 10 after thawing up to an appropriate cell density
- Exposure duration: 3 h
- Incubation temperature: 37 +- 1 °C
- Expression time (cells in growth medium): 7 d
- Selection time (if incubation with a selection agent): 12 d
SELECTION AGENT (mutation assays): 6-thioguanine (6-TG)
NUMBER OF REPLICATIONS: 2
NUMBER OF CELLS EVALUATED: Selection of 6-TG resistance: 4 microtiter plates of 90 wells at 2 x10^4 cells per well each
(= 384 x2 x10^4 cells per test concentration)
DETERMINATION OF CYTOTOXICITY
- Method: Relative survival in the presence and absence of test substance (by visual counting of viable clones in microtiter plates)
DETERMINATION of VIABILITY (after expression period)
- Method: visual counting of viable clones in microtiter plates
DETERMINATION of 6-TG RESISTANCE (after expression period)
- Method: visual inspection of microtiter plates for the number wells containing clones. - Evaluation criteria:
- ACCEPTANCE CRITERIA
The assay was considered valid if the following criteria were met:
1. the mutant frequencies in the negative (vehicle) control cultures fell within the normal range (not more than three times the historical mean value)
2. at least one concentration of each of the positive control chemicals induced a clear increase in mutant frequency (the difference between the positive and negative control mutant frequencies was greater than half the historical mean value).
EV ALUATION CRITERIA
For valid data, the test article was considered to induce forward mutation at the hprt locus in mouse lymphoma L5178Y cells if:
1. the mutant frequency at one or more concentrations was significantly greater than that of the negative control (p < 0.05)
2. there was a significant concentrationrelationship as indicated by the linear trend analysis (p < 0.05)
3. the effects described above were reproducible.
Results that only partially satisfied the assessment criteria described above were considered on a case-by-case basis. - Statistics:
- Statistical significance of mutant frequencies was carried out according to the UKEMS guidelines. Thus the control log mutant frequency (LMF) was compared with the LMF from each treatment concentration, and secondly the data were checked for a linear trend in mutant frequency with test article treatment. These tests require the calculation of the heterogeneity factor to obtain a modified estimate of variance.
Reference:
Robinson et al. 1990: Statistical evaluation of bacterial/mammalian fluctuation tests. In Statistical Evaluation of Mutagenicity Test Data (Ed D J Kirkland), Cambridge University Press, pp 102 – 140. - Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- dose-related: The highest concentrations to provide >10 % RS were 148 µg/mL +S9 and 296 µg/mL -S9.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: marked increases of >= 1 pH unit at >= 240 µg/mL
- Effects of osmolality: no
- Evaporation from medium: no
- Precipitation: only at the highest concentration (which turned out to be too toxic)
RANGE-FINDING/SCREENING STUDIES: for cytotoxicity testing up to solublity limit of 500 µg/mL
COMPARISON WITH HISTORICAL CONTROL DATA: Acceptance criterion, Control/Historical ratio > 0.5, fulfilled for positive controls
(See Appendices) - Remarks on result:
- other: strain/cell type: mouse lymphoma L5178Y cells
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The test substance did not induce mutations at the HPRT locus of L5178Y mouse lymphoma cells under test conditions employed in this study. This included treatments up to highly toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system.
- Executive summary:
Isopropylamine (MIPA) was assayed for mutation at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (6-thioguanine [6TG] resistance) in mouse lymphoma cells using a fluctuation protocol. The study consisted of a cytotoxicity Range-Finder Experiment followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post-mitochondrial fraction (S-9). Test article formulations were prepared in purified water.
In the cytotoxicity Range-Finder Experiment, six concentrations were tested in the absence and presence of S-9, ranging from 18.5 to 592 μg/mL (equivalent to 10 mM at the highest concentration tested). The highest concentrations to provide >10% RS were 148 μg/mL in the absence of S-9 and 296 μg/mL in the presence of S-9, which gave 33% and 26% relative survival (RS), respectively.
In Experiment 1, ten concentrations, ranging from 40 to 350 μg/mL in the absence of S-9 and from 40 to 400 μg/mL in the presence of S-9 were tested. Seven days after treatment the highest concentrations analysed for viability and 6TG resistance were 270 μg/mL in the absence of S-9 and 350 μg/mL in the presence of S-9, which gave 19% and 17% RS, respectively.
In Experiment 2, ten concentrations, ranging from 50 to 400 μg/mL in the absence of S-9 and from 50 to 500 μg/mL in the presence of S-9, were tested. Seven days after treatment the highest concentrations analysed for viability and 6TG resistance were 400 μg/mL in the absence of S-9 and 375 μg/mL in the presence of S-9, which gave 3% and 20% RS, respectively.
Negative (vehicle) and positive control treatments were included in each Mutation Experiment in the absence and presence of S-9. Mutant frequencies in negative control cultures fell within normal ranges and clear increases in mutation were induced by the positive control chemicals 4-nitroquinoline 1-oxide (without S-9) and benzo(a)pyrene (with S-9). Therefore the study was accepted as valid.
In Experiments 1 and 2, no statistically significant increases in mutant frequency were observed following treatment with Isopropylamine (MIPA) at any concentration tested in the absence and presence of S-9 and there were no significant linear trends. Although a concentration giving <10% RS was analysed in the presence of S-9 in Experiment 2 there was no evidence of mutagenic activity at any concentration,
therefore this did not affect data interpretation.
It is concluded that Isopropylamine (MIPA) did not induce mutation at the HPRT locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to highly toxic concentration in two independent experiments in the absence and presence of a rat liver metabolic activation system (S-9).
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Remarks:
- However, in the presence of S9-mix, selection of the dose levels was based on pH and not on the mitotic index, since the use of non-physiological pH was not recommended.
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- lymphocytes: human
- Details on mammalian cell type (if applicable):
- - Donators: two healthy humans with no recent X-ray exposure and believed to be free of viral infection
- Time: on day of of culture
- Culture: whole blood in sterile tubes containing heparin - Metabolic activation:
- with and without
- Metabolic activation system:
- liver microsomal fraction (S9) of male SD rats induced with Arochlor 1254
- Test concentrations with justification for top dose:
- -S9 mix: 0, 10, 30, 100, 300, 1000 and 5000 µg/mL
+S9 mix: 250, 500, and 1000 µg/mL
Doses used for evaluation:
-S9-mix: 30, 100, and 300 µg/mL. 300 µg/mL produced moderate cytotoxicity
+S9-mix: 250, 500, and 1000 µg/mL - Vehicle / solvent:
- distilled water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water control
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: mitomycin C (- S9); cyclophosphamide (+S9)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 24 and 48 h (-S9); 2 h (+S9)
- Fixation time (start of exposure up to fixation or harvest of cells): 24 and 48 h(+/-S9)
SPINDLE INHIBITOR (cytogenetic assays): Colcemid, applied 2 h before harvest
NUMBER OF REPLICATIONS: 2 per dose and interval
NUMBER OF CELLS EVALUATED: 200 metaphases per dose and interval
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index, evaluated on 1000 cells each
OTHER EXAMINATIONS:
- Determination of polyploidy: yes
- Determination of endoreplication: yes
- Other: gaps, chromatid / chromosomal breaks and exchanges, multiple aberrations and pulverisation
- Evaluation criteria:
- Validity:
- Aberrant cell frequencies (excluding gaps) in the controls fell within the range of historical data;
- the positive controls induced statistically significant increases in the aberrent cell frequencies that fall within the historical contrl ranges.
Evaluation criteria:
- a statistically significant increase in the aberrant cell frequency for at least one of the doses, for any harvest time.
- Statistics:
- X2 test (significance level of P = 0.05) to compare mean aberration frequencies with the controls.
- Key result
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at >=300µg/mL (-S9), no cytotoxicity (+S9)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: cytotoxicity
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- At 300 and 1000 µg/ml, the pH values were 8 and 10, respectively.
- 5000 µg/ml were hemolytic to the cells.
MITOTIC INDEX:
- With metabolic activation (Report, Table 3 and 4):
1000 µg/ml (2 treatment / 24 h harvest): 87 % of the control
1000 µg/ml (2 treatment / 48 h harvest): 93 % of the control
- Without metabolic activation (Report, Table 1 and 2):
300 µg/ml (24 h treatment/24 h harvest): 66 % of the control
1000 µg/ml (24 h treatment/24 h harvest): 0 % of the control
300 µg/ml (48 treatment/48 h harvest): 76 % of the control
1000 µg/ml (48 h treatment/48 h harvest): 45 % of the control - Remarks on result:
- other: strain/cell type: human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under the conditions of this study the test substance did not produce chromosomal aberrations in human lymphocytes with and without metabolic activation
- Executive summary:
The objective of this study was to evaluate the potential of the test substance to induce chromosome breakage in cultured human lymphocytes in a GLP-compliant study according to OECD guideline 473. The testing was performed with concentrations of 0, 10, 30, 100, 300, 1000 or 5000 µg/mL for 24 or 48 h (without metabolic activation with rat S9 liver fraction). With metabolic activation the exposure concentrations were 0, 250, 500 and 1000 µg/mL and the exposure time 2 h. These cells were further incubated in fresh medium to the harvest time of 24 or 48 h.
The test substance did not induce any significant increase in the frequency of aberrant cells with or without metabolic activation. The percentage of aberrant cells of controls was within the range of historical data. The positive control substances induced a significant increase in aberrant cells.
Therefore under the conditions of this study the test substance was not considered to exert clastogenic activity.
Referenceopen allclose all
Summary of mutation data [mean of two replicate cultures]:
Experiment 1 (3 hour treatment in the absence and presence of S-9)
[for individual replicates, see Appendix 2, Table 10 (-S9), and Appendix 3, Table 18 (+S9)]
Treatment (µg/mL) |
-S-9 |
Treatment (µg/mL) |
+S-9 |
||||||||
% RS |
MF§ |
% RS |
MF§ |
||||||||
0 |
100 |
1.28 |
0 |
100! |
1.26 |
||||||
80 |
97 |
0.23 |
NS |
40 |
85 |
1.79 |
NS |
||||
120 |
81 |
1.22 |
NS |
200 |
66 |
2.11 |
NS |
||||
210 |
36 |
2.66 |
NS |
240 |
58 |
0.51 |
NS |
||||
240 |
30 |
1.62 |
NS |
280 |
45 |
1.94 |
NS |
||||
270 |
19 |
0.78 |
NS |
300 |
33 |
2.20 |
NS |
||||
350 |
17 |
0.39 |
NS |
||||||||
Linear trend |
NS |
Linear trend |
NS |
||||||||
NQO |
B[a]P |
||||||||||
0.1 |
44 |
19.72 |
2 |
54 |
10.78 |
||||||
0.15 |
34 |
40.90 |
3 |
20 |
48.09 |
||||||
Experiment 2 (3 hour treatment in the absence and presence of S-9)
[for individual replicates, see Appendix 4, Table 26 (-S9), and Appendix 5, Table 34 (+S9)]
Treatment (µg/mL) |
-S-9 |
Treatment (µg/mL) |
+S-9 |
||||||||
% RS |
MF§ |
% RS |
MF§ |
||||||||
0 |
100 |
5.14 |
0 |
100 |
6.41 |
||||||
100 |
98 |
4.46 |
NS |
200 |
90 |
7.21 |
NS |
||||
150 |
82 |
4.28 |
NS |
250 |
93 |
3.43 |
NS |
||||
175 |
70 |
4.92 |
NS |
300 |
60 |
4.95 |
NS |
||||
200 |
56 |
4.65 |
NS |
325 |
53 |
5.67 |
NS |
||||
250 |
36 |
2.97 |
NS |
350 |
32 |
4.64 |
NS |
||||
300 |
28 |
5.45 |
NS |
375 |
20 |
5.70 |
NS |
||||
400 |
3 |
6.88 |
NS |
||||||||
Linear trend |
NS |
Linear trend |
NS |
||||||||
NQO |
B[a]P |
||||||||||
0.1 |
59 |
54.25 |
2 |
66 |
80.64 |
||||||
0.15 |
58 |
66.29 |
3 |
39 |
104.52 |
||||||
§ = 6TG resistant mutants/106viable cells 7 days after treatment
% RS = Percent relative survival adjusted by post treatment cell counts
NS = not significant
! = Based on one replicate only
The aberrant cell frequencies in the negative controls were within the range of the historical data (0.4 +/-0.5 %), gaps excluded.
The aberrant cell frequencies in the positive controls were significantly higher than that of the negative controls (P 0.001).
Overview of aberrant cell frequency (from Report, Table 1 and 2):
Number of aberrations |
% aberrant cells |
|||||||
Doses [µg/mL] |
+ gaps |
- gaps |
+ gaps |
- gaps |
||||
Without metabolic activation: 24 / 24 h or 48 / 48 h exposure / harvest time |
||||||||
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
|
0 |
3 |
3 |
1 |
2 |
1.5 |
1.5 |
1.5 |
1.0 |
30 |
4 |
6 |
2 |
2 |
2.0 |
3.0 |
1.0 |
1.0 |
100 |
4 |
1 |
0 |
1 |
2.0 |
0.5 |
0.0 |
0.5 |
300 |
1 |
3 |
1 |
2 |
0.5 |
1.5 |
0.5 |
1.0 |
MMC [0.2] |
42 |
- |
36 |
- |
19 |
- |
16 |
- |
MMC = mitomycin
Overview of aberrant cell frequency (from Report, Table 3 and 4):
Number of aberrations |
% aberrant cells |
|||||||
Doses [µg/mL] |
+ gaps |
- gaps |
+ gaps |
- gaps |
||||
With metabolic activation: 2 / 24 h or 2 / 48 h exposure / harvest time |
||||||||
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
24 h |
48 h |
|
0 |
2 |
2 |
1 |
2 |
1.0 |
1.0 |
0.5 |
1.0 |
250 |
5 |
2 |
3 |
1 |
2.5 |
1.0 |
1.5 |
0.5 |
500 |
4 |
5 |
2 |
1 |
2.0 |
2.5 |
1.0 |
0.5 |
1000 |
1 |
2 |
0 |
1 |
0.5 |
1.0 |
0.0 |
0.5 |
CPA [50] |
60 |
- |
50 |
- |
21.5 |
- |
19.5 |
- |
CPA = cyclophosphamide
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
In the absence of information on a species specific mode of action the information obtained in the in vitro studies are regarded as relevant for humans.
Additional information
Additional information from genetic toxicity in vitro:
In a study conducted in a manner equivalent or similar to OECD
Guideline 471 (Bacterial Reverse Mutation Assay) bacterial strainsS.
typhimurium TA 1535, TA 1537, TA 98 and TA 100 were exposed to 0.010,
0.033, 0.100, 0.333, 1.0 or 3.333 mg/plate isopropylamine in the
presence and absence of metabolic activation systems derived from
Arochlor-induced livers of male SD rats and male Syrian hamsters (Zeiger
et al., 1987). Cytotoxicity as reported at >= 3.333 mg/plate. Positive
and negative controls were included and results indicated the test was
sensitive and valid. Isopropylamine did not induce revertants in any
bacterial strains tested both with and without metabolic activation.
Even though the set of test strains did not include the strain TA102 or E. Coli WP2 uvrA which can detect mutations due to formation of reactive oxygen species (ROS) or DNA cross-links, this is not regarded as a major drawback of the study and for the overall evaluation of possible mutagenicity of the registration substance. It can reasonably be assumed that in case isopropylamine would induce ROS or DNA cross-links effects would have been detected in the other available mutagenicity tests. However, as neither gene mutations in mammalian cells in vitro (HPRT locus in mouse lymphoma test) nor chromosomal aberrations in vitro were induced in these reliable genotoxicity tests, it can reasonably be assumed that isopropylamine would not have been mutagenic in the lacking tester strain in the Ames test. Therefore, it is concluded, that on basis of this overall weight of evidence isopropylamine is not mutagenic and has not to be classsified for mutagenicity.
This assessment is supported by negative findings in a OECD 471 -compliant Ames test for the structurally related n-propylamine (see corresponding IUCLID dossier) where negative results were also obtained in E.Coli WP2 uvrA.
In an OECD Guideline 473 (In vitro Mammalian Chromosome Aberration Test) human lymphocytes were exposed to isopropylamine in the absence of metabolic activation for 24 and 48 hours at 30, 100, and 300 μg/mL and in the presence of metabolic activation for 2 hours at 250, 500, and 1000 μg/mL (Molinier, 1994). Cytotoxicity was reported in the absence of metabolic activation at >=300μg/mL; in the absence of metabolic activation there was no reported cytotoxicity. Positive and negative controls were included and results indicated the test was sensitive and valid. Isopropylamine did not induce chromosome aberrations in this study.
In an OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test) mouse lymphoma L5178Y cells were exposed to isopropylamine with and without metabolic activation as follows: Experiment 1: 0, 80, 120, 210, 240 or 270 μg/mL (evaluated); Experiment 2: 0, 100, 150, 175, 200, 250, 300 or 400 μg/mL (evaluated) (Stone, 2010). The highest concentrations to provide >10 % RS were 148 μg/mL with activation and 296 μg/mL without activation. Positive controls were included and results indicated the test was sensitive and valid. Isopropylamine did not induce mutation at the HPRT locus of L5178Y mouse lymphoma cells under test conditions employed in this study. This included treatments up to highly toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system.
Justification for classification or non-classification
Based on the negative findings in several in vitro studies it is concluded that isopropylamine has not to be classified as genotoxic according to Regulation (EC) No 1272/2008.
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