Isopropylamine

Endpoint summary

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

Reference

Reference 1

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.

Reference 2

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 concentration﷓relationship 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'.

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

         

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).

Reference 3

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'.

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

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.

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.