3-isopropoxypropylamine

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

Study period:

end 1998-02-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1A: GLP, OECD n°471 guideline, N° 92/69/E.E.C. Annex V, B14

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-isopropoxypropylamine

EC Number:

220-816-2

EC Name:

3-isopropoxypropylamine

Cas Number:

2906-12-9

Molecular formula:

C6H15NO

IUPAC Name:

3-(propan-2-yloxy)propan-1-amine

Details on test material:

- Name of test material (as cited in study report): 3-Isopropxypropylamine
- Physical state: liquid
- Analytical purity: 99.78%
- Purity test date: 1997-08-07
- Lot/batch No.: 9708P0073
- Expiration date of the lot/batch: December 1998
- Stability under test conditions: no data
- Storage condition of test material: in dark and at room temperature
- Other: origin: Unsine de Maurienne, La Chambre

Method

Target gene:

Histidine operon

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Metabolic activation system:

liver microsomal fraction induced with Aroclor 1254

Test concentrations with justification for top dose:

156.25, 312.5, 625, 1250, and 2500µg/plate for TA 100, TA 1535 in the first experiment and TA 98 in the second experiment
312.5,, 625, 1250, 2500 and 5000µg/plate for TA 1537, TA 102, TA98 in the first experiment and TA 1535 in the second experiment.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

-S9: TA1535 TA100 (sodium azide 1µg/plate); -S9: TA1537 (9-aminoacridine 50µg/plate); -S9: TA98 (2-nitrofluorene 0.5µg/plate); -S9: TA102 (mitomycin C 0.5µg/plate); +S9: TA1535, TA1537, TA98, TA100 (2-anthramine 2µg/plate) and TA102 (10µg/plate)

Details on test system and experimental conditions:

METHOD OF APPLICATION:
in agar (plate incorporation): 1st experiment and 2nd expeirment for TA 1535 only
preincubation: 2nd experiment for all strains except TA 1535
Preincubation period: 60min at 37°C

Revertants scoring after 48 to 72 hours of incubation at 37°C

Evaluation criteria:

A reproductible 2-fold increase in the number of revertants compared with the vehicle controls, in any strains at any dose level and/or evidence of a dose-relationship was considered as a positive result

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1537, TA 98, TA 100, TA 102

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

TA 1535

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at highest doses (2500µg/plate and above)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Results for the positive strain TA1535 with S9mix (direct incorporation method)

SD=standard deviation

Strain	Doses (µg/plate)	revertants per plate			mean	SD	ratio
TA 1535	0	5	17	16	13	7
	625	10	17	17	15	4	1,16
	1250	15	15	14	15	1	1,16
	2500	58	17	26	334	22	2,66
	3500	67	80	87	78	10	6,16
	5000	57	64	65	62	4	4,89
	2AM	258	251	249	253	5	19,95

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation in 1 strain (TA 1535).
negative with metabolic activation in 4 strains (TA 1537, TA 98, TA 100 and TA 102)
negative without metabolic activation in all strains

3-isopropoxypropylamine showed mutagenic activity in the Ames test on Salmonella typhimurium TA 1535 strain with metabolic activation.

Executive summary:

The genotoxic activity of 3-isopropoxypropylamine was evaluated in the Ames test onSalmonella typhimuriumaccording to the OECD 471 guideline (Haddouk, 1998). Doses from 156.25 to 5000µg/plate were tested on five strains (TA 98, TA 100, TA 1535, TA 1537 and TA 102) in presence or absence of metabolic activation. Two methods were used: direct plate incorporation (1st experiment and 2nd experiment for TA 1535 only) and preincubation 60 min at 37°C (2^ndexperiment for all strains except TA 1535) and the number of revertants colonies is evaluated 48 to 72 hours later. The number of revertants of the vehicle and positive controls was as specified in the acceptance criteria. Without metabolic activation, the test substance did not induce any significant increase in the number of revertants, in any of the 5 strains. With metabolic activation, an increase of the number of revertant colonies was observed at the dose level of 2500 µg/plate for the TA1535 strain (2.66-6.16 fold higher than control values). In conclusion, 3-isopropoxypropylamine showed mutagenic activity in the Ames test onSalmonella typhimuriumTA 1535 strain in the absence metabolic activation.