1,1'-iminodipropan-2-ol

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:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Salmonella Mutation Test (Ames) according to Haworth, S. et al.: Environ.Mutagen. 5, Suppl. 1, 3-142

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-iminodipropan-2-ol

EC Number:

203-820-9

EC Name:

1,1'-iminodipropan-2-ol

Cas Number:

110-97-4

Molecular formula:

C6H15NO2

IUPAC Name:

1,1'-iminodipropan-2-ol

Details on test material:

Purity 99%
Supplier: Strem Chemicals

Method

Target gene:

TA1537 hisC3076
TA1535 hisG46
TA100 hisG46
TA98 hisD3052

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S9 liver fraction from rats and hamsters treated with AROCLOR 1254

Test concentrations with justification for top dose:

100, 333, 1000, 3333, 10000 µg/plate

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide for TA1535 and TA100, 4-nitro-0-phenylenediamine for TA98, and 9-aminoacridine for TA1537 were used in assays without metabolic activation; 2-aminoanthracene was used in all assays as positive control with metabolic activation

Details on test system and experimental conditions:

All chemicals were assayed for mutagenicity in the preincubation assay. To each of 13 x 100-mm test tubes maintained at 37°C were added in the following order: 0.5 ml of S-9 mix or 0.1 M PO4 buffer (pH 7.4), 0.05 ml of the overnight culture, and 0.05 ml of solvent of chemical dilution. The mixture was mixed and allowed to incubate without shaking at 37°C for 20 minute, at which time 2.5 ml or 2.0 ml of molten (45°C) top agar supplemented with 0.5 mM L-histidine and 0.5 mM D-biotin were added. The contents of the tubes were mixed and poured onto 25 ml. of minimal glucose bottom agar in 15 x 100-mm plastic Petri dishes and Fisher Scientific plates. When the top agar had solidified, the plates were inverted an incubated at 37°C for 48 hr.

Concurrent solvent and positive controls were tested with and without the metabolic activation systems. At least five dose levels of the chemicals were tested, with three plates per dose level. All assays were repeated no less than 1 wk after the completion of the initial test.

Evaluation criteria:

1) mutagenic response: a dose-related, reproducible increase in the number of revertants over background even if the increase was less than
twofold, 2) nonmutagenic response: when no increase in the number of revertantts was elicited by the chemical and 3) questionable response: when there was an absence of a clear-cut dose-related increase in the number of revertants, when the dose-related increases in the number of revertants were not reproducible or when the response was of insufficient magnitude to support a determination of mutagenicity

Statistics:

Mean and Standard Error of the Mean was calculated.

Results and discussion

Test results

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:

When tested at the highest concentration of 10000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

At the highest dose tested there was a slight to complete clearing of the lawn indicating cytotoxicity at 10,000 ug/plate

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

At the highest dose tested there was a slight to complete clearing of the lawn indicating cytotoxicity at 10,000 ug/plate. DIPA was not mutagenic in any of the strains of S. Typhimurium tested up to 5,000 ug/plate with or without metabolic activation.

Strain TA1535:

Dose	No Activation (Negative)		No Activation (Negative)		No Activation (Negative)		10% HLI (Equivocal)		10% HLI (Negative)		10% RLI (Equivocal)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	64	4.5	24	1.2	27	2.3	9	2.1	11	0.7	11	2.1	14	4.6
100	51	8.1	22	2.4	27	5.5	9	2	11	1.5	9	1.3	10	1.5
333	39	4.4	24	1	25	2.6	12	1.2	7	1.9	10	1	8	0.9
1000	50	4.7	27	4.7	27	0.9	11	0.3	11	0.9	12	3.4	12	2.2
3333	36	4.7	18	1.9	28	2.4	15	0.7	9	0.9	12	2.3	10	1.9
10000	28S	4.3	12S	1.2	7S	2.9	24S	2.2	15S	0.6	22S	2.6	14S	1.5
Positive Control	1287	27.7	1228	29.6	736	47.3	160	15	161	1.9	143	10.3	151	7.1

Strain TA100:

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	162	9.8	128	2.6	113	6	123	5.6	115	8.7	109	8.9
100	169	13	120	7.8	86	6.4	121	7.5	97	2.2	123	4.1
333	180	7.5	125	5.1	100	5	119	9.3	122	11	124	4.1
1000	175	6.6	129	5.5	115	8.5	100	0.9	108	5	123	2.5
3333	164	6.7	115	7.2	102	0.6	105	8	122	14	123	8.4
10000	160S	5.6	112S	5.9	144S	12.1	127S	1.9	133S	7.3	128S	3.8
Positive Control	1453	7.6	1280	75.4	1198	46.4	1299	68.2	1821	72.7	567	58.9

Strain TA98:

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	17	3.4	18	2.8	30	3.5	27	3	25	2.9	29	0.9
100	19	0.9	17	1.8	26	3.5	23	3.5	28	1.2	31	1.7
333	20	2.1	16	2.1	26	2.7	27	0.3	33	3.6	29	1.5
1000	19	2	18	3.2	25	0.9	25	2.4	29	2.5	27	1.7
3333	25	1.5	14	0.9	23	3.2	32	2	24	2.6	29	2.1
10000	18S	1.2	14S	1.3	29S	4.7	28S	2.1	23S	3.7	23S	3.5
Positive Control	1590	5.4	928	22.7	957	14.7	932	31.7	1221	43.7	866	14.9

Strain TA1537:

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	9	1.5	7	0.3	5	1.8	8	1.2	7	2.6	5	1.3
100	6	1.2	4	0.7	7	1.5	5	0.9	8	1.2	5	2
333	8	2	5	1	6	0.9	9	0.3	5	1.2	4	1.3
1000	8	0.7	4	1.2	7	0.7	7	1.5	7C	1.5	8	1.2
3333	6	0.9	6	3.6	8	3	9	1.7	7	1.2	7	2
10000	7S	1.7	T		10S	0.9	5S	0.6	5S	1.9	7S	1
Positive Control	375	89.7	536	36.7	117	8.7	130	3.8	161	8.9	98	6.8

Abbreviations:
RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

DIPA was not mutagenic in any of the strains of S. Typhimurium tested up to 5,000 ug/plate.

Executive summary:

This publication includes data of Salmonella mutagenicity results on 270 coded chemicals, encompassing 329 tests performed by three laboratories under contract to the National Toxicology Program (NTP). The preincubation modification of the Salmonella mammalian microsome assay was used to test chemicals in up to five Salmonella strains in the presence and absence of rat and hamster liver S-9. With a few exceptions, inter- and intralaboratory reproducibility was good.

DIPA was not mutagenic in any of the strains of S. Typhimurium tested up to 5,000 ug/plate with or without metabolic activation. At higher concentrations inhibition of bacterial lawn growth was observed.