1,1',1''-nitrilotripropan-2-ol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Salmonella Mutagenicity Tests: III. Results From the Testing of 225 Chemicals

Author:

Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W

Year:

1987

Bibliographic source:

Environmental Mutagenesis 9 (Suppl 9), 1-110

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

No E.coli strain or TA102 requested in the OECD471 version then in force

Principles of method if other than guideline:

Haworth S, Lawlor T, Mortelmans K, Speck W, Zeiger E (1983): Salmonella mutagenicity results for 250 chemicals. Environ Mutagen S[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',1''-nitrilotripropan-2-ol

EC Number:

204-528-4

EC Name:

1,1',1''-nitrilotripropan-2-ol

Cas Number:

122-20-3

Molecular formula:

C9H21NO3

IUPAC Name:

1-[bis(2-hydroxypropyl)amino]propan-2-ol

Specific details on test material used for the study:

Purity > 94%

Method

Target gene:

His locus

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced male Sprague-Dawley rats and Syrian hamsters S9-mix

Test concentrations with justification for top dose:

0, 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:

9-aminoacridine

sodium azide

other: 4-nitro-o-phenylene diamine: TA 98, without S9-mix; 2-aminoanthracene: all strains, with S9-mix

Details on test system and experimental conditions:

The test chemical (0.05 mL), Salmonella culture (0.10 mL), and S-9 mix or buffer (0.50 mL) were incubated at 37°C, without shaking, for 20 min. The top agar was added and the contents of the tubes were mixed and poured onto the surface of petri dishes containing Vogel-Bonner medium. The histidine-independent (his+) colonies arising on these plates were counted following two days incubation at 37°C. Plates were machine counted unless precipitate was present which interfered with the count, or the color of the test chemical on the plate reduced the contrast between the colonies and the background agar.

Evaluation criteria:

Evaluations were made at both the individual trial and overall chemical levels. Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable (?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “ +W,” if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response, and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach
twofold over background for a chemical to be judged mutagenic. A chemical was judged mutagenic (+) or weakly mutagenic (+ W) if it produced a reproducible dose-related reponse over the solvent control in replicate trials.
A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a “+W” response, or if only single doses produced increases in his+ revertants in repeat trials. Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response.

Statistics:

no data

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

other: not required by OECD471 version then in force

Cytotoxicity / choice of top concentrations:

other: not required by OECD471 version then in force

Additional information on results:

Triisopropanolame was negative (non-mutagenic) in all assays with and without metabolic activation.

Any other information on results incl. tables

Strain TA1535

Dose	No Activation (Negative)		10% HLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	42	3.8	21	2.7	11	1.3
100	33	1.2	13	1.9	13	0.3
333	34	1.9	15	1.2	15	2.3
1000	32	6.4	13	0.3	12	4.6
3333	24	3.5	16	1.8	11	1
10000	28	5.5	15	0.3	10	0.9
Positive Control	1162	4.5	115	9.1	99	0.9

 

Strain TA100 

Dose	No Activation (Negative)		10% HLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	151	9	141	0.7	151	10.2
100	141	9	147	4.8	139	0.6
333	131	0.6	141	5.6	146	2.4
1000	144	8.6	146	3.2	149	4.3
3333	152	5	151	10.3	143	7.9
10000	148	2.5	146	4.7	139	5.8
Positive Control	1406	62.8	1040	19.8	1025	37.8

 

Strain TA98 

Dose	No Activation (Negative)		10% HLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	20	1	26	4.5	30	1.9
100	19	1.8	28	0.9	33	4.9
333	19	2.9	31	1.5	29	2
1000	21	0	31	4.1	30	0.9
3333	15	0.9	31	4.3	30	0.6
10000	16	3.1	28	1.2	25	2.3
Positive Control	1320	21.1	864	24.3	697	11.5

 

Strain TA1537 

Dose	No Activation (Negative)		10% HLI (Negative)		10% RLI (Negative)
Dose units	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	8	0.3	8	0.7	6	2.3
100	4	0.6	7	1	10	2.9
333	6	0.6	11	3.2	9	0.6
1000	8	0.9	11	1.8	9	2
3333	6	1.3	10	1.5	8	1.7
10000	7	0.3	11	0.6	10	0.9
Positive Control	282	11.2	88	7	82	6

 

Abbreviations:
RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9