Dodecanoic acid, ester with 1,2,3-propanetriol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

17 Jan - 17 Aug 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted: 21 Jul 1997

Deviations:

no

GLP compliance:

yes

Remarks:

Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Mainz, Germany

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dodecanoic acid, ester with 1,2,3-propanetriol

Cas Number:

37318-95-9

Molecular formula:

C12 mono: C15H30O4 C12 di: C27H52O5 C12 tri: C39H74O6

IUPAC Name:

Dodecanoic acid, ester with 1,2,3-propanetriol

Method

Target gene:

his operon

Species / strain

Species / strain / cell type:

other: TA1535, TA102, TA100, TA98 and TA97a

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with 500 mg Aroclor 1254/kg body weight intra-peritoneally

Test concentrations with justification for top dose:

Dose-range-finding experiments
Experiment 1c:
50, 150, 500, 1500 and 5000 µg/plate with and without metabolic activation
Experiment 1d:
0.05, 0.15, 0.5, 1.5, 5 and 15 µg/plate with and without metabolic activation

Main experiments
Experiment 1e:
0.05, 0.15, 0.5, 1.5, 5 and 15 µg/plate with and without metabolic activation
Experiment 2b:
0.23, 0.47, 0.94, 1.88, 3.75, 7.5 and 15 µg/plate with and without metabolic activation

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: The solvent was chosen because of the solubility of the test substance in the vehicle and the relative nontoxicity of the vehicle to the bacteria evaluated in a pre-experiment.

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

demineralised water, DMSO and ethanol (including solvents for positive controls)

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: see below

Details on test system and experimental conditions:

Experiments 1a, 1b and 2a were declared invalid and were therefore not reported here.

METHOD OF APPLICATION: Experiment 1e: in agar (plate incorporation); Experiment 2b: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3 replications per experiment

DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of spontaneous revertants and reduction in bacterial background lawn

Evaluation criteria:

A substance is considered to have mutagenic potential, if a reproducible increase of revertant colonies per plate exceeding an increase factor of 2 in at least one strain can be observed. A concentration-related increase over the range tested is also taken as a sign of mutagenic activity.

Statistics:

Mean values and standard deviation were calculated.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Exp 1e and 2b: at 15 µg/plate in all strains +/- S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No precipitation of the test item was observed up to 5000 µg/plate

RANGE-FINDING/SCREENING STUDIES: In the dose range finding studies cytotoxicity was observed in all strains from 15 µg/plate.

Any other information on results incl. tables

Table 1. Mean revertants Experiment 1e

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Demin. water	Mean	83	69	52	50	82	102	356	345	24	22
	sd	6.7	5	5.2	10.7	20.6	18.5	62.9	72.6	8	7.5
DMSO	Mean	85	78	43	39	110	101	257	324	21	21
	sd	5.6	13.6	5.5	11.9	6	21.2	26.6	20.8	0.6	5.3
Ethanol	Mean	78	70	47	39	107	127	292	258	23	22
	sd	11	5.9	3.8	10.7	6.4	3.1	58.9	24	3.6	3.1
Positive	Mean	343	657	560	487	404	1001	689	1083	265	132
Controls*	sd	35.9	24.1	146	123.3	17.4	0	60.2	400	59.5	15.2
	f(I)	4.04	8.42	13.02	12.49	4.93	9.91	2.68	3.34	11.04	6.29
15 µg/plate	Mean	14	21	2	4	22	17	165	149	1	2
	sd	6	7.2	1.2	1.7	9	4	16.8	20.2	0	1.2
	f(I)	0.18	0.3	0.04	0.1	0.21	0.13	0.57	0.58	0.04	0.09
5 µg/plate	Mean	116	68	26	37	97	86	311	387	16	21
	sd	15.6	15.7	3.5	13.7	13.5	10	49.4	31.1	4.4	1.7
	f(I)	1.49	0.97	0.55	0.95	0.91	0.68	1.07	1.5	0.7	0.95
1.5 µg/plate	Mean	84	90	32	43	104	97	309	356	25	19
	sd	2.1	18.7	8.1	11.4	26.5	8.1	32.6	69.3	4.4	2.9
	f(I)	1.08	1.29	0.68	1.1	0.97	0.76	1.06	1.38	1.09	0.86
0.5 µg/plate	Mean	82	83	30	37	94	93	360	432	18	22
	sd	12.1	25.2	9.6	6.8	9.1	14.7	34.2	52.5	2.6	1.2
	f(I)	1.05	1.19	0.64	0.95	0.88	0.73	1.23	1.67	0.78	1
0.15 µg/plate	Mean	76	86	28	40	103	92	312	259	22	22
	sd	11.9	4.4	1.5	3.2	18	10.4	60.5	78.2	3.8	3.5
	f(I)	0.97	1.23	0.6	1.03	0.96	0.72	1.07	1	0.96	1
0.05 µg/plate	Mean	79	95	27	38	103	123	337	305	25	21
	sd	25.7	21.7	6.7	10	33.8	5.8	14	98	5.6	4
	f(I)	1.01	1.36	0.57	0.97	0.96	0.97	1.15	1.18	1.09	0.95

 f(I) = increase factor

* Different positive controls were used

Table 2. Mean revertants Experiment 2b

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Demin. water	Mean	83	91	33	36	88	100	289	348	17	19
	sd	8.7	5.6	5.3	5	3	15	12.2	25	6.8	3.8
DMSO	Mean	96	89	30	39	99	98	336	295	18	15
	sd	13.9	18.7	4.4	2.1	16.3	9.2	32.7	73.2	1.7	3.2
Ethanol	Mean	73	103	37	37	83	95	280	316	15	15
	sd	2.6	7	10.2	7.6	10.4	15	62.9	63.5	3.6	4.2
Positive	Mean	338	533	493	260	579	897	1235	1251	457	157
Controls*	sd	31	50.3	188.7	10.6	83.3	180.7	364.5	226.9	55.5	9.2
	f(I)	3.52	5.99	16.43	6.67	6.58	9.15	3.68	4.24	26.88	10.47
15 µg/plate	Mean	10	3	1	2	3	2	18	63	3	2
	sd	1.7	1.5	0	1	0	1	1.2	20.3	4	1.2
	f(I)	0.14	0.03	0.03	0.05	0.04	0.02	0.06	0.2	0.2	0.13
7.5 µg/plate	Mean	83	82	32	36	83	98	243	273	16	21
	sd	5.8	20.5	4.4	1.2	5.8	10.5	20.5	45.1	4.4	1.5
	f(I)	1.14	0.8	0.86	0.97	1	1.03	0.87	0.86	1.07	1.4
3.75 µg/plate	Mean	94	85	30	32	81	100	247	275	15	14
	sd	6.7	4.2	6.1	7.8	7.8	3.1	46.4	74.6	2.1	1.5
	f(I)	1.29	0.83	0.81	0.86	0.98	1.05	0.88	0.87	1	0.93
1.88 µg/plate	Mean	78	91	32	31	92	102	335	224	14	18
	sd	10.4	12.1	1.7	4.6	9.2	6.1	8.3	2	4.6	4
	f(I)	1.07	0.88	0.86	0.84	1.11	1.07	1.2	0.71	0.93	1.2
0.94 µg/plate	Mean	95	99	30	44	85	90	223	244	16	10
	sd	11	11.1	8.3	10.1	13.8	8.5	62	10.6	2.5	0.6
	f(I)	1.3	0.96	0.81	1.19	1.02	0.95	0.8	0.77	1.07	0.67
0.47 µg/plate	Mean	107	110	36	33	82	95	205	239	18	12
	sd	4.6	17.1	4	4.7	6.9	11.4	36.3	84.3	1	1.7
	f(I)	1.47	1.07	0.97	0.89	0.99	1	0.73	0.76	1.2	0.8
0.23 µg/plate	Mean	89	76	31	36	85	88	209	249	14	11
	sd	15	12.5	6	6.2	14	15.3	48.1	14	2	1
	f(I)	1.22	0.74	0.84	0.97	1.02	0.93	0.75	0.79	0.93	0.73

 f(I) = increase factor

* Different positive controls were used

Applicant's summary and conclusion

Conclusions:

Under the conditions of the Ames test the substance was not mutagenic in any of the five bacterial strains (TA1535, TA98, TA100, TA102 and TA97a) tested with and without metabolic activation.