Isononanoic acid, mixed esters with dipentaerythritol, heptanoic acid and pentaerythritol

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:

23 Mar - 03 May 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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 (incl. QA statement)

Remarks:

Groupe Interministeriel des Produit Chimiques, France; Agence Française de Sécurité Sanitaire des Aliments (AFSSA), France

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

84418-63-3 (UVCB)

IUPAC Name:

84418-63-3 (UVCB)

Details on test material:

- Name of test material (as cited in study report): pentaisononanoate de dipentaerythritol
- Physical state: colourles viscous liquid
- Analytical purity: > 90%
- Purity test date: 22 March 2006
- Lot/batch No.: 05078603
- Expiration date of the lot/batch: 26 July 2006
- Storage condition of test material: RT

Method

Target gene:

his-operon

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254

Test concentrations with justification for top dose:

312.5, 625, 1250, 2500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9: sodium azide (1 μg/plate, TA1535 and TA100); 9-amino-acridine (50 µg/plate, TA 1537); 2-nitrofluorene (0.5 µg/plate, TA 98); mitomycin C (0.5 µg/plate, TA 102) +S9: 2-amino-anthracene (10 µg/plate, TA 102, 2 μg/plate, all other strains)

Remarks:

the positive controls were dissolved in DMSO, except for mitomycin C which was dissolved in distilled water

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation), experiment 1, with and without S9, experiment 2, without S9; preincubation, experiment 2, with S9
DURATION
- Exposure duration: 48 - 72 h

NUMBER OF REPLICATIONS: 3 replications each in 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: decrease in number of revertant colonies/thinning of bacterial lawn

Evaluation criteria:

Reproducible 2-fold (TA 98, TA 100, TA 102) or 3-fold (TA 1535, TA 1537) increase in number of revertants in comparison to the vehicle control and/or dose-response correlation.

Results and discussion

Test results

Test results 1

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:

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

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 102

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:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: moderate to marked emulsion at dose levels ≥ 1250 µg/plate

RANGE-FINDING/SCREENING STUDIES: Yes, no cytotoxicity up to the maximum of solubility

COMPARISON WITH HISTORICAL CONTROL DATA: valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Test results of experiment 1 (plate incorporation).

 

With or without S9-Mix	Test substance concentration (μg/plate)	Mean number of revertant colonies per plate (average of 3 plates ± standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA102	TA98	TA1537
–	vehicle (ethanol)	134 ± 9	25 ± 5	363 ± 21	27 ± 4	11 ± 5
–	312.5	98 ± 6	27 ± 4	330 ± 15	38 ± 15	8 ± 3
–	625	110 ± 20	35 ± 2	438 ± 91	44 ± 11	11 ± 3
–	1250	103 ± 14	30 ± 6	407 ± 93	34 ± 8	13 ± 6
–	2500	135 ± 22	31 ± 1	408 ± 22	31 ± 11	13 ± 4
–	5000	148 ± 63	31 ± 6	324 ± 16	32 ± 14	9 ± 3
Positive controls, –S9	Name	SA	SA	MMC	2NF	9AA
	Concentrations (μg/plate)	1.0	1.0	0.5	0.5	50
	Mean No. of colonies/plate (average of 3 ± SD)	877 ± 38	630 ± 74	2450 ± 103	171 ± 16	966 ± 27
+	vehicle (ethanol)	135 ± 22	30 ± 6	587 ± 10	44 ± 13	16 ± 6
+	312.5	130 ± 39	28 ± 9	533 ± 28	49 ± 4	9 ± 8
+	625	119 ± 6	26 ± 3	565 ± 21	49 ± 5	16 ± 10
+	1250	118 ± 7	28 ± 9	605 ± 38	43 ± 6	20 ± 9
+	2500	111 ± 6	27 ± 6	584 ± 97	43 ± 6	15 ± 6
+	5000	112 ± 5	34 ± 5	571 ± 29	43 ± 10	20 ± 5
Positive controls, +S9	Name	2AA	2AA	2AA	2AA	2AA
	Concentrations (μg/plate)	2.0	2.0	10	2.0	2.0
	Mean No. of colonies/plate (average of 3 ± SD)	1154 ± 180	419 ± 10	4419 ± 435	1208 ± 84	123 ± 16

SA: Sodium azide

9AA : 9-Aminoacridine

2NF : 2-Nitrofluorene

MMC: Mitomycine C

2AA: 2-Aminoanthracene

 

 

Table 2. Test results of experiment 2 (-S9: plate incorporation, +S9: pre-incubation).

With or without S9-Mix	Test substance concentration (μg/plate)	Mean number of revertant colonies per plate (average of 3 plates ± Standard deviation)
		Base-pair substitution type			Frameshift type
		TA 100	TA1535	TA102	TA98	TA1537
–	vehicle (ethanol)	126 ± 3	12 ± 5	343 ± 75	45 ± 14	6 ± 2
–	312.5	140 ± 17	15 ± 10	312 ± 40	25 ± 1	10 ± 1
–	625	183 ± 17	13 ± 6	454 ± 98	33 ± 3	8 ± 4
–	1250	153 ± 13	10 ± 4	317 ± 41	46 ± 9	5 ± 1
–	2500	144 ± 26	11 ± 4	359 ± 17	40 ± 13	5 ± 3
–	5000	175 ± 66	18 ± 44	420 ± 70	56 ± 18	8 ± 3
Positive controls, –S9	Name	SA	SA	MMC	2NF	9AA
	Concentrations (μg/plate)	1.0	1.0	0.5	0.5	50
	Mean No. of colonies/plate (average of 3 ± SD)	527 ± 83	711 ± 104	1258 ± 165	147 ± 22	1442 ± 287
+	vehicle (ethanol)	176 ± 7	9 ± 2	538 ± 13	43 ± 6	9 ± 2
+	312.5	145 ± 28	12 ± 3	728 ± 66	45 ± 3	10 ± 7
+	625	140 ± 21	19 ± 2	491 ± 41	35 ± 8	7 ± 1
+	1250	185 ± 16	11 ± 3	643 ± 128	30 ± 7	8 ± 2
+	2500	166 ± 16	14 ± 3	575 ± 11	35 ± 13	10 ± 4
+	5000	145 ± 22	16 ± 6	622 ± 74	43 ± 2	10 ± 5
Positive controls, +S9	Name	2AA	2AA	2AA	2AA	2AA
	Concentrations (μg/plate)	2.0	2.0	10	2.0	2.0
	Mean No. of colonies/plate (average of 3 ± SD)	705 ± 142	202 ± 25	2678 ± 1940	1259 ± 94	99 ± 27

SA: Sodium azide

9AA : 9-Aminoacridine

2NF : 2-Nitrofluorene

MMC: Mitomycine C

2AA: 2-Aminoanthracene

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative