Fatty acids, C18-unsatd., mono- and diesters with neopentylglycol and di-and triesters with trimethylolpropane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

May and June 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions (limited data on test substance available)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

limited data on test substance

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Deviations:

yes

Remarks:

limited data on test substance

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

limited data on test substance

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C14-18 and C18-unsatd., branched and linear, esters with trimethylolpropane

EC Number:

284-956-6

EC Name:

Fatty acids, C14-18 and C18-unsatd., branched and linear, esters with trimethylolpropane

Cas Number:

85005-23-8

IUPAC Name:

85005-23-8

Details on test material:

- Molecular formula (if other than submission substance): C9H11O6-R3 (approximately C60H116O6), R (cannot be quantified)
- Physical state: yellow liquid
- Analytical purity: not indicated, treated as 100% pure
- Lot/batch No.: N558876
- Storage condition of test material: at room temperature in the dark

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:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from rats treated with Aroclor

Test concentrations with justification for top dose:

3, 10, 33, 100, 333, 1000, 3330 and 5000 µg/plate

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535 (-S9 mix), 1µg/plate Migrated to IUCLID6: 1 µg/plate

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537 (-S9 mix), 60 µg/plate

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: daunomycine

Remarks:

TA98 (-S9 mix), 4 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

TA100 (-S9 mix), 650 µg/plate

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitroquinoline

Remarks:

WP2uvrA (-S9 mix) , 10 µg/plate

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

for all strains (+S9 mix); 1 µg/ plate (TA 1535, TA98, TA 100), 2.5 µg/plate (TA1537), 5 µg/plate (WP2 uvrA)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 h

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, but tested up to precipitating concentrations

Remarks:

at 3330 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 3330 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 3330 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 3330 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 3330 µg/plate and above

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY: No cytotoxicity was observed up to the maximum dose tested.
COMPARISON WITH HISTORICAL CONTROL DATA: The number of revertants for TA1537 and WP2 uvr A (+S9) were just outside the historical control range in the second experiment which was not considered to affect the validity of the study.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Results of experiment 1:

With or without S9-Mix	Test substance concentration (μg/plate)	Mean number of revertant colonies per plate (average of 3 plates)
		Base-pair substitution type			Frameshift type
		TA 1535	TA1537	TA98	TA100	WP2 uvrA
-	Vehicle^1	11	5	17	87	15
-	3				84	17
-	10				89	20
-	33	11	3	13	97	19
-	100	10	3	15	94	18
-	333	14	4	12	83	17
-	1000	13	4	17	103	19
-	3330^2	11	5	18	104	15
-	5000^2				98	16
Positive controls - S9	Name	SA	9AA	DM	MMS	4NQO
	Concentrations (μg/plate)	1	60	4	650	10
	Number of colonies/plate	332	590	603	844	1829
+	Vehicle^1	13	5	13	90	18
+	3				102	22
+	10				98	19
+	33	13	6	18	95	16
+	100	6	6	20	75	16
+	333	12	5	19	96	24
+	1000	16	7	14	102	17
+	3330^2	12	5	21	105	20
+	5000^2				91	17
Positive controls + S9	Name	2AA	2AA	2AA	2AA	2AA
	Concentrations (μg/plate)	1	2.5	1	1	5
	Number of colonies/plate	1594	227	1472	1273	734

1) 0.1 mL DMSO

2) precipitate visible

SA: sodium azide

4NQO: 4-nitroquinoline

9AA : 9-aminoacridine

DM : daunomycine

MMS: methylmethanesulfonate

2-AA: 2-aminoanthracene

 

 

Table 2: Results of experiment 2:

With or without S9-Mix	Test substance concentration (μg/plate)	Mean number of revertant colonies per plate (average of 3 plates)
		Base-pair substitution type			Frameshift type
		TA 1535	TA1537	TA98	TA100	WP2uvrA
-	Vehicle^1	7	5	17	74	22
-	33	7	2	15	76	19
-	100	6	5	11	72	22
-	333	7	6	17	76	20
-	1000	4	4	16	73	23
-	3330^2	7	6	17	79	13
Positive controls - S9	Name	SA	9AA	DM	MMS	4NQO
	Concentrations (μg/plate)	1	60	4	650	10
	Number of colonies/plate	230	266	788	793	1040
+	Vehicle^1	6	2	18	77	25
+	33	7	3	14	72	19
+	100	8	4	16	82	18
+	333	9	5	15	82	16
+	1000	6	5	16	75	18
+	3330^2	9	3	11	73	19
Positive controls + S9	Name	2AA	2AA	2AA	2AA	2AA
	Concentrations (μg/plate)	1	2.5	1	1	5
	Number of colonies/plate	224	466	1165	1874	303

1) 0.1 mL DMSO

2) precipitate visible

SA: sodium azide

4NQO: 4-nitroquinoline

9AA : 9-aminoacridine

DM : daunomycine

MMS: methylmethanesulfonate

2-AA: 2-aminoanthracene

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative