Triisotridecyl benzene-1,2,4-tricarboxylate

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:

weight of evidence

Study period:

12 May - 22 Jun 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (only three Salmonella typhimurium strains tested)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(only 3 strains tested)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters

EC Number:

290-754-9

EC Name:

1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters

Cas Number:

90218-76-1

Molecular formula:

C33H51O6 to C39H66O6

IUPAC Name:

tris(mixed decyl and octyl)benzene-1,2,4-tricarboxylate

Constituent 2

Reference substance name:

1,2,4-Benzenetricarboxylic acid, decyl octyl ester

EC Number:

268-007-3

EC Name:

1,2,4-Benzenetricarboxylic acid, decyl octyl ester

Cas Number:

67989-23-5

Molecular formula:

C10H22O.xC9H6O6.xC8H18O

Details on test material:

- Name of test material (as cited in study report): [trade name]
- Substance type: product
- Physical state: liquid
- Analytical purity: no data
- Storage condition of test material: placed in a sealed secondary container, and stored desiccated at room temperature in the dark

Method

Target gene:

his operon

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 97

Additional strain / cell type characteristics:

other: histidine auxotrophe

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 98

Additional strain / cell type characteristics:

other: histidine auxotroph

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

other: histidine auxotroph

Metabolic activation:

with and without

Metabolic activation system:

rat liver post-mitochondrial fraction (S9) from Arochlor-1254 induced male Wistar rats

Test concentrations with justification for top dose:

0, 8, 40, 200, 1000 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: dimethylsulfoxide (DMSO)
- Justification for choice of solvent/vehicle: not stated

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-nitrofluorene (50 µg/plate) for TA 98; sodium azide (2 µg/plate) for TA 100; 9-aminoacridine (50 µg/plate) for TA 97

Remarks:

without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (5 µg/plate) with all strains

not specified

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Preincubation period: not applicable
- Exposure duration: 2 days


NUMBER OF REPLICATIONS: 3 (test substance), 5 (controls)


DETERMINATION OF CYTOTOXICITY
- Method: other: the background lawn was inspected for signs of toxicity (no further details mentioned)


OTHER:
- Colony counting: Colonies were counted electronically using a 40-10 image analyser (Analytical Measuring Systems).

Evaluation criteria:

- Validity criteria: a) negative control within the normal range, b) clear induced increase in revertant numbers by the positive control confirming discrimination between different strains and an active S9 preparation and c) no more than 5% loss of the plates due to contamination or unforeseen event
- Evaluation criteria: the test compound is considered mutagenic if a) the assay is valid and b) if it induces a two-fold and significant increase in revertant numbers, accompanied by dose response correlations

Statistics:

Analysis of variance (the F-test) and regression analysis were performed

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not measured
- Effects of osmolality: not applicable
- Evaporation from medium: not applicable
- Water solubility: not mentioned
- Precipitation: at 5000 µg/plate, this did not affect scoring of mutant colonies
- Other confounding effects: none


RANGE-FINDING/SCREENING STUDIES: An initial toxicity range-finding experiment was carried out in TA 100 only, using final concentrations at 8, 40, 200, 1000 and 5000 µg/plate plus a solvent and positive control. From these test results the highest test dose were chosen for the main mutation assay. There were no signs of toxicity up to 5000 µg/plate either in the absence and presence of S9.


COMPARISON WITH HISTORICAL CONTROL DATA: yes, the mean solvent control counts fell within the normal historical range.


ADDITIONAL INFORMATION ON CYTOTOXICITY: no cytotoxicity up to 5000 µg/plate in all strains

Remarks on result:

other: strain/cell type: Salmonella typhimurium

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table #: Number of revertants per plate (mean of 3 (test substance) resp. 5 (control) plates)

	[Strain TA 97]			[Strain TA 98]			[Strain TA 100]
Conc. [µg/plate]	¿ MA	+ MA	Cytotoxic (yes/no)	¿ MA	+ MA	Cytotoxic (yes/no)	¿ MA	+ MA	Cytotoxic (yes/no)
0*	85.4	157.4	no	19.8	23.0	no	90.2	126.6	no
8	76.7	143.7	no	15.7	22.7	no	82.3	125.3	no
40	83.0	137.7	no	24.3	33.0	no	97.0	140.0	no
200	80.0	159.0	no	22.3	29.7	no	93.0	136.7	no
1000	79.7	154.3	no	19.0	28.7	no	93.0	126.7	no
5000	86.7**	140.3**	no	15.7**	32.7**	no	95.0**	120.7**	no
Positive control	484.6	520.6	no	1224.2	940.8	no	536.0	675.8	no

*solvent control with DMSO ** precipitate observed

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative