Tetrachlorophthalic anhydride

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: scientifically acceptable study with restrictions. Neither Escherichia coli strain WP2 uvrA pKM101a nor S. typhimurium strain TA102 were employed in this study for the detection of oxidising mutagens and cross-linking agents.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity studies of tetrachlorophthalic anhydride (CAS No. 117-08-8) administered by gavage to F344/N Rats and B6C3F1 Mice.

Author:

NTP

Year:

1993

Bibliographic source:

NTP Technical Report Series No 28.

Reference 2

Reference Type:

publication

Title:

Mutagenicity testing of di(2-ethylhexyl)phthalate and related chemicals in Salmonella.

Author:

Zeiger E, Haworth S, Mortelmans K, Speck W

Year:

1985

Bibliographic source:

Environ Mutagen 7: 213-232

Materials and methods

Principles of method if other than guideline:

The study was conducted according to the Standard NTP protocol (Preincubation Assay) which is comparable to the method described in the publication by Mortelsman and Zeiger (Mutat Res. 20, 455, 1-2:29-60, 2000).

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachlorophthalic anhydride

EC Number:

204-171-4

EC Name:

Tetrachlorophthalic anhydride

Cas Number:

117-08-8

Molecular formula:

C8Cl4O3

IUPAC Name:

tetrachloro-1,3-dihydro-2-benzofuran-1,3-dione

Details on test material:

- Name of test material (as cited in study report): Tetrachlorophthalic anhydride
- Lot/batch No.: 2F03

Method

Target gene:

Salmonella typhimurium: histidine operon

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Liver homogenates from Aroclor 1254-induced male Sprague-Dawley rats (RLI) or male Syrian hamsters (HLI)

Test concentrations with justification for top dose:

0, 33.3, 100, 333.3, 1000, 3333.3, 6666.7 µg/plate

Vehicle / solvent:

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

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: sodium azide for TA1535 and TA100, 9-aminoacridine for TA1537, and 4-nitro-o-phenylenediamine for TA98

Remarks:

without S9 mix

Controls 2

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

with S9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation


METABOLIC ACTIVATION
The test was conducted with and without metabolic activation. In this study metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat and Syrian hamster liver were used. The percentage of S9 in the S9 mixture that was then added to cultures was 10 %.

Evaluation criteria:

A mutagenic response was defined as a reproducible, dose-related increase in the number of histidine-independent colonies over the spontaneous incidence; there was no requirement for a specific magnitude of increase.

Results and discussion

Test results

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:

cytotoxicity

Remarks:

from 3333.3 µg/plate

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The final dose level selection was based on the results of a preliminary range-finding study conducted with TA 100 in the presence and absence of S-9.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mean Reverants ± SEM in different strains

Strain: TA1535

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	25	3.1	15	1.5	15	1.9	7	0.9	9	0.3	8	1.5
33.3	14	1.2			16	2.3			9	2.5
100	17	1	17	1.2	11	2	12	3.3	9	1.7	7	1.3
333.3	20	0.7	20	4.3	11	1.5	6	1.2	11	2.7	9	0
1000	18	3.5	16	2.6	8	1.5	10	1.8	13	4.2	11	2.4
3333.3	13p	5.5	12s	1.7	9	2.9	9	1.5	8p	2.2	9	0.9
6666.7			t				7	1.5			6	3.5
Positive Control	444	17	338	21.3	458	3.3	340	27.4	374	12.8	321	21.4

Strain: TA 100

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	102	5.3	100	2.5	108	9.7	93	2.3	111	8.1	100	5.9
33.3	90	4.5			90	5.8			123	8.4
100	96	4	103	2.9	94	15.6	66	5.1	104	5.1	87	5.5
333.3	95	5.3	96	10.2	92	4.9	59	3.5	99	10.9	92	9.5
1000	82	5.5	75	8	75	3.6	59	4.5	110	8.2	99	0.9
3333.3	88p	1.2	56s	8.4	64	11.8	52	6.9	102p	1	75	0.7
6666.7			t				31	4.2			38s	3.7
Positive Control	526	12	358	15.3	1278	34.7	1953	36.1	627	18.2	823	37.4

Strain: TA98

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	16	1.5	26	4	46	4.2	29	2.1	34	3.1	36	2.3
33.3	13	3.5			35	1.5			29	2.1
100	13	3.5	25	3.1	33	6	38	2.7	33	6.8	34c	3.5
333.3	13	2.6	31	3.5	26	1.9	37	3.2	28	2.3	34	1.5
1000	18	1.5	27	1.3	26	0.3	35	5	27	3.5	37	2.1
3333.3	15	0.3	12	1.7	24	4.5	38	1.9	26p	3.8	28	2.6
6666.7			15s	3.1			32	2.9			26	4.3
Positive Control	615	9	738	59.5	1397	41.3	1596	54.6	798	62	847	64.9

Strain: TA1537

Dose	No Activation (Negative)		No Activation (Negative)		10% HLI (Negative)		10% HLI (Negative)		10% RLI (Negative)		10% RLI (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	16	1.5	7	1.7	24	1.7	16	1.3	24	4.3	16	0.9
33.3	9	0.7			26	1.3			24	4.3
100	6	1.9	8	0.9	24	1.8	12	2.1	21	2	12	2.4
333.3	9	1.5	8	0.9	28	1.2	12	1.5	29	1.8	12	2.6
1000	7	1.2	7	1	20	2.7	10	2.3	22	2.2	12	1.7
3333.3	6p	0.9	7s	0.9	14	1.2	9	2.4	27p	2.1	8	0.3
6666.7			0s	0			4	0.9			6	1.5
Positive Control	166	5.6	59	6.9	245	7.5	221	28	238	45.9	553	191.4

RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9
s = Slight Toxicity; T = Toxic