Benzophenone

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:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A standard NTP (National Toxicology Program) protocol. Equivalent to OECD 471.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1982

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 3

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(only four strains tested)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Benzophenone

EC Number:

204-337-6

EC Name:

Benzophenone

Cas Number:

119-61-9

Molecular formula:

C13H10O

IUPAC Name:

benzophenone

Details on test material:

- Name of test material (as cited in study report): Benzophenone

Method

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:

S9 mixture (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver)

Test concentrations with justification for top dose:

0 (control), 1, 3, 10, 33, 100, 166, 333 and 1000 µg/plate

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Controls 2

Positive controls:

yes

Remarks:

With metabolic activation

Positive control substance:

other: 2-aminoanthracene

Remarks:

Strains TA1537, TA98, TA100, TA1535

Controls 3

Positive controls:

yes

Remarks:

Without metabolic activation

Positive control substance:

9-aminoacridine

Remarks:

Strain TA1537

Controls 4

Positive controls:

yes

Remarks:

Without metabolic activation

Positive control substance:

sodium azide

Remarks:

Strains TA100, TA1535

Controls 5

Positive controls:

yes

Remarks:

Without metabolic activation

Positive control substance:

other: 4-nitro-o-penhylenediamine

Remarks:

Strain TA98

Details on test system and experimental conditions:

In the standard protocol (preincubation) for conducting the Ames assay, a test tube containing a suspension of one strain of Salmonella typhimurium plus S9 mix or plain buffer without S9, is incubated for 20 minutes at 37 ºC with the test chemical. Control cultures, with all the same ingredients except the test chemical, are also incubated. In addition, positive control cultures are prepared; these contain the particular bacterial tester strain under investigation, the various culture ingredients, and a known potent mutagen. After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium (Vogel-Bonner Medium. The plates are incubated, and bacterial colonies that do not require an excess of supplemental histidine appear and grow. These colonies are comprised of bacteria that have undergone reverse mutation to restore function of the histidine -manufacturing gene. The number of colonies is usually counted after 2 days.

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:

(stlight toxit at 1000 µg/plate in all strains with metabolic activation

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Benzophenone did not significatly increase the number of revertant colonies both in the absence or presence of a metabolic activation.
The substance was determined to be non-mutagenic under test conditions.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

TA100:

Dose	No Activation		No Activation		10% HLI		10% HLI		10% RLI		10% RLI
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	118	12.3	118	11.7	111	1.8	133	7.2	105	8.5	146	4.4
1	113	7.4
3	107	8.1	125	2.2	95	4.6	130	3.8
10	110	10.3	132	7.7	102	7.3	136	4.1	90	6.6	131	4.3
33	100	6.4	123	2.8	84	3.9	128	10.7	96	4.2	112	11.7
100	110	4.7	114	9.8	78	6.3	154	7	99	7.5	124	1.9
166			52s	7.5
333					80	4.1	117	8.7	86	7	90	6.6
1000									50s	6.1	35s	10.9
Positive Control	383	14.9	297	16.9	1784	26.1	2174	37.4	922	112.2	1638	60.4

 

TA1535

Dose	No Activation		No Activation		10% HLI		10% HLI		10% RLI		10% RLI
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	36	1.9	32	2.3	11	2.1	16	1.8	13	3.5	6	1.2
1	33	2.5
3	37	0.7	30	3.2	9	1.7	9	1.7
10	31	0.7	30	1.2	9	1.8	10	2.2	11	2.7	12	3
33	26	5.2	27	2	10	2.7	10	1.5	8	0.3	6	3.7
100	32	3.8	22	5.4	7	0.6	11	3	10	2.7	8	3.4
166			0s	0
333					6	1.5	8	0.9	8	2.7	5	0.3
1000									4	1	1s	0.9
Positive Control	395	21.7	404	28.2	492	17.2	691	15.2	211	18.1	535	23

 

TA1537

ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	4	0.9	7	0.3	9	0.9	7	0.6	7	0.3	6	1.2
1	6	2.1
3	5	0.7	5	1.8	8	2.3	7	2.4
10	4	0.9	7	0.6	5	1.2	8	2.6	6	1.2	5	0.7
33	6	1.7	6	1.2	7	1.5	8	2.3	6	1.2	13	2
100	4	0.3	5	1.8	7	1.8	8	2.7	8	0.6	8	0.6
166			2s	0.3
333					3	1.5	5	1.5	7	0.9	5	1.5
1000									4	1.8	3s	0.3
Positive Control	186	19.4	443	51.6	408	11.7	125	7.3	132	20.3	509	19.9

 

TA98

Dose	No Activation		No Activation		10% HLI		10% HLI		10% RLI		10% RLI
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	98	78	13	2.6	36	2.5	32	0	23	2.3	31	3.3
1	19	0.3
3	19	3.8	13	4.8	34	3.3	39	1.5
10	19	1.9	10	2.4	30	2.8	34	4.5	33	1.3	30	0.7
33	20	2.3	17	0.9	31	2.7	36	4.2	21	2.4	27	7.5
100	14	1.9	12	2.2	30	3.2	33	4.4	28	5.5	27	1.2
166			0s	0
333					23	1	15	1.2	25	4.5	14	3.2
1000									15	2.1	6s	0.3
Positive Control	475	5.4	431	38.4	1629	25.7	1901	39.4	867	11.9	1221	9.9

Abbreviations:

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

s = Slight Toxicity

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative (with and without metabolic activation)

Benzophenone did not significantly increase the number of revertant colonies both in the absence or presence of a metabolic activation. The substance was determined to be non-mutagenic under test conditions.

Executive summary:

A standard NTP (National Toxicology Program) protocol was performed to investigate the mutagenicity of benzophenone (test method equivalent to OECD 471). Different concentrations of test substance (from 100 to 10000 μg/plate) were tested in Salmonella typhimurium TA 1535, TA1537, TA100 and TA 98 by the preincubation assay (37°C, 20 min) with and without metabolic activation. Positive and negative controls confirmed the sensitivity of the test system. Benzophenone did not significantly increase the number of revertant colonies both in the absence or presence of a metabolic activation. The substance was determined to be non-mutagenic under test conditions.