Sodium tris(1,2-naphthoquinone 1-oximato-O,O')ferrate(1-)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication

Data source

Reference

Reference Type:

publication

Title:

Evaluation of Subchronic (13 Week), Reproductive, and in Vitro Genetic Toxicity Potential of 2-Ethylhexyl-2-cyano-3,3-diphenyl Acrylate (Octocrylene)

Author:

Odio RM et al.

Year:

1994

Bibliographic source:

Fund Appl Toxicol 22: 355-368.1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

To evaluate the mutation potential of Octocrylene in mammalian cell by mammalian cell gene mutation assay.

GLP compliance:

not specified

Type of assay:

other: mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Octocrilene

EC Number:

228-250-8

EC Name:

Octocrilene

Cas Number:

6197-30-4

Molecular formula:

C24H27NO2

IUPAC Name:

2-ethylhexyl 2-cyano-3,3-diphenylacrylate

Details on test material:

- Name of test material (as cited in study report): Octocrylene
- Molecular formula: C24H27NO2
- Molecular weight: 361.482
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material (as cited in study report): Octocrylene
- Molecular formula: C24H27NO2
- Molecular weight: 361.482
- Substance type: Organic

Method

Target gene:

thymidine kinase locus in L5178Y mouse lymphoma

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: mouse lymphoma L5178Y TK+/_ cells supplied by Dr.Donald clive (Research Triangle park ,NC)

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data available

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S-9

Test concentrations with justification for top dose:

28 - 380 µg/ml ( without S-9)6.7 - 89 µg/ml (with S-9)

Vehicle / solvent:

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

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

other: DMBA (with metabolic activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 24, 48 h

NUMBER OF CELLS EVALUATED: 200 cells/plate

DETERMINATION OF CYTOTOXICITY - Method: relative total growth

Rationale for test conditions:

No data available.

Evaluation criteria:

Doubling of mutant frequency above control

Statistics:

Yes ,standard deviation was observed.

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

Additional information on results
RANGE-FINDING/SCREENING STUDIES: A preliminary study was conducted in mouse lymphoma L5178Y cells .The cells were exposed to eight concentration of test material ranging from 5-10000 µg /ml for 4 hour in the presence and absence of metabolic activator. From the
Preliminary study high concentration was selected 0.38mg/ml and 0.089 mg/ml for the cloning assay to be done in the presence and absence of metabolic activator.

Remarks on result:

other: No increase in mutant frequency above solvent control was observed with the test substance in both the presence and absence of metabolic activation. The respective positive controls produced the expected significantly elevated mutant frequency.

Any other information on results incl. tables

Mutant frequency inMouse lymphoma L5178Y TK^+/_cells exposed in vitro to Octocrylene (No metabolic activation)

	Compound	Concentration (µg/ml)	Colonies/viable TFT plate^b	Colonies/viable Count/plate^c	Mutant frequency^d	Relative total growth^e
1	Control(DMSO)	1%v/v	23±4	171±7	27	-
2	Octocrylene	0.38	20±1	83±11	48	6
		0.28	21±3	104±3	40	9
		0.21	26±3	118±3	44	12
		0.16	29±9	128±7	45	13
		0.12	25±0	130±8	38	14
		0.089	24±1	132±13	36	18
		0.067	26±3	144±12	36	20
		0.050	27±4	148±11	36	23
		0.038	21±3	136±8	31	27
		0.028	22±2	167±11	26	50
3	EMS	0.500	272±10	85±5	640*	30
		0.250	209±12	123±3	340*	54

 

 

Mutant frequency in Mouse lymphoma L5178Y TK+/_ cells exposed in vitro to Octocrylene (No metabolic activation)

	Compound	Concentration (µg/ml	Colonies/viable TFT plate^b	Colonies/viable Count/plate^c	Mutant frequency^d	Relative total growth^e
1	Control(DMSO)	1%v/v	27±2	160±8	34	-
2	Octocrylene	0.089	23±2	137±6	34	9
		0.067	22±3	134±6	33	28
		0.050	19±3	150±7	25	58
		0.038	21±3	163±7	26	94
		0.028	23±1	154±7	30	96
		0.021	21±2	150±5	28	97
		0.016	26±3	143±3	36	91
		0.012	24±4	166±8	29	99
		0.0089	26±4	152±11	34	96
		0.0067	27±2	169±15	32	105
	EMS	0.500	140±3	76±6	368*	25
		0.250	107±10	133±9	161*	72

b; Cells plated in TFT containing medium; data are means ± Standard deviation of two or three plates

c; Cells plated in TFT free medium medium for viability determination ; data are means ± Standard deviation of two or three plates.

d; Mutant frequencies are reported as number of mutant per 10⁶Surviving cell.

e; Relative total growth was determined as (%growth in suspension phase /% growth cloner phase) 100.Clonal phage growth determined from viable count plate.

 *Significant different from vehicle control

 

 

 

 

 

 

 

 

 

 

b; Cells plated in TFT containing medium; data are means ± Standard deviation of two or three plates

c; Cells plated in TFT free medium medium for viability determination ; data are means ± Standard deviation of two or three plates.

D; Mutant frequencies are reported as number of mutant per 10⁶Surviving cell.

E; Relative total growth was determined as (%growth in suspension phase /% growth cloner phase) 100.Clonal phage growth determined from viable count plate.

 

 

*Significant different from vehicle control

Applicant's summary and conclusion

Conclusions:

Octocrylene was observed for its mutagenic potential in mammalian cell. The test material was considered to be negative for mutagenic effect in the presence and absence of metabolic activator in Mouse lymphoma L5178Y TK+/_ cells.

Executive summary:

In genetox study Octocrylene (6197-30-4) was assessed for its possible mutagenic potential. For this purpose mammalian cell gene mutation assay was performed inmouse lymphoma L5178Y TK^+/_cells ,using a test substance concentration28 - 380 µg/ml ( without S-9)6.7 - 89 µg/ml (with S-9). Cytotoxicity was also observed by relative total growth method. No significant mutagenic effects were observed for Octocrylenein the presence and absence of metabolic activator in Mouse lymphoma L5178Y TK^+/_cells. Therefore Octocrylene (6197-30-4) was considered to be non mutagenic with and without metabolic activator in Mouse lymphoma L5178Y TK^+/_cells.