6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphtamide

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted study, performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9 mix (purchased from Oriental Yeast Co, Ltd.)

Test concentrations with justification for top dose:

Dose range-finding study: 0 (negative control). 4.88, 19.5, 78.1, 313, 1250 and 5000 micrograms/plate.
Main study: 0 (negative control), 156, 313, 625, 1250, 2500 and 5000 micrograms/plate.

Vehicle / solvent:

- Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: Test substance was not soluble in distilled water (at 50 mg/l) but was soluble in DMSO (at 50mg/ml). A 50 mg/ml test substance solution with DMSO was prepared and determined to be stable (no change in colour or exothermic reaction).

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

other: DMSO (solvent) treatment assumed for negative controls

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene (2AA); 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2); Sodium azide (NaN3); 2-Methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine.2HCl (ICR-191)

Details on test system and experimental conditions:

Plates were pre-incubated at 37 +/- 0.5 degrees C for 20 minutes and then incubated at 37 +/- 0.5 degrees C for 48 hours. Colonies were counted manually and mechanically (for plates where test material precipitation was observed, colonies were counted manually, otherwise plates were counted with a colony analyzer - CA-11D, System Science Ltd.).

Results and discussion

Test results

Test results 1

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

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:

no cytotoxicity

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

See table 1 in 'Any other information on results' field

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Main test

With or without S9 mix	Test substance dose (ug/plate)	Number of revertant colonies per plate
		Base-pair substitution type						Frameshift type
		TA100	Mean	TA1535	Mean	WP2uvrA	Mean	TA98	Mean	TA1537	Mean
Without S9	Negative control	103	102	12	10	19	21	16	21	16	13
		98		16		23		21		13
		104		3		20		26		10
	156	128	116	5	9	34	30	34	29	10	9
		104		12		25		23		7
	313*	78	99	11	11	18	19	20	17	9	8
		119		11		20		14		6
	625*	98	96	13	11	23	23	23	20	8	6
		93		9		23		17		3
	1250*	97	98	16	10	31	30	13	17	7	7
		99		4		28		20		7
	2500*	87	98	22	14	15	15	18	17	9	8
		109		5		15		15		7
	5000*	104	103	7	6	19	19	14	20	7	7
		101		5		18		26		6
With S9	Negative control	99	103	4	8	34	32	31	32	16	18
		115		14		36		28		23
		95		5		25		36		15
	156	110	107	12	12	26	30	29	30	19	17
		103		12		33		30		15
	313	117	119	14	13	38	31	30	34	19	23
		120		12		23		38		27
	625	121	116	10	8	42	38	26	30	27	27
		110		5		33		34		27
	1250*	117	127	8	9	30	30	20	22	27	25
		137		9		30		24		22
	2500*	126	113	6	8	21	27	27	24	28	24
		100		10		32		20		19
	5000*	102	104	5	7	24	27	23	27	15	16
		106		9		29		30		16
Positive control without S9	Chemical	AF-2		NaN3		AF-2		AF-2		ICR-191
	Dose (ug/plate)	0.01		0.5		0.01		0.1		0.5
	No. of revertants colonies/plate	629	625	350	330	280	259	485	482	1284	1350
		621		310		237		478		1416
Positive control with S9	Chemical	2AA		2AA		2AA		2AA		2AA
	Dose (ug/plate)	1		2		10		0.5		2
	No. of revertants colonies/plate	1063	1035	249	248	657	691	265	253	226	209
		1007		247		724		240		191

* Precipitate of test substance was observed in all plates for each test strain

2-Aminoanthracene (2AA); 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2); Sodium azide (NaN3); 2-Methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine.2HCl (ICR-191)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Under the conditions of this study, S-DHMN gave a negative response in S.typhimurium strains TA1535, TA1537, TA98 and TA100 and E.coli strain WP2uvrA in both the presence and absence of S9-mix.