Reaction products of fatty acid chlorides, C8-12 (even numbered) with glycine and sodium hydroxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of fatty acid chlorides, C8-12 (even numbered) with glycine and sodium hydroxide

EC Number:

940-223-9

Molecular formula:

C10H18NO3Na C12H22NO3Na C14H26NO3Na

IUPAC Name:

Reaction products of fatty acid chlorides, C8-12 (even numbered) with glycine and sodium hydroxide

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

S9 homogenate

Test concentrations with justification for top dose:

0.025, 0.05, 0.1 mg/ml
Precipitation at 0.15 mg/ml

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

APPENDIX 1.INDIVIDUAL DATA OF PERCENTAGE MITOTIC INDEX FOR INITIAL CYTOTOXICITY TEST

Set No.	Treatment	Dose (µL/mL)	Replicate	Metaphases	Blast cells	Mitotic index	Percentage Mitotic index
1 (+S9) (3-5hours)	Negative control	-	1	37	997	0.0358	3.58
			2	34	1006	0.0327	3.27
	Vehicle control	-	1	34	1003	0.0328	3.28
			2	35	1000	0.0338	3.38
	Hostapon SLG	0.1	1	31	1004	0.0299	3.00
			2	33	1023	0.0313	3.13
		0.05	1	29	1011	0.0279	2.79
			2	34	1001	0.0329	3.29
		0.025	1	34	1020	0.0323	3.23
			2	33	1007	0.0317	3.17
2 (-S9) (3-5 hours)	Negative control	-	1	37	1007	0.0354	3.54
			2	36	991	0.0351	3.51
	VC	-	1	36	1007	0.0345	3.45
			2	37	1006	0.0355	3.55
	Hostapon SLG	0.1	1	33	1002	0.0319	3.19
			2	32	1002	0.0309	3.09
		0.05	1	33	1008	0.0317	3.17
			2	34	1035	0.0318	3.18
		0.025	1	43	1209	0.0343	3.43
			2	36	1039	0.0335	3.35
3 (-S9) (18-20 hours)	Negative control	-	1	40	1122	0.0344	3.44
			2	40	1023	0.0376	3.76
	VC	-	1	40	1048	0.0368	3.68
			2	38	1028	0.0356	3.56
	Hostapon SLG	0.1	1	37	1010	0.0353	3.53
			2	37	1035	0.0345	3.45
		0.05	1	38	1007	0.0364	3.64
			2	35	1015	0.0333	3.33
		0.025	1	37	1003	0.0356	3.56
			2	36	1003	0.0346	3.46

APPENDIX 2.INDIVIDUAL DATA OFCHROMOSOMAL ABERRATIONAND MITOTIC INDEX

Set No.	Treatment	Dose (µL/mL)	Replicate	Mitotic Index				Aberrations									Total No. of Aberrations	Total No. of Aberrations without Gaps	Total % of Aberrated cells
								GAP		Break		Exchange		Fragments	Ring	Deletion
				Total No. of MP	Total No. of Blast cells	Mitotic Index	Percentage of MI	Chromatid	Chromosome	Chromatid	Chromosome	Chromatid	Chromosome
1 (+S9) (3-5 hours)	Negative control	-	R1	37	968	0.0368	3.68	-	-	-	-	-	-	-	-	-	-	-	-
			R2	35	971	0.0348	3.48	-	-	-	-	-	-	-	-	-	-	-	-
	Vehicle control	-	R1	36	973	0.0357	3.57	-	-	-	-	-	-	-	-	-	-	-	-
			R2	36	966	0.0359	3.59	-	-	-	-	-	-	-	-	-	-	-	-
	Positive control (Cyclophosphamide )	10 µg/mL	R1	32	997	0.0311	3.11	-	-	1	-	1	0	2	1	5	10	10	9
			R2	33	972	0.0328	3.28	-	-	1	3	0	0	1	1	3	9	9	8
	Hostapon SLG	0.025	R1	34	979	0.0336	3.36	-	-	-	-	-	-	-	-	-	-	-	-
			R2	34	988	0.0330	3.33	-	-	-	-	-	-	-	-	-	-	-	-
		0.05	R1	32	971	0.0319	3.19	-	-	-	-	-	-	-	-	-	-	-	-
			R2	33	1010	0.0316	3.16	-	-	-	-	-	-	-	-	-	-	-	-
		0.1	R1	31	983	0.0306	3.06	-	-	-	-	-	-	-	-	-	-	-	-
			R2	31	993	0.0303	3.03	-	-	-	-	-	-	-	-	-	-	-	-

APPENDIX 2(Contd..,). INDIVIDUAL DATA OFCHROMOSOMAL ABERRATIONAND MITOTIC INDEX

Set No.	Treatment	Dose (µL/mL)	Replicate	Mitotic Index				Aberrations										Total No. of Aberrations	Total No. of Aberrations without Gaps	Total % of Aberrated cells
								GAP		Break		Exchange		Fragments	Ring	Deletion	Others*
				Total No. of MP	Total No. of Blast cells	Mitotic Index	Percentage of MI	Chromatid	Chromosome	Chromatid	Chromosome	Chromatid	Chromosome
2 (-S9) (3-5 hours)	Negative control	-	R1	37	1012	0.0353	3.53	-	-	-	-	-	-	-	-	-		-	-	-
			R2	35	965	0.0350	3.50	-	-	-	-	-	-	-	-	-		-	-	-
	Vehicle control	-	R1	34	981	0.0335	3.35	-	-	-	-	-	-	-	-	-		-	-	-
			R2	33	968	0.0330	3.30	-	-	-	-	-	-	-	-	-		-	-	-
	Positive Control (Mitomycin C)	0.05 µg/mL	R1	32	982	0.0316	3.16	2	-	1	-	-	-	3	1	3	2	12	10	8
			R2	33	988	0.0323	3.23	2	3	1	2	-	-	-	1	1	3**	12	10	6
	Hostapon SLG	0.025	R1	33	993	0.0322	3.22	-	-	-	-	-	-	-	-	-		-	-	-
			R2	34	1006	0.0327	3.27	-	-	-	-	-	-	-	-	-		-	-	-
		0.05	R1	31	971	0.0309	3.09	-	-	-	-	-	-	-	-	-		-	-	-
			R2	32	1002	0.0319	3.19	-	-	-	-	-	-	-	-	-		-	-	-
		0.1	R1	32	1023	0.0303	3.03	-	-	-	-	-	-	-	-	-		-	-	-
			R2	32	1019	0.0304	3.04	-	-	-	-	-	-	-	-	-		-	-	-

APPENDIX 2(Contd..,). INDIVIDUAL DATA OFCHROMOSOMAL ABERRATIONAND MITOTIC INDEX

Set No.	Treatment	Dose (µL/mL)	Replicate	Mitotic Index						Aberrations									Total No. of aberrations	Total No. of aberrations without gaps	Total % of aberrated cells
								GAP			Break		Exchange		Fragment	Ring	Deletion	Endoreduplication
				Total No. of MP	Total No. of Blast cells	Mitotic Index	Percentage of MI	Chromatid	Chromosome		Chromatid	Chromosome	Chromatid	Chromosome
3 (-S9) (18-20 hours)	Negative control	-	R1	36	990	0.0351	3.51	-	-		-	-	-	-	-	-	-	-	-	-	-
			R2	37	1020	0.0350	3.50	-	-		-	-	-	-	-	-	-	-	-	-	-
	Vehicle control	-	R1	34	975	0.0337	3.37	-	-		-	-	-	-	-	-	-	-	-	-	-
			R2	35	977	0.0346	3.46	-	-		-	-	-	-	-	-	-	-	-	-	-
	Positive Control (Mitomycin C)	0.05 µg/mL	R1	33	974	0.0334	3.34	-	4		2	3	-	-	1	1	4	-	15	11	9
			R2	34	984	0.0324	3.24	4	-		-	2	-	-	3	1	1	1	12	8	5
	Hostapon SLG	0.025	R1	34	982	0.0335	3.35	-	-		-	-	-	-	-	-	-	-	-	-	-
			R2	34	973	0.0338	3.38	-	-		-	-	-	-	-	-	-	-	-	-	-
		0.05	R1	32	979	0.0317	3.17	-	-		-	-	-	-	-	-	-	-	-	-	-
			R2	33	982	0.0325	3.25	-	-		-	-	-	-	-	-	-	-	-	-	-
		0.1	R1	31	988	0.0304	3.04	-	-		-	-	-	-	-	-	-	-	-	-	-
			R2	32	984	0.0315	3.15	-	-		-	-	-	-	-	-	-	-	-	-	-

Applicant's summary and conclusion

Conclusions:

Not clastogenic

Executive summary:

Hostapon SLG was investigated according to the Guideline OECD 473 (version 1997). CHO cells were treated with the test substance with and without metabolic activation at concentrations of 0.025, 0.05 and 0.1 mg/ml. The concentration of 0.15 mg/l was associated with enhanced precipitation. Negative results were obtained in two indenpendent experiments. Hostapon SLG is not clastogenic in in-vitro assay.