Sebacic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test substance was not mutagenic in the reverse bacterial mutation assay, performed according to Ames (Mut. Res., 31, 1975).

The analogue substance adipic acid (CAS: 124-04-9) was tested negative in the HPRT in vitro mammalian cell gene mutation test (according to OECD 476) and in the in vitro mammalian chromosome aberration test.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

GLP status unknown

Principles of method if other than guideline:

According to Ames et al., Mut. Res., 31, 1975

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Tokyo Kasei Kogyo Co. LTD. Tokyo, Japan

Target gene:

S. typhimurium: his-
E. coli: trp-

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Details on mammalian cell type (if applicable):

CELLS USED
- Type and source of cells:
S. typhimurium provided by B.N. Ames (USA)
E.coli provided by M. Ishizawa (Japan)

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

CELLS USED
- Type and source of cells:
S. typhimurium provided by B.N. Ames (USA)

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

1; 5; 10; 50; 100; 500; 1,000; 5,000 ug/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: without S9-mix: 2-(2 furyl)-3-(5-nitro-2-furyl) acrylamide, with S9-mix: 2-Aminoanthracene

Species / strain:

other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538 and E.coli WP2uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

True negative controls validity:

not applicable

Positive controls validity:

valid

Table 1: Mutagenic acitivities of the test substances and the positive control

Compound	Dose µg/plate	Revertant colonies/plate
		TA100		TA1535		WP3 uvrA		TA98		TA1537		TA1538
		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
Decanedioic acid	1	130	130	29	9	17	26	43	49	17	23	23	38
	5	119	138	34	11	24	22	52	50	13	25	26	38
	10	131	130	26	15	23	27	39	46	14	24	31	33
	50	125	123	34	13	18	24	47	56	11	24	27	33
	100	136	119	36	16	26	29	50	47	13	27	36	39
	500	140	122	28	13	24	32	42	56	11	18	20	36
	1,000	127	132	26	12	27	23	34	45	18	12	28	33
	5,000	112	134	36	14	24	27	45	47	12	20	30	32
Control
AF-2	0.01	501 ± 84.7	- b	-	-	-	-	-	-	-	-	-	-
	0.05	-	-	-	-	1,082± 293.7	-	278± 64.8	-	-	-	-	-
ENNG	5.0	-	-	1,101± 683.1	-	-	-	-	-	-	-	-	-
9-AC	80.0	-	-	-	-	-	-	-	-	889 ± 275.7	-	-	-
4-NQO	0.25	-	-	-	-	-	-	-	-	-	-	270 ± 66.2	-
B(a)P	5.0	-	1,084± 236.3	-	-	-	-	-	809± 108.4	-	313± 41.6	-	354± 89.4
2-AA	5.0	-	-	-	440± 198.6	-	359± 127.0	-	-	-	-	-	-

b: not tested

AF-2: 2-(2 furyl)-3-(5-nitro-2-furyl) acrylamide, ENNG: N-Ethyl-N'-nitro-N-nitrosoguanidine, 9 -AC: 9-Aminoacridine, 4 -NQO: 4-Nitroquinoline-l-oxide, B(a)P: Benzo(a)pyrene, 2-AA: 2-Aminoanthracene

Conclusions:

The test substance was not found mutagenic in the strains specified.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The justification for the type of information are discussed in the attached read-across document.

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

The justification for the type of information are discussed in the attached read-across document.

Reason / purpose for cross-reference:

read-across source

Species / strain:

mammalian cell line, other: human fibroblasts (WI-38)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 400 mg/L, preliminary cytotoxicity test

Untreated negative controls validity:

valid

Positive controls validity:

valid

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

The analogue substance adipic acid (CAS: 124-04-9) was tested negative in the in vivo mammalian chromosome aberration test.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Justification for type of information:

The justification for the type of information are discussed in the attached read-across document.

Reason / purpose for cross-reference:

read-across source

Sex:

male

Genotoxicity:

negative

Negative controls validity:

valid

Positive controls validity:

valid

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

IN VITRO:

In an Ames test, no mutagenicity was observered after exposure of S. typhimurium TA 1535, TA 1537, TA 98, TA 1538, TA 100, and E.coli WP2 uvrA with up to 5000 µg/plate of the test substance with or without metabolic activation. No cytotoxicity was observed within the used concentration range. Supportingly, in the supporting Ames test, similar results were obtained after exposure of S. typhimurim strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 with up to 5000 µg/plate with or without metabolic activation.

 

In vitro studies, using the structural analogon adipic acid, CAS 124-04-9 (for read-across justification see attached document):

In a mammalian chromosome aberration test, no abberation was observed after exposure of human embryonic lung fibroblast cells (WI-38) with up to 200 mg/L with the test substance, without metabolic activation. Cytotoxicity was observed at 400 mg/l. The positive and negative controls were functional.

In a mammalian cell gene mutation assay (GLP, according to OECD guideline 476) no biologically relevant increase of mutants was found after exposure of Chinese hamster lung fibroblasts (V79) with up to 10 mM test substance, with and without metabolic activation. No precipitation of the test item was noted in any experiment; no biological relevant growth inhibition was observed with and without metabolic activation. DMBA and EMS were used as positive controls and showed distinct and biologically relevant effects in mutation frequencies.

 

IN VIVO:

In vivo study with the structural analogon adipic acid, CAS 124-04-9 (for read-across justification see attached document):

In a chromosome abberation test (cited in OECD SIDS for dicarboxylic acid category, July 2001) male rats were gavaged with adipic acid; either once with up to 5000 mg/kg bw or once per day on 5 consecutive days with up to 2500 mg/kg bw. 200 - 500 metaphase chromosomes of bone marrow cells per dose were scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with more than 10 aberrations, polyploidy, pulverization and other chromosomal aberrations. The mitotic indices for all dose groups were considered to be within the normal limits of the controls and there was no evidence of chromosomal damage. The positive control groups, performed only during the acute studies, were functional.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008, as amended for the thirteenth time in Regulation (EU) No 2018/1480. As a result the substance is not considered to be classified for genotoxicity under Regulation (EC) No. 1272/2008.