Pentadecan-15-olide

Endpoint summary

Additional information

Table 7.6/1: Summary of genotoxicity tests

Test n°	Test / Guideline Reliability	Focus	Strains / cells tested	Metabolic activation	Test concentration	Statement
1   Tzan King, 2001	Ames Test (OECD 471) K, rel. 1	Gene mutation	TA 1535 TA 1537 TA 98 TA 100 TA 102	-S9 +S9	Up to 5000 µg/plate	-S9 : non mutagenic +S9 : non mutagenic
2   Abramsson, 2002	Ames Test S, rel. 4	Gene mutation	TA 97 TA 98 TA 100	-S9 +S9	Up to 1300 µg/plate	-S9 : non mutagenic +S9 : non mutagenic
3 (RA)   Thompson, 2005	Ames Test (OECD 471) S, rel. 2	Gene mutation	TA 1535 TA 1537 TA 98 TA 100 WP2 uvrA	-S9 +S9	Up to 5000 µg/plate	-S9 : non mutagenic +S9 : non mutagenic
4 (RA)   Sokolowski, 2005	Ames Test (OECD 471) S, rel. 2	Gene mutation	TA 1535 TA 1537 TA 98 TA 100 TA 102	-S9 +S9	Up to 5000 µg/plate	-S9 : non mutagenic +S9 : non mutagenic
5 (RA)   Durward & Nolan, 2001	ML/TK test (OECD 476) K, rel. 2	Gene mutation	mouse lymphoma L5178Y cells	-S9 +S9	Up to cytotoxic concentration	-S9 : non mutagenic +S9 : non mutagenic
6   Abramsson, 2002	In vivo micronucleus (eq. OECD 474) WoE, rel. 2	Chromosomal aberration	PCE from peripheral blood	n.a.	M: Up to 1600 mg/kg bw/d F: Up to 1400 mg/kg bw/d	Non clastogenic, non aneugenic
7 (RA)   Schulz, 2005	HL CAT (OECD 473) WoE, rel. 2	Chromosomal aberration	Human Lymphocytes	-S9 +S9	Up to cytotoxic concentrations (-S9) or precipitating concentrations (+S9)	-S9 : non clastogenic +S9 : non clastogenic
8 (RA)   Durward, 1995	HL CAT (OECD 473) WoE, rel. 2	Chromosomal aberration	Human Lymphocytes	-S9 +S9	Up cytotoxic concentrations	-S9 : non clastogenic +S9 : non clastogenic

Gene mutation Assays (Tests n° 1-5):

Two Bacterial Reverse mutation Assays (Ames test) were conducted with the substance (See Table 1). Test n°1, conducted according to OECD test guideline No 471 and in compliance with GLP, was selected as the key study. Test 2 was used as supporting data because only three strains of bacteria were used. No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains in both tests, with any dose of the test material, either with or without metabolic activation. Both tests indicate that the substance does not induce gene mutations in bacteria whereas all positive control chemicals (with and without metabolic activation) induced significant increase of colonies. This result is also supported by two Ames tests, conducted on the supporting substance (EC 422 -320 -3) (Test n°3 and 4, see Iuclid Section 13 for read-across justification). The substance is therefore considered as non-mutagenic according to the Ames test.

Inability to produce gene mutation was confirmed in mammals using an in vitro forward mutation assay in mouse lymphoma TK L5178Y cells (ML/TK test) (Test n°5) conducted on the supporting substance (EC 422 -320 -3). None of the dose levels up to the cytotoxicity limit, either with or without metabolic activation, induced significant mutant frequency increases in the initial or repeat tests. The supporting substance (EC 422 -320 -3) does not induce forward mutations at the TK locus in L5l78Y mouse lymphoma cells under activation and non-activation conditions whereas both positive control chemicals (with and without metabolic activation) induced significant mutant frequency increases. The supporting substance (EC 422 -320 -3) is therefore considered as negative for inducing forward mutations at the TK locus in L5178Y mouse lymphoma cells under activation and non-activation conditions used in this assay. This result confirms the results of the Ames tests and extends the non-mutagenic effect of the substance to mammalian cells.

Chromosomal aberration (Test n°6-8)

The clastogenic and aneugenic potential of the substance was determined using an in vivo mammalian erythrocytes micronucleus assay (Test n°6), which measured the potential of a substance to increase the incidence of the structural and numerical chromosome aberrations in mice bone marrow erythrocytes. None of the dose level, up to the dose of 1600 mg/kg bw in males or 1400 mg/kg bw in females, induced increase in the frequency of micronucleated polychromatic erythrocytes (fMPCE) in bone marrow, whereas positive control chemical induced significant increase in the fMPCE. The substance was therefore considered as negative for inducing chromosomal aberrations in mice bone marrow erythrocytes under the conditions used in this study. This result is also supported by two in vitro chromosome aberration tests in Chinese hamster lung fibroblast, conducted on the supporting substance (EC 422 -320 -3) (Test n°7 and 8). In both tests, none of the dose levels up to the cytotoxicity or precipitating limit, either in the presence of absence of metabolic activation, induced significant increases in the frequency of cells with aberrations.

The substance is therefore considered as non-clastogenic and non-aneugenic.

Justification for selection of genetic toxicity endpoint
No study was selected since all the studies were negative.

Short description of key information:
- Ames Test (OECD 471, GLP, K, rel. 1): non mutagenic up to cytotoxic concentrations in S. typhimurium TA 1535, TA 1537, TA 98, TA 100, and TA102.
- MLA/TK Forward Mutation Assay with a Confirmatory Assay (OECD 476, GLP, K, rel. 2): non mutagenic up to cytotoxicity limit on the supporting substance.
- In vivo micronucleus (eq. OECD 474, WoE rel. 2): no increased in MPCE + Human lymphocyte chromosome aberration test (OECD 473, GLP, WoE, rel. 2): non clastogenic up to cytotoxic limit / precipitating concentration on the supporting substance.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification for human health according to the Regulation (EC) No. 1272/2008 including the ATP3.

Self classification:

Based on the available information, no additional classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.