Ethyl palmitate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the available studies performed on the source substances of the category, none of the assessed substances showed mutagenicity effect on bacteria strain. According to CLP criteria and the category approach, the test item Ethyl Palmitate was considered to be not mutagenic for bacteria strain.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

See attached report on section 0 Categories and assessment report section 13 for justification and rationale of the category approach.

Key result

Species / strain:

other: S typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. Coli WP2 uvr A

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:

not applicable

Positive controls validity:

valid

Table 1: Results from key studies performed on the source substances of the category

Common name	CAS	Fatty acid chain length	Type of alcohol	MW	Appareance	In vitro gene mutation study in bacteria (Ames test)
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	Experimental result: Negative
Isopropyl palmitate	142-91-6	C16	Isopropanol	298.51	Liquid	no data
Ethyl linoleate	544-53-4	C18:2	ethanol	308,5	Liquid	Experimental result: Negative
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	no data
Fatty acids, C16-18, butyl esters	85408-76-0	C16-18	Butanol	312.53 – 340.58	Paste	no data
Fatty acids, C16-18 and C18-unsatured, isobutyl esters	84988-79-4	C16-18, C18:1	Isobutanol	312.53 – 340.58	Liquid	no data
Isopropyl isostearate	68171-33-5	C18iso	Isopropanol	326.56	Liquid	no data

 

Several Ames test were performed according to OECD 471 guideline. This stain used bacterial strain lines as Salmonella Typhimurium and E.Coli. .These tests were performed on the isopropyl myristate and ethyl linoleate, both of these substances did not showed mutagenicity. The two substances showed structural and physic chemical similarities with the target substance the ethyl palmitate. It can be stated that the ethyl palmitate followed same mutagenic property with source substances of the category on bacteria. Hence, the ethyl palmitate was not considered as mutagenic for bacteria.

Conclusions:

Based on the category approach and according to the results of the available studies of the source substances, the target substance was considered to be not mutagenic on bacteria strain.

Executive summary:

According to the Regulation (EC) NO. 1907/2006, Annex XI, 1.5, A Read-Across Category was performed in order to provide informations on the Ethyl Palmitate.

This category was based on common and shared physico-chemical and structural properties as:

- common functional group,

- common precursors and the likehood of common impurities as well as common breakdown products via biological processes, which are chemically structurally similar, and

- constant pattern in the changing of the potency of the properties across the category.

Based structural and physic chemical similarities (fatty acids linked with esters), the toxicological profiles between the members of the category are expected to be the same on bacteria strain.

Hence, the members of the category were not considered as mutagenix for bacteria strain.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The category group covers alcohol linked with fatty acid chains unsatured and satured. This category includes monoconstituent chemicals and UVCB substances varying acid chain length (C14 to C18) and based on alcohol function type (including ethanol, butanol and isopropanol). This approach was performed in order to provide sufficient information for physicochemical, ecotoxicological and toxicological characterizations of the ethyl palmitate. Based on structural and physic-chemicals similarities, available experimental studies from source chemicals could be used for the target substance ethyl palmitate.

This category group includes:

-       Isopropyl myristate                                                 CAS 110-27-0

-       Isopropyl palmitate                                                 CAS 142-91-6

-       Ethyl linoleate                                                         CAS 544-35-4

-       Ethyl oleate                                                            CAS 111 -62-6

-       Fatty acids, C16 -18, butyl esters                          CAS 85408-76-0

-       Fatty acids, C16 -18 and C18-unsatured isobutyl esters              CAS 84988-79-4

-       Isopropyl isostearate                                                                     CAS 68171-33-5

-       Target substance : Ethyl palmitate                                                  CAS 628-97-7

In accordance with article 13 (1) of Regulation (EC) No. 1907.2006, “information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular for human toxicity, environmental fate and ecotoxicity, information shall be generated whenever possible by means other than vertebrate animal tests which includes the use of information from structurally related substances (grouping or read across)”. Therefore, the available experimental data were collected and evaluated according to Annex XI requirements.

Summary of the available studies for bacteria mutagenicity potential

Isopropyl myristate CAS 110-27-0

Two Ames test were performed in order to evaluate the potential mutagenicity on bacteria strain. The key study was performed according to OECD Guideline 471 (bacterial reverse mutation test) and GLP compliance. E. Coli WP2 uvr 1, S. Typhimurium TA 1535, TA 1537, TA98 and TA 100 were evaluated with and without metabolic activation system, up to 5000 µg/plate during 48 hours. Ethanol was used as vehicle. Number of revertant colony and cytotoxicity were evaluated. No mutagenicity was observed.

The supporting study was performed on S. Typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538 with and without metabolic activation system. The test item concentrations used were 4, 20, 100, 500 and 2500 µg/plate, acetone was used as vehicle. Control and positive control were used. Test item was applied in plate incorporation method. Revertant colony was counted. No increase of revertant colony was observed. According to CLP criteria and the two available studies, the Isopropyl myristate was not considered as mutagenic on bacteria strain.

Ethyl linoleate CAS 544 -35-4

An mouse lymphoma assay was performed on the ethyl linoleate in order to assess the potential mutagenicity of the substance on mammalian cells. The experimental study was performed according to OECD TG 476 method, using mouse lymphoma L5178Y cells. The cells were incubated in medium with test substance at different concentrations up to 300 µg/mL during 3 hours in a first experiment and 24 hours in a second experiment. Metabolic activation system was used or not. After 2 days on expression time, cells were selected with trifluorothymidine during 12 days. Cytotoxicity was evaluated too. No significant increase in the mutation frequency at the TK locus was observed after treatment with ethyl linoleate either in the absence or in the presence of metabolic activation system.

A chromosome aberration test was performed according to OECD TG 473 method. Cultured peripheral human lymphocytes were used and exposed up to 333 µg/mL in a first experiment for 3 hours. In a second experiment, cells were exposed up to 800 µg/mL for 24 hours with and without metabolic activation system with 48 hours fixation time. The vehicle used was DMSO. Cyclophosphamide and mitomycin C were used as positive control. Both in the absence and presence of metabolic activation system, the ethyl linoleate did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations.

Justification for classification or non-classification

Based on the available studies performed on the source substances of the category, none of the assessed substances showed mutagenicity effect on bacteria strain. According to CLP criteria and the category approach, the test item Ethyl Palmitate was considered to be not mutagenic for bacteria strain.