ETHYL 2-METHYL-4-PENTANOATEETH OXANOATE-369 CRUDE

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test: Negative for Eth Oxanoate 369 Crude based on read across from Ethyl 2-methyl-3-pentenoate, which was tested in a study according to OECD TG 471

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

The executive summary of the in vitro genetic toxicty study (OECD TG 471) performed with the major constituent, Ethyl-2‐methylpent‐3‐enoate, is presented and thereafter the read across justification.

Ames test

The substance is tested in the Ames test according to OECD TG 471 and following GLP. The test was performed in two independent experiments, at first a direct plate assay was performed and secondly a pre-incubation assay. The following concentrations were tested: 52, 164, 512, 1600 and 5000 μg/plate in experiment 1; 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate (without S9-mix); 52, 164, 512, 1600 and 5000 μg/plate (with S9-mix) in experiment 2. In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. The test item did not induce a dose-related increase in the number of revertant colonies in each of the five tester strains (TA1535, TA1537, TA98 and TA100 WP2uvrA) both in the absence and presence of S9-metabolic activation. Based on this the substance is not mutagenic in this test.

Genotoxicity (Ames test) of Eth Oxanoate 369 Crude based on read-across from data available for Ethyl-2-methyl-3-pentenoate (CAS# 58625-89-1), its main constituent

Introduction and hypothesis for the analogue approach

The multi-constituent substance Eth Oxanoate 369 Crude consists of two main constituents: 62% Ethyl-2-methyl-3-pentenoate (CAS# 58625-89-1) and 32% Ethyl-2‐methylpentanoate (CAS# 39255-32-8). For Eth Oxanoate 369 Crude, no experimental genotoxicity data are available. In accordance with Article 13 of REACH, lacking information can be generated by means other than experimental testing, i.e. applying alternative methods such as, QSARs, grouping and read-across. For assessing the genotoxicity of Eth Oxanoate 369 Crude, the analogue approach is selected because for one of the constituents, Ethyl-2-methyl-3-pentenoate, reliable genotoxicity information is available which can be used for read-across.

Hypothesis: Eth Oxanoate 369 Crude has the same genotoxic potential as Ethyl-2-methyl-3-pentenoate based on similar chemical structure, physico-chemical properties and genotoxic reactivity.

Available information: For the major constituent (Ethyl-2‐methylpent‐3‐enoate), an Ames test according to OECD TG 471 with GLP has been performed. The test substance did not induce a dose-related increase in the number of revertant colonies in each of the five tester strains (Salmonella typhimurium TA1535, TA1537, TA98, TA100 and Escherichia coli WP2uvrA) both in the absence and presence of S9-metabolic activation.

Target chemical and source chemical

Chemical structures of the target chemical and the source chemical are shown in the data matrix, including physico-chemical properties.

Purity / Impurities

The major and minor constituents of Eth Oxanoate 369 Crude are presented in the Data matrix. The impurities of Eth Oxanoate 369 Crude are <10%.

Analogue approach justification

According to Annex XI 1.5, read-across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read-across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation, which is presented below.

Analogue selection: For Eth Oxanoate 369 Crude, the constituent Ethyl-2-methyl-3-pentenoate was selected as source chemical for read-across because it is the major constituent (62%) of Eth Oxanoate 369 Crude and experimental genotoxicity data is available.

Structural similarities and differences: The major constituent, Ethyl-2-methyl-3-pentenoate has a  molecular weight of 142 g/mol and has a similar structure to the minor constituent (32%), Ethyl-2‐methylpentanoate, which has a molecular weight of 144 g/mol. The only difference in their structures is that Ethyl-2-methyl-3-pentenoate has a double bond on the carbon 3 of the pentene ester.

Toxico-kinetic:  The bioavailability of the constituents of Eth Oxanoate 369 Crude and Ethyl-2-methyl-3-pentenoate are very similar based on similarities in chemical structures, water solubility and log Kow.  

Genotoxic reactivity: The reactivity of Eth Oxanoate 369 Crude  is similar to its major constituent, Ethyl-2-methyl-3-pentenoate. The unsaturation in its alkyl chian is not considered more reactive compared to the saturated chain of the minor constituent because the unsaturated bond is not conjugated .

Remaining uncertainties: There are no uncertainties other than those already addressed in the previous sections. The available in vitro Ames (OECD TG 471) performed with the minor constituent (32%), Ethyl-2‐methylpentanoate was also negative for the Ames test (ECHA disseminated dossier: (https://echa.europa.eu/nl/registration-dossier/-/registered-dossier/10528) further supports the read across.

Data matrix The relevant information on physico-chemical properties and toxicological characteristics are presented in the data matrix below.

Conclusions on genotoxicity for hazard and risk assessment

For Eth Oxanoate 369 Crude no Ames test (OECD TG 471) is available. Read-across from its main constituent, Ethyl-2-methyl-3-pentenoate, is used to fill this data gap. When using read-across, the result derived should be applicable for C&L and/or risk assessment, and be presented with adequate and reliable documentation. This documentation is presented in the current text. The Ames test (OECD TG 471) for Ethyl-2-methyl-3-pentenoate showed no genotoxic potential. Based on this information, it is concluded that Eth Oxanoate 369 is negative for the Ames test.

Final conclusion: Eth Oxanoate 369 Crude is not genotoxic.

Data matrix to support the read-across to Eth Oxanoate 369 Crude from Ethyl-2-methyl-3-pentenoate for genotoxicity

Endpoint	Eth Oxanoate 369 Crude	Ethyl-2-methyl-3-pentenoate	Ethyl-2‐methylpentanoate
	Target	Major constituent Source	Minor constituent
Chemical structure
CAS number	Not applicable	58625-89-1	39255-32-8
EC number	952-991-2	854-058-4	254-384-1
Typical conc. (%)	Not applicable	62	32
REACH registered	-	Registered	Registered
Empirical formula	Not applicable	C8H14O2	C8H16O2
Molecular weight	142 - 144	142	144
Phys-chem
Log Kow	3.0 (measured: main constituent)*	2.54 (EPISUITE) 3.1 (measured)*	2.76 (EPISUITE) 2.09 (ECHA dissemination site)
Water Solubility (mg/L)	612.3 (measured: main constituent),	612.3 (measured)	467 (ECHA dissemination site)
Human health endpoints
Ames (Gene mutations in bacterial cells)	Read across from main constituent	Negative (OECD 471)	Negative (ECHA dissemination site),

* the same substance is measured with a log Kow difference of 0.1

Justification for classification or non-classification

Based on the results of the Ames test, the substance does not have to be classified for genotoxicity according to EU CLP (EC 1272/2008 and its amendments).