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

Endpoint summary

Description of key information

Skin corrosion: Not corrosive 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 431.

Skin irritation: Not irritating 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 439.

Eye irritation: Not irritating 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 438.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

First the executive summaries of the in vitro skin irritation (OECD TG 439), skin corrosion (OECD TG 431) and eye irritation (OECD TG 438) performed with the major constituent, Ethyl-2‐methylpent‐3‐enoate, are presented and thereafter the read across justification.

Skin corrosion of Ethyl-2‐methylpent‐3‐enoate

In an in vitro skin corrosion test using a human skin model (EpiDerm Skin Model) performed according to OECD TG 431 and GLP principles, the influence of the test substance on the viability of human skin was tested. The test item was applied undiluted (50 μL) directly on top of the skin tissue. The positive control had a mean relative tissue viability of 7.2% after the 1-hour exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the acceptance limits of OECD 431 (lower acceptance limit ≥0.8 and upper acceptance limit ≤2.8) and the laboratory historical control data range. In the range of 20 - 100% viability the Coefficient of Variation between replicates of the negative control tissues was ≤ 14%, indicating that the test system functioned properly. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with the test item compared to the negative control tissues was 98% and 65%, respectively. Because the mean relative tissue viability for the test item was not below 50% after the 3-minute treatment and not below 15% after the 1-hour treatment the test item is considered to be not corrosive. In conclusion, the test substance is not corrosive to the skin.

Skin irritation of Ethyl-2‐methylpent‐3‐enoate

In an in vitro skin irritation test using a human skin model (EPISKIN Standard Model) performed according to OECD TG 439 and GLP principles, the influence of the test substance on the viability of human skin was tested. The test item was applied undiluted (25 μL), directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42 ± 1 hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed. Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 94%. Since the mean relative tissue viability for the test item was above 50% after 15 ± 0.5 minutes treatment the test item is considered to be non-irritant. The positive control had a mean cell viability of 5.4% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was ≤ 4.2%, indicating that the test system functioned properly. In conclusion, the test substance is not irritating to the skin.

Eye irritation of Ethyl-2‐methylpent‐3‐enoate

An Isolated Chicken Eye Test (ICET) was performed with the substance according to OECD guideline 438 and in accordance with GLP principles. Thirty µL of the Substance was applied to corneas (n=3). After 10 seconds exposure time, the surface of the eyes was rinsed with physiological saline solution. Slight corneal swelling change (mean = -8.5%) was observed during the four-hour observation period on test item treated eyes. Slight cornea opacity change (severity 0.5 on one eye and severity 1 on two eyes) was observed. No fluorescein retention change was noted on all eyes. No other morphological effect was observed. The negative control and positive control results were within the historical data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. Based on the results, the endpoints Corneal swelling and Corneal opacity were assigned ICE CLASS II and the Fluorescein retention endpoint was assigned ICE CLASS I. The substance is not an eye irritant.

Skin and eye irritation 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 skin and eye irritation 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 skin and eye irritation potential of Eth Oxanoate 369 Crude, the analogue approach is selected because for one of the constituents, Ethyl-2-methyl-3-pentenoate, reliable skin and eye irritation information are available which can be used for read-across.

Hypothesis: Eth Oxanoate 369 Crude has the same skin and eye irritation potential as Ethyl-2-methyl-3-pentenoate based on similarity in chemical structure, dermal absorption and reactivity.

Available information: For the major constituent (Ethyl-2‐methylpent‐3‐enoate), an in vitro skin irritation study (OECD TG 439) and an in vitro skin corrosion study (OECD TG 431) are available, both in compliance with GLP. Based on these studies the substance does not need to be classified for skin irritation. For this major constituent also an in vitro eye irritation study performed according to OECD TG 438 and in compliance with GLP resulting in absence of classification.

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 skin and eye irritation data are available.

Structural similarities and differences: The major constituent, Ethyl-2-methyl-3-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.

Bioavailability for skin and eye tissue: The bioavailability of the constituents of Eth Oxanoate 369 Crude and Ethyl-2-methyl-3-pentenoate are expected to be very comparable based on the similarity in chemical structure and physico-chemical properties.

Irritation reactivity: The Ethyl-2-methyl-3-pentenoate will have similar reactivity compared to the minor constituent, the double bond in its structure not conjugated to the ester and the reactivity will be similar to the saturated alkyl chain of the minor constituent.

Uncertainty of the prediction: There are no uncertainties other than those already addressed above. The information on the ECHA dissemination site of the minor constituent presents absence of classification and labelling for skin and eye irritation (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 skin and eye irritation for hazard and risk assessment

For Eth Oxanoate 369 Crude no skin and eye irritation data is available. For its major constituent Ethyl-2-methyl-3-pentenoate such information is available which can be used for read-across 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. For the analogue Ethyl-2-methyl-3-pentenoate, well conducted skin irritation, skin corrosion and eye irritation studies are available, showing no irritative or corrosive effects. This information can be directly used for read-across to Eth Oxanoate 369 Crude.

Final conclusion: Eth Oxanoate 369 Crude is not a skin or eye irritant.

Data matrix to support the read-across to Eth Oxanoate 369 Crude from Ethyl-2-methyl-3-pentenoate for skin and eye irritation

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		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 major constituent)*	2.54 (EPISUITE) 3.1 (measured)*	2.76 (EPISUITE) 2.09 (Echa dissemination site)
Water Solubility (mg/L)	612.3 (measured, major r constituent)	612.3 (measured)	467 (ECHA dissemination site
Human health endpoints
Skin corrosion	Read across from its major constituent	Negative (OECD TG 431)	Negative (ECHA dissemination site)
Skin irritation	Read across from its major constituent	Negative (OECD TG 439)	Negative (ECHA dissemination site)
Eye irritation	Read across from its major constituent	Negative (OECD TG 438, 2021)	Negative OECD TG 404 (ECHA dissemination site, 2012)
Skin sensitisation	Read across from its major constituent	Negative (OECD 442C, 2021) Negative (OECD 442D, 2021)	Not sensitising (ECHA dissemination site)

*the same substance is measured twice with log Kow 0.1 difference

Justification for classification or non-classification

Based on the results of the available in vitro skin and eye corrosion/irritation studies, the substance does not have to be classified for skin and eye irritation according to EU CLP (EC 1272/2008 and its amendments).