Registration Dossier

Environmental fate & pathways

Endpoint summary

Administrative data

Description of key information

Additional information

Justification for grouping of substances and read-across

The short chain methyl esters category (SCAE Me) covers fatty acid esters of methanol. The category contains both mono-constituent substances, with fatty acid C-chain lengths ranging from C6 to C18 and UVCB substances, composed of single methyl esters in variable proportions. Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. methanol) with a fatty acid (e.g. lauric acid) in the presence of an acid catalyst (Radzi et al., 2005). The esterification reaction is started by the transfer of a proton from the acid catalyst to the acid to form an alkyloxonium ion. The carboxylic acid is protonated on its carbonyl oxygen followed by a nucleophilic addition of a molecule of the alcohol to the carbonyl carbon of the acid. An intermediate product is formed. This intermediate product loses a water molecule and proton to give an ester (Liu et al., 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Monoesters are the final products of esterification of fatty acids with methanol.

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, 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are allocated to the category of SCAE Me.

The SCAE Me category members include:

CAS

EC name

MW

Fatty acid chain length

Type of alcohol

Molecular formula

106-70-7 (a)

Methyl hexanoate

130.18

C6

Methanol

C7H14O2

111-11-5

Methyl octanoate

158.24

C8

Methanol

C9H18O2

110-42-9

Methyl decanoate

186.29

C10

Methanol

C11H22O2

111-82-0

Methyl laurate

214.35

C12

Methanol

C13H26O2

124-10-7 (b)

Methyl myristate

242.41

C14

Methanol

C15H30O2

112-39-0

Methyl palmitate

270.46

C16

Methanol

C17H34O2

112-62-9

Methyl oleate

296.49

C18:1 (cis)

Methanol

C19H36O2

112-63-0

Methyl linoleate

294.48

C18:2 (cis)

Methanol

C19H34O2

112-61-8

Methyl stearate

298.51

C18

Methanol

C19H38O2

68937-83-7

Fatty acids, C6-10, methyl esters

130.18-186.29

C6-10

Methanol

C7H14O2; C11H22O2

67762-39-4

Fatty acids, C6-12, methyl esters

130.18-214.35

C6-12

Methanol

C7H14O2; C13H26O2

85566-26-3

Fatty acids, C8-10, methyl esters

158.24-186.29

C8-10

Methanol

C9H18O2; C11H22O2

67762-40-7

Fatty acids, C10-16, methyl esters

186.29-270.46

C10-16

Methanol

C11H22O2; C17H34O2

61788-59-8

Fatty acids, coco, methyl esters

214.35-242.40

C12-14

Methanol

C13H26O2; C15H30O2

308065-15-8

Fatty acids, C12-14 (even numbered), methyl esters

214.35-242.40

C12-14

Methanol

C13H26O2: C15H30O2

1234694-02-0

Fatty acids, C12-16 (even numbered) and C18-unsatd., methyl esters

270.46-296.49

C16-18; C18uns.

Methanol

C17H34O2; C19H38O2; C19H36O2

68937-84-8

Fatty acids, C12-18, methyl esters

214.35-296.49

C12-18

Methanol

C13H26O2; C19H38O2

67762-26-9

Fatty acids, C14-18 and C16-18-unsatd., methyl esters

242.40-298.51

C14-18; C16-18uns.

Methanol

C15H30O2; C19H38O2; C17H32O2; C19H36O2

61788-61-2

Fatty acids, tallow, methyl esters

270.46-298.51

C16-18; C18:1

Methanol

C17H34O2; C19H38O2; C19H36O2

67762-38-3

Fatty acids, C16-18 and C18-unsatd., methyl esters

270.46-298.51

C16-18; C18uns.

Methanol

C17H34O2; C19H38O2; C19H36O2

85586-21-6

Fatty acids, C16-18, methyl esters

270.46–298.51

C16-18

Methanol

C17H34O2; C19H38O2

111-62-6 (c)

Ethyl oleate

310.52

C18:1 (cis)

Ethanol

C20H38O2

544-35-4 (c)

Ethyl linoleate

308.51

C18:2 (cis)

Ethanol

C20H36O2

68171-33-5 (c)

Isopropyl isostearate

326.56

C18iso

Iso-propanol

C21H42O2

123-95-5 (c)

Butyl stearate

340.60

C18

Butanol

C22H44O2

22047-49-0 (c)

2-ethylhexyl stearate

396.70

C18

2-ethyl-hexanol

C26H52O2

91031-48-0 (c)

Fatty acids, C16-18, 2-ethylhexyl esters

368.65-396.70

C16-18

2-ethyl-hexanol

C24H48O2; C26H52O2

57-10-3 (c)

Palmitic acid

256.43

C16

--

C16H32O2

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

(c)Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco‑)toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

 

Grouping of substances into this category is based on:

(1) common functional groups:

All category members are esters with the ester group being the common functional group of all substances. The substances are monoesters of aliphatic alcohols (methanol) and fatty acids with the chain length C6 to C18 and C18 unsaturated. The fatty acid chains comprise carbon chain lengths ranging from C6 (e.g. methyl hexanoate, CAS 106-70-7) to C18 (e.g. methyl stearate, CAS 112-61-8), mainly saturated but also mono and di unsaturated C18 (e.g. methyl oleate, CAS 112-62-9 and methyl linoleate, CAS 112‑63‑0).

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals:

All members of the category result from esterification of the alcohol with the respective fatty acid(s). Esterification is, in principle, a reversible reaction (hydrolysis). Thus, the alcohol and fatty acid moieties are simultaneously precursors and breakdown products of the category members. For the purpose of grouping of substances, enzymatic hydrolysis in the gastrointestinal tract and/or liver is identified as the biological process, by which the breakdown of the category members result in structurally similar chemicals. Following hydrolysis, fatty acids are enzymatically degraded primarily via beta-oxidation. Alternative oxidation pathways (alpha- and omega-oxidation) are available and are relevant for degradation of branched fatty acids. Unsaturated fatty acids require additional isomerization prior to enter the beta-oxidation cycle. The methanol is slowly oxidized in the liver by the enzyme alcohol dehydrogenase (ADH) to formaldehyde, which itself is oxidized very rapidly by the enzyme aldehyde dehydrogenase (ALDH) to formic acid. Finally, formic acid is slowly metabolised to CO2 and H2O (ICPS, 2002).

(3) constant pattern in the changing of the potency of the properties across the category:

a) Physicochemical properties:

The molecular weight of the category members ranges from 130.19 to 298.5 g/mol. The physical appearance is related to the chain length of the fatty acid moiety and the degree of saturation. Thus, methyl esters up to a fatty acid chain length of C12 are liquid, the C14 methyl ester (methyl myristate, CAS 124-10-7) is a semi solid substance, methyl esters with fatty acid chain lengths of C16 and C18 are solids (methyl palmitate and methyl stearate, CAS 112-39-0 and 112-61-8). Methyl esters with unsaturated fatty acids (C18:1, C18:2) are liquid (methyl oleate and methyl linoleate, CAS 112-62-9 and 112-63-0). For all category members the vapour pressure decreases with the chain length from 496 Pa (C6 methyl ester) to circa 0.002 Pa (C18 methyl ester), for C18 unsaturated esters it is even lower. The octanol/water partition coefficient increases with increasing fatty acid chain length, ranging from log Kow = 2.34 (C6) to log Kow = 8.35 (C18), for C18 unsaturated log Kow = 7.45 (C18:1) and 6.82 (C18:2) respectively. This trend can be observed also of the water solubility where 1330 mg/L for C6 methyl ester to 0.003 mg/L for C18 methyl ester is measured. The solubility of C18 unsaturated esters are slightly higher than for saturated components. It is observed that interactions between molecules of different single substances in water result in a decrease of water solubility comparing with water solubilities of mono-constituents, e.g. for C8-C10 it is 0.3 mg/L, while for C8 (64.4 mg/L) and for C10 (10.62 mg/L) can be found. Also for C10-C16 the value (<0.06 mg/L) is much closer to the lower value for C16 (0.004 mg/L) than to the C10 value of 10.62 mg/L, or C12 value of ca. 7.8 mg/L. It is generally concluded and experimentally confirmed that all UVCBs in the category are characterized with low water solubility (<1 mg/L).

b) Environmental fate and ecotoxicological properties:

The members of the SCAE Me category are readily biodegradable and show low bioaccumulation potential in biota. Hydrolysis is not a relevant degradation pathway for these substances, due to their ready biodegradability and estimated half-lives in water > 1 year at pH 7 and 8 (HYDROWIN v2.00). The majority of the SCAE Me category members have log Koc values > 3, indicating potential for adsorption to solid organic particles. Therefore, the main compartments for environmental distribution of these substances are expected to be soil and sediment, with the exception of methyl hexanoate (CAS 106-70-7) and methyl octanoate (CAS 111-11-5), for which log Koc < 3 are reported. Therefore, these two substances will be most likely available in the water phase. Nevertheless, all substances are readily biodegradable, indicating that persistency in the environment is not expected. The vapour pressure values of methyl hexanoate and methyl octanoate (> 10 Pa) indicate potential for volatilization of these substances into air. But if released into the atmosphere both these substances are susceptible to indirect photodegradation, with half-lives of 81.6 h and 51 h, respectively (AOPWIN v1.92). This degradation pathway is not relevant for all other category members, since their vapour pressure values are low (0.0001 Pa-4.93 Pa) and no significant release into the atmosphere is expected. Regarding the aquatic toxicity profile in the category, the LC50 values reported show that fish species are the least sensitive aquatic organisms when exposed to the SCAE Me category members. On the other hand, aquatic invertebrates and algae showed the highest sensitivity to these substances. A trend in the toxicity of the monoconstituent substances of the SCAE Me category to aquatic invertebrates and algae is observed, related to the toxicity mode of action (narcosis). The toxicity increases at increasing fatty acid C-chain length (starting from C6 (CAS 106-70-7)) up to a toxicity peak at C12 (for which L(E)C50s and NOECs < 1 mg/L have been reported). With decreasing water solubility at longer C-chain lengths (C14), no toxicity up to the highest attainable concentration is observed in Daphnia and algae. Based on the available data, no toxicity to aquatic microorganisms and terrestrial organisms is to be expected for the substances of the SCAE Me category.

c) Toxicological properties:

The toxicological properties indicate that all the category members show similar toxicokinetic behaviour. The ester bond will be hydrolysed in the gastrointestinal tract before absorption and the breakdown products will be metabolised. Based on the available data, none of the category members caused acute oral, dermal or inhalation toxicity, or skin or eye irritation, or skin sensitisation. No treatment-related effects were noted up to and including the limit dose of 1000 mg/kg bw/day after repeated oral exposure, indicating that the category members have a very limited potential for toxicity. The substances did not show a potential for toxicity to reproduction, fertility and development. No mutagenic or clastogenic potential was observed.

 

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13).

Table 1. Environmental fate parameters of the SCAE Me category

CAS

Phototransformation in air [DT50, 24 h day]

Hydrolysis [DT50, pH 7]

Biodegradation: screening tests

BCF / BAF [L/kg]

Adsorption / Desorption [log Koc]

106-70-7 (a)

(Q)SAR: 81.6 h

(Q)SAR: >1 yr

RA: CAS 111-82-0

Data waiving

(Q)SAR:

log Koc: 1.5 -2.1

111-11-5

(Q)SAR: 51 h

(Q)SAR: >1 yr

RA: CAS 111-82-0

(Q)SAR:

34.5/34.5 (Arnot-Gobas)

(Q)SAR:

log Koc: 2.1 -2.7

110-42-9

(Q)SAR: 37.1 h

(Q)SAR: >1 yr

RA: CAS 111-82-0

(Q)SAR:

82.4/82.4 (Arnot-Gobas)

(Q)SAR:

log Koc: 2.6-3.3

111-82-0

(Q)SAR: 29.2 h

(Q)SAR: >1 yr

Experimental result:
readily biodegradable

(Q)SAR:

154.3/154 (Arnot-Gobas)

(Q)SAR:

log Koc: 3.1-3.8

124-10-7 (b)

--

--

RA: CAS 112-39-0

--

--

112-39-0

(Q)SAR: 20.4 h

(Q)SAR: >1 yr

Experimental result:
readily biodegradable

(Q)SAR:

95.6/238.5 (Arnot-Gobas)

(Q)SAR:
log Koc: 4.1-4.9

112-62-9

--

--

Experimental result:
readily biodegradable

--

--

112-61-8

--

--

RA: CAS 67762-38-3

--

--

85566-26-3

(Q)SAR: 37.1-51 h

(Q)SAR: >1 yr

Experimental result: readily biodegradable

(Q)SAR:
34.5-82.4/34.5-82.4 (Arnot-Gobas)

(Q)SAR:
log Koc: 2.1-3.3

61788-59-8

--

--

Experimental result:  readily biodegradable

--

--

308065-15-8

(Q)SAR: 24-29.2 h

(Q)SAR: >1 yr

RA: CAS 111-82-0
RA: CAS 61788-59-8

(Q)SAR:
154-201/154.3-215.1 (Arnot-Gobas)

(Q)SAR:

log Koc: 3.1-4.4

1234694-02-0

(Q)SAR: 4.7-29.2 h

(Q)SAR: >1 yr

RA: CAS 111-82-0
RA: CAS 112-39-0
RA: CAS 112-62-9

(Q)SAR:
95.6-154/154.3-500.6


(Q)SAR
log Koc: 3.1-4.7

67762-38-3

--

--

Experimental result:
readily biodegradable

--

--

85586-21-6


(Q)SAR: 17.7-20.4 h

--

RA: CAS 67762-38-3

(Q)SAR:
23.3-96.6/238.5-280.9


(Q)SAR:
log Koc: 4.1-5.5

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for these substances a full set of experimental results and/or read-across is given.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

Several experimental biodegradation screening studies confirmed that the members of the SCAE Methyl Esters (Me) category are readily biodegradable according to OECD criteria (75-90.4% biodegradation in 28 days). Due to their ready biodegradability, hydrolysis is not expected to be a relevant degradation pathway for these substances. This information is supported by the available estimated half-lives in water ranging from 3.3 to 7.3 years (pH 7) and 121 to 266 days (pH 8)(HYDROWIN v2.00).

The water solubility values decrease as the fatty acid C-chain length of the SCAE Me substances increases. The most soluble substance is methyl hexanoate (C6, WS 1330 mg/L), followed by methyl octanoate (C8, WS 64.4 mg/L), methyl decanoate (C10, WS 10.6 mg/L) and methyl laurate (C12, WS 7.7 mg/L). At fatty acid C-chain lengths ≥ C14, poor solubility in the water phase is observed with water solubility values of 0.05 mg/L (C14, methyl myristate), 0.004 mg/L (C16, methyl palmitate) and 0.0003 mg/L (C18, methyl stearate). The UVCB substances are also poorly soluble in water: Fatty acids, C16-18, methyl esters (WS < 1 mg/L), Fatty acids, C12-14 (even numbered), methyl esters (WS < 0.06 mg/L) and Fatty acids, C12-16 (even numbered) and C18-unstd., methyl esters (WS < 1 mg/L).

Log Koc values within the category increase at increasing fatty acid C-chain length. Methyl hexanoate (C6) and methyl octanoate (C8) have log Koc values of 1.5-2.1 and 2.1-2.7 (KOCWIN v2.00), respectively. Therefore, both substances are expected to show low adsorption potential to solid organic particles. All other category members have log Koc values > 3, indicating high adsorption potential. Log Koc values increase from 2.6-3.3 for methyl decanoate (C10) up to 4.7-5.5 for methyl stearate (C18). Estimations for the UVCB substances were made based on representative fatty acid components, being the log Koc values 3.1-4.4 for Fatty acids, C2-14, (even numbered), methyl esters; 3.5-4.9 for Fatty acids, C16-18, methyl esters and 3.1-4.7 for Fatty acids, C12-16 (even numbered) and C18-unstd., methyl esters.

The volatilization potential of the SCAE Me category members seems to have an inverse relationship with their fatty acid C-chain length (decreasing values at increasing C-chain length). Methyl hexanoate (C6) and methyl octanoate (C8) show potential for volatilization based on vapour pressure values of 496 and 71.9 Pa, and Henryˈs Law Constants of 37.5 and 79.3 Pa m3/mol. At longer chain lengths, volatilization is not relevant based on vapour pressure values ranging from 4.93 Pa for methyl decanoate (C10) to 0.00181 Pa for methyl stearate (C18). The UVCB substances (Fatty acids, C16-18, methyl esters, Fatty acids, C12-14 (even numbered), methyl esters and Fatty acids, C12-16 (even numbered) and C18-unstd., methyl esters) reported vapour pressure values ranging from < 0.008 Pa to ≤ 0.96 Pa. Therefore, evaporation into air and transport of the SCAE Me substances through the atmospheric compartment is not expected, with the exception of methyl hexanoate (C6) and methyl octanoate (C8). Nevertheless, if released into the air, methyl hexanoate and methyl octanoate are susceptible to indirect photodegradation by OH radicals based on estimated half-lives in air (DT50 values) of 51 and 81.6 hours (for methyl octanoate and methyl hexanoate, respectively)(AOPWIN v1.92).

Based on the information above, once released into the environment, the majority of the SCAE Me category members will be mainly distributed into the soil and sediment compartments due to high adsorption to solid particles and low volatilization potential (vapour pressure < 10 Pa). On the other hand, methyl hexanoate and methyl octanoate will be mainly distributed in the water phase, from which partial volatilization into air can be expected. Nevertheless, since all the substances in the SCAE Me category are readily biodegradable and susceptible to indirect photodegradation in air, persistence in the environment is not expected.

Due to the rapid environmental biodegradation and metabolization via enzymatic hydrolysis of the SCAE Me category members, a relevant uptake and bioaccumulation in aquatic organisms is not expected. Enzymatic breakdown will initially lead to the free fatty acid and methanol (Fukami and Yokoi, 2012). From literature it is well known, that these hydrolysis products will be metabolized and excreted in fish effectively (Cowan-Elsberry et al., 2008; Rodger and Stalling, 1972; Barron et al., 1989; Barron et al., 1990; Murphy & Lutenske, 1990). This is supported by calculated BCF values well below 2000 L/kg (BCFBAF v3.01, Arnot-Gobas, including biotransformation, upper trophic). Please refer to IUCLID Section 5.3.1 for a detailed overview on bioaccumulation of the SCAE Me category members.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.