Registration Dossier

Environmental fate & pathways

Endpoint summary

Administrative data

Description of key information

Additional information

Justification for grouping of substances and read-across

The Glycol ester category covers esters of an aliphatic diol (ethylene glycol (EG), propylene glycol (PG) or 1,3-butyleneglycol (1,3-BG)) and one or two carboxylic fatty acid chains. The fatty acid chains comprise carbon chain lengths ranging from C6 to C18, mainly saturated but also mono unsaturated C16 and C18, branched C18 and epoxidized C18. Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. ethylene glycol) with an organic acid (e.g. stearic acid) in the presence of an acid catalyst (Radzi et al., 2005). The esterification reaction is started by a transfer of a proton from the acid catalyst to the acid to form an alkyloxonium ion. The acid is protonated on its carbonyl oxygen followed by a nucleophilic addition of a molecule of the alcohol to a carbonyl carbon of acid. An intermediate product is formed. This intermediate product loses a water molecule and a proton to give an ester (Liu et al, 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Di- and/or monoesters are the final products of esterification of an aliphatic diol and fatty acids.

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, 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 Glycol esters.

CAS

EC name

Molecular weight

Carbon number in Acid

Carbon number in dihydroxy alcohol

Total Carbons in Glycol Esters

CAS 111-60-4 (b)

Glycol stearate

MW 328.53

C18

C2

C20

CAS 624-03-3 (a)          

Ethane-1,2-diyl palmitate

MW 538.89

C16

C2

C34

CAS 627-83-8               

Ethylene distearate

MW 563.0

C18

C2

C38

CAS 91031-31-1

Fatty acids, C16-18, esters with ethylene glycol

MW 300.48 - 563.00

C16-18

C2

C18-38

CAS 151661-88-0

Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol

MW 328.54 - 622.97

C18

C2

C20-38

CAS 29059-24-3

Myristic acid, monoester with propane-1,2-diol

MW 286.45

C14

C3

C17

CAS 1323-39-3

Stearic acid, monoester with propane-1,2-diol

MW 342.55

C18

C3

C21

CAS 37321-62-3

Dodecanoic acid, ester with 1,2-propanediol

MW 258.40 - 440.71

C12

C3

C15-27

CAS 68958-54-3

1-methyl-1,2-ethanediyl diisooctadecanoate

MW 609.03

C18

C3

C39

CAS 31565-12-5

Octanoic acid ester with 1,2-propanediol, mono- and di-

MW 202.29 - 328.49

C8

C3

C11-19

CAS 85883-73-4

Fatty acids, C6-12, esters with propylene glycol

MW 202.29 - 440.71

C6-12

C3

C9-27

CAS 68583-51-7

Decanoic acid, mixed diesters with octanoic acid and propylene glycol

MW 328.49 - 384.59

C8-10

C3

C19-23

CAS 84988-75-0

Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol

MW 286.46 - 609.02

C14-18

C3

C17-39

CAS 853947-59-8

Butylene glycol dicaprylate / dicaprate

MW 342.52 - 398.63

C8-10

C4

C20-24

(a) Category members subject to registration are indicated in bold font.

(b) Substances not subject to registration are indicated in normal font.

 

Grouping of substances into this category is based on:

 

(1) common functional groups: the substances of the category are characterized by ester bond(s) between an aliphatic diol (ethylene glycol (EG), propylene glycol (PG) or 1,3-butyleneglycol (1,3-BG)) and one or two carboxylic fatty acid chains. The fatty acid chains comprise carbon chain lengths ranging from C6 to C18, mainly saturated but also mono unsaturated C16 and C18, branched C18 and epoxidized C18, are included into the category; and

 

(2) common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals: glycol esters are expected to be initially metabolized via enzymatic hydrolysis in the corresponding free fatty acids and the free glycol alcohols such as ethylene glycol and propylene glycol. The hydrolysis represents the first chemical step in the absorption, distribution, metabolism and excretion (ADME) pathways expected to be similarly followed by all glycol esters. The hydrolysis is catalyzed by classes of enzymes known as carboxylesterases or esterases (Heymann, 1980). Ethylene and propylene glycol are rapidly absorbed from the gastrointestinal tract and subsequently undergo rapid biotransformation in liver and kidney (ATSDR, 1997; ICPS, 2001; WHO, 2002; ATSDR, 2010). Propylene glycol will be further metabolized in liver by alcohol dehydrogenase to lactic acid and pyruvic acid which are endogenous substances naturally occurring in mammals (Miller & Bazzano, 1965, Ritchie, 1927). Ethylene glycol is first metabolised by alcohol dehydrogenase to glycoaldehyde, which is then further oxidized successively to glycolic acid, glyoxylic acid, oxalic acids by mitochondrial aldehyde dehydrogenase and cytosolic aldehyde oxidase (ATSDR, 2010; WHO, 2002). The anabolism of fatty acids occurs in the cytosol, where fatty acids esterified into cellular lipids that are the most important storage form of fatty acids (Stryer, 1994). The catabolism of fatty acids occurs in the cellular organelles, mitochondria and peroxisomes via a completely different set of enzymes. The process is termed ß-oxidation and involves the sequential cleavage of two-carbon units, released as acetyl-CoA through a cyclic series of reaction catalyzed by several distinct enzyme activities rather than a multienzyme complex (Tocher, 2003); and

 

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

(a) Physico-chemical properties: Due to their structural similarities, the members of the Glycol Esters Category show a trend in their physico-chemical properties. The molecular weight of the category members increases with increasing C-chain lengths from 202.29 to 622.97. They are characterized by low water solubility (< 0.05 mg/L), high log Kow (> 5), high increasing (based on C-chain lengths) log Koc (3.2 - 9.1) and low vapour pressure (VP: < 0.001 Pa); and

 

(b) Environmental fate and ecotoxicological properties: Considering the low water solubility and the potential for adsorption to organic soil and sediment particles, the main compartment for environmental distribution is expected to be the soil and sediment. Nevertheless, persistency in these compartments is not expected since the members of the Glycol Esters Category are readily biodegradable. Evaporation into air and the transport through the atmospheric compartment is not expected since the category members are not volatile based on the low vapour pressure. All members of the category are readily biodegradable and did not show any effects on aquatic organisms in acute and chronic tests representing the category members up to the limit of water solubility. Moreover, bioaccumulation is assumed to be low based on available metabolism data.

(c) Toxicological properties: The toxicological properties show that all category members have a similar toxicokinetic behaviour (hydrolysis of the ester bond before absorption followed by absorption and metabolism of the breakdown products) and that the constant pattern consists in a lack of potency change of properties across the category, explained by the common metabolic fate of glycol esters independently of the fatty acid chain length and degree of glycol substitution. Thus, no category member showed acute oral, dermal or inhalative toxicity, no skin or eye irritation properties, no skin sensitisation, are of low toxicity after repeated oral exposure and are not mutagenic or clastogenic and have shown no indications for reproduction toxicity and have no effect on intrauterine development.

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 and 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).

 

The environmental fate parameters of the Glycol Esters Category members are presented in the following table:

CAS

Phototransformation in air [DT50, 24 h day]

Hydrolysis [DT50, pH 7]

Biodegradation: screening tests

BCF/BAF [L/kg]

Adsorption [log Koc]

624-03-3 (a)

 

9.4 h

> 1 yr

RA: CAS 627-83-8

RA: CAS 91031-31-1

0.8932/0.958 (Arnot-Gobas)

7.8 (MCI)

627-83-8

8.3 h

> 1 yr

readily biodegradable

0.893/0.9042 (Arnot-Gobas)

8.8 (MCI)

91031-31-1 (b)

 

8.8 - 15.6 h

> 1 yr

readily biodegradable

2.717 - 25.74/3.44 - 25.8 (Arnot-Gobas)

3.4 - 8.3 (MCI)

68958-54-3

--

--

readily biodegradable

--

--

68583-51-7

14.7 - 19.8 h

> 1 yr

readily biodegradable

2.717 - 25.74/3.44 - 25.8 (Arnot-Gobas)

3.8 - 4.8 (MCI)

84988-75-0

2.5 - 10.5 h

> 1 yr

RA: CAS 68958-54-3

0.8993 - 1.05/0.893 - 0.8954 (Arnot-Gobas)

7.0 - 9.1 (MCI)

853947-59-8

 

--

--

readily biodegradable

--

--

(a) Category members subject to registration are indicated in bold font.

(b) Substances not subject to registration are indicated in normal font.

Lack of data for a given endpoint is indicated by “--“.

 

Several experimental studies confirmed that all members of the Glycol Esters Category are readily biodegradable according to the OECD criteria (61 - 82% biodegradation after 28 d). Therefore, the category members will not be persistent in the environment. The degradation via abiotic hydrolysis is not considered to be a relevant degradation pathway in the environment since QSAR results using HYDROWIN v2.00 resulted in DT50 > 1 yr at pH 7.

Considering the low water solubility (< 0.05 mg/L) and the potential for adsorption to organic soil and sediment particles (log Koc: 3.2 - 9.1, MCI method, KOCWIN v2.00), the main compartment for environmental distribution is expected to be the soil and sediment. Nevertheless, persistency in these compartments is not expected since the members of the Glycol Esters Category are readily biodegradable. Evaporation into air and the transport through the atmospheric compartment is not expected since the category members are not volatile based on the low vapour pressure (VP: < 0.001 Pa (SPARC v4.5); Nagel, 2011). Accumulation in air and the subsequent transport to other environmental compartments is not anticipated. However, if released into air, all category members are susceptible to indirect photodegradation by OH-radicals with a DT50: < 24 h (AOPWIN v1.92).

Due to the low water solubility, rapid environmental biodegradation and metabolisation via enzymatic hydrolysis of the Glycol Esters category members, a relevant uptake and bioaccumulation in aquatic organisms is not expected. Enzymatic breakdown will initially lead to the free fatty acid and the free glycol alcohol (e. g. ethylene glycol). From literature it is well known, that these hydrolysis products will be metabolised and excreted in fish effectively (Heymann, 1980; Lech & Bend, 1980; Lech & Melancon, 1980; Murphy & Lutenske, 1990). This is supported by low calculated BCF values of 0.893 - 41.86 L/kg ww (BCFBAF v3.01, Arnot-Gobas, including biotransformation, upper trophic). Please refer to IUCLID Section 5.3 for a detailed overview on bioaccumulation of the Glycol Esters Category members.

 

References

Agency for Toxic Substances and Disease Registry (ATSDR) (1997): Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.

 

Agency for Toxic Substances and Disease Registry (ATSDR) (2010): Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.

 

Gubicza, L., Kabiri-Badr, A., Keoves, E., Belafi-Bako, K. (2000): Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

 

Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby, W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication, 2nd Ed., New York: Academic Press, pp. 291-323.

 

International Programme on Chemical Safety (IPCS) (2001): Ethylene Glycol. Poisons Information Monograph. PIM 227.

 

Lech, J.J. & Bend, J.R. (1980): Relationship between biotransformation and the toxicity and fate of xenobiotix chemicals in fish. Environ. Health Perspec. 34, 115-131.

 

Lech, J., Melancon, M. (1980): Uptake, metabolism, and deposition of xenobiotic chemicals in fish. EPA-600 3-80-082. U.S. Environmental Protection Agency, Duluth, MN, USA.

 

Lilja, J., Wärna, J., Salmi, T., Petterson, L.J., Ahlkvist, J., Grénman, H., Rönneholm, M., Murzin, D.Y. (2005): Esterification of propanoic acid with ethanol, 1-propanol and butanol over a heterogeneous fiber catalyst. Chemical Engineering Journal, 115(1-2): 1-12.

 

Liu, Y., Lotero, E., Goodwin, J.G. Jr. (2006): A comparison of the esterification of acetic acid with methanol using heterogeneous versus homogeneous acid catalysis. Journal of Catalysis, 242 (2): 278-286.

 

Miller, O.N., Bazzano, G. (1965): Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119, 957-973.

 

Murphy, P.G., Lutenske, N.E. (1990): Bioconcentration of haloxyfop-methyl in bluegill (Lepomis macrochirus Rafinesque). Environ. Intern. 16, 219-230.

 

Radzi, S.M., Basri, M., Salleh, A.B., Ariff, A., Mohammed, R., Rahman, M.B.A., Rahman, R.N.Z.R.A. (2005): High performance enzymatic synthesis of oleyl oleate using immobilised lipase from Candida antartica. Electronic Journal of Biotechnology 8: 292-298.

 

Ritchie, A.D. (1927): Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4, 327-332.

 

Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg; Berlin; Oxford: Spektrum Akad. Verlag.

 

Tocher, D.R. (2003): Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish. Reviews in Fisheries Science 11(2), 107-184.

 

WHO (2002): Ethylene Glycol: Human Health Aspects. Concise International Chemical Assessment Document 45.

 

Zhao, Z. (2000). Synthesis of butyl propionate using novel aluminophosphate molecular sieve as catalyst. Journal of Molecular Catalysis 154(1-2): 131-135.