Registration Dossier

Ecotoxicological information

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 alcohol 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

 CAS 4219 -49 -2  2 -hydroxyethyl palmitate  MW 300.48 - 538.89  C16  C2  C18 -34

(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: The physico-chemical properties of the category members are similar or follow a regular pattern over the category. The pattern observed depends on the fatty acid chain length and the degree of esterification (mono- or diesters). The molecular weight of the category members ranges from 202.29 to 622.97 g/mol. The physical appearance is related to the chain length of the fatty acid moiety, the degree of saturation and the number of ester bonds. Thus, mono- and diesters of short-chain fatty acids and unsaturated fatty acids (C6-14 and C16:1, C18:1) as well as diesters of branched fatty acids (C18iso) are liquid, while mono- and diesters of long-chain fatty acids are waxy solids. All category members are non-volatile (vapour pressure: ≤ 0.066 Pa). The octanol/water partition coefficient increases with increasing fatty acid chain length and number of ester bonds, ranging from log Kow = 1.78 (C6 PG monoester component) to log Kow >10 (C12 PG diester component). The water solubility decreases accordingly (624.3 mg/L for C6 PG monoester component to >0.01 mg/L for C18 PG diester component); 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 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 ecotoxicological parameters for the terrestrial compartment of the Glycol Esters Category are presented in the following table.

 

Ecotoxicological parameters for the aquatic toxicity of the Glycol Esters Category

CAS

Short-term toxicity to fish

Long-term toxicity to fish

Short-term toxicity to aquatic invertebrates

Long-term toxicity to aquatic invertebrates

Toxicity to aquatic algae

Toxicity to microorganisms

624-03-3 (a)

 

RA: CAS 627-83-8

RA: CAS 68958-54-3

Waiving based on CSA

RA: CAS 68583-51-7

RA: CAS 853947-59-8

RA: CAS 853947-59-8

RA: CAS 91031-31-1

RA: CAS 853947-59-8

RA: CAS 68958-54-3

RA: CAS 853947-59-8

627-83-8

LC50 (96 h) > 0.3 mg/L

Waiving based on CSA

RA: CAS 68583-51-7

RA: CAS 853947-59-8

RA: CAS 853947-59-8

RA: CAS 91031-31-1

RA: CAS 853947-59-8

RA: CAS 68583-51-7

RA: CAS 853947-59-8

91031-31-1 (b)

 

LC50 (96 h) > 10000 mg/L (RL4 study)

 

RA: CAS 68583-51-7

RA: CAS 627-83-8

Waiving based on CSA

RA: CAS 68583-51-7

RA: CAS 853947-59-8

EC50 (48 h) > 100 mg/L

RA: CAS 853947-59-8

 

RA: CAS 68583-51-7

68958-54-3

LC50 (96 h) > 100 mg/L

--

--

--

--

EC10 (16 h) > 10000 mg/L

68583-51-7

LC0 (96 h) > 39 mg/L

Waiving based on CSA

EC50 (48 h) > 2.7 mg/L

 

RA: CAS 853947-59-8

NOEC (72 h) > 5.3 mg/L

EC10 > 0.99 mg/L

84988-75-0

RA: CAS 68958-54-3

RA: CAS 68583-51-7

Waiving based on CSA

RA: CAS 68583-51-7

RA: CAS 853947-59-8

RA: CAS 853947-59-8

RA: CAS 68583-51-7

RA: CAS 853947-59-8

RA: CAS 68958-54-3

RA: CAS 853947-59-8

853947-59-8

LC50 (96 h) > 14 mg/L

--

EC50 (48 h) > 2 mg/L

NOELR (21 d) > water solubility

NOEC (72 h) > 3 mg/L

EC10/50 (3 h) > 1099 mg/L

 4219 -49 -2 RA: CAS 91031 -31 -1

RA: CAS 68583-51-7

RA: CAS 627-83-8

 --  

RA: CAS 68583-51-7

 
  

RA: CAS 853947-59-8

RA: CAS 91031 -31 -1  

RA: CAS 853947-59-8

 

RA: CAS 68583-51-7

 

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

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

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

 

In accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5, grouping and read-across, the Glycol Esters Category members are not considered to be harmful to aquatic organisms based on the results from short-term studies with fish, aquatic invertebrates and algae and long-term results on toxicity to aquatic invertebrates. All category members are structurally similar and read-across was performed to the structurally most similar category member(s). The available studies cover the variability of the category with different alcohol and fatty acid chain lengths. The data gaps within the category were filled by interpolation and if necessary by extrapolation since the category members are characterized by a similar pattern in the ecotoxicological toxicity profile. No trend in toxicity was observed since no effects were recorded up to the limit of water solubility. There is no convincing evidence that any one of the category members might lie out of the overall profile of this category.

 

In particular, short-term studies with freshwater species from all three trophic levels (algae, aquatic invertebrates and fish) are available. Four acute toxicity studies to fish according to internationally accepted guidelines are available for the category members ethylene distearate (CAS 627-83-8), decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and propylene glycol diisostearate (CAS 68958-54-3). No effects were observed up to the limit of water solubility. The available studies are covering the variability of the category with different alcohol components and representative fatty acid chain lengths. Thus, the data gaps can be covered by interpolation.

The same result was found in short-term toxicity studies with aquatic invertebrates for the category members decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and butylene glycol dicaprylate / dicaprate (CAS 853947-59-8). No toxicity was observed up to the limit of water solubility in the available studies. Based on the results from these studies in combination with an available chronic result with Daphnia magna, there is no convincing evidence that the other category members lie out of the overall toxicity profile. Despite the overall low water solubility of the category members (< 0.05 mg/L) the results from decanoic acid, mixed diesters with octanoic acid and propylene glycol and butylene glycol dicaprylate / dicaprate are considered to exhibit a higher bioavailability through the water phase which is the most common route of uptake in standard aquatic tests. The water solubility directly correlates with the hydrocarbon chain lengths of the fatty acid (Lide, 2005). Thus, this read-across can be seen as a worst case.

 

Three standard guideline studies investigating the toxicity to aquatic algae are available for the following substances decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) and butylene glycol dicaprylate / dicaprate (CAS 853947-59-8). No toxicity was observed up to the limit of water solubility in the available studies. The available studies are covering the variability of the category with different alcohol components and fatty acid chain lengths at the lower and upper end of the category.Thus, the data gaps can be covered by interpolation.

 

One long-term study with Daphnia magna is available for the category member butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) resulting in a NOEC (21 d) > water solubility. This study was used as read-across for the other category members based on structural similarities. Moreover, it can be concluded that this substance can be seen as a worst case read-across approach based on the smaller fatty acid chain lengths which probably exhibits a higher water solubility since the hydrocarbon chain lengths of the fatty acid is directly correlated with the water solubility (Lide, 2005).

 

Toxicity to microorganisms was investigated in two studies for decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and butylene glycol dicaprylate / dicaprate (CAS 853947-59-8), respectively. The first study with decanoic acid, mixed diesters with octanoic acid and propylene glycol was not considered to be reliable since only one single species (Pseudomonas putida) was tested. Nevertheless, no effects on O2-consumption were observed. The result from the second study with butylene glycol dicaprylate / dicaprate according to an accepted guideline was considered valid. No effects on respiration of activated sludge microorganisms were observed. Based on structural similarities this study was used for read-across throughout the category. In combination with results from the available biodegradation studies it can be concluded that no effects on the STP microorganism community and the subsequent degradation process in sewage treatment plants is anticipated.

 

In conclusion, no effects on aquatic organisms were observed in the available studies for the Glycol Esters category members in any of the three trophic levels (fish, daphnia, algae) for substances within the category up to the limit of water solubility, neither in the short-term toxicity tests nor in a long-term test with daphnia. The Glycol Esters category is a robust category with a large amount of reliable data which allows a conclusive overview about the overall ecotoxicity profile of all category members. In each case of read-across, the best suited read-across was chosen. Nevertheless, as it can be seen in the data matrix of the category justification in IUCLID Section 13, all reliable data in the category support the hazard assessment of each category member by showing a consistent pattern of results.

 

For a detailed reference list please refer to the CSR or IUCLID section 13.