Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: not irritating (OECD 404)
Eye irritation: not irritating (OECD 405)

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

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: 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).

Skin and Eye Irritation

Data Matrix

CAS #

111-60-4 (b)

624-03-3 (a)

627-83-8

91031-31-1

151661-88-0

68583-51-7

84988-75-0

Skin irritation

Not irritating

RA: CAS 91031-31-1

RA: CAS 627-83-8

RA: CAS 68583-51-7

Not irritating

Not irritating

Not irritating

Not irritating

RA: CAS 91031-31-1

RA: CAS 627-83-8

RA: CAS 68583-51-7

Eye irritation

--

RA: CAS 627-83-8

Not irritating

RA: CAS 627-83-8

--

Not irritating

Not irritating

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

(b) Substances not subject to registration are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

Skin irritation

CAS 627-83-8

The skin irritation properties of ethylene distearate have been investigated in several studies (CAS 627-83-8).

The skin irritation properties of ethylene distearate were tested in a study equivalent to OECD guideline 404 (Wnorowski, 1991a). In the study, 3 male and 3 female New Zealand White rabbits were exposed to 0.5 g of the unchanged test substance, applied to the shaved and abraded skin for 25 h using an occlusive dressing. The treated skin was observed and evaluated at 25 and 72 h post-application. No erythema or edema was observed in any animal during the study period on intact shaved skin. On abraded skin, slight erythema in 2 animals was observed at 25 h, being fully reversible within 72 h. No further local or systemic effects were apparent in any animal during the study period.

In an equivalently conducted study from the same laboratory (Wnorowski, 1991b), the results of the above discussed study were confirmed. No erythema and no edema formation were observed in the test animals on intact skin and erythema on abraded skin was fully reversible within 72 h. No other local or systemic effects were described.

Additionally, the skin irritating properties of ethylene distearate were tested similarly to OECD guideline 404 in New Zealand rabbits and according to Draize type procedures with no further details in rabbits (Bouffecoux, 1995; Elder, 1982). The test animals showed no reactions on skin during the study period and no other local or systemic effects were reported (Bouffecoux, 1995). In the studies with Draize type procedures, no effects on skin or slight skin reactions were described. According to the author, the test substance was therefore found to be non-irritating to slightly irritating.

In summary, ethylene distearate is not irritating to the skin.

 

CAS 68583-51-7

Several animal studies and one human patch test investigating the skin irritation properties of Decanoic acid mixed diesters with octanoic acid and propylene glycol are available.

The skin irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD guideline 404 in compliance with GLP (Guest, 1989). In the study, 3 New Zealand White rabbits were exposed to 0.5 mL of the undiluted test substance, applied to the shaved skin for 4 h using a semiocclusive dressing. The treated skin was observed and evaluated at 1, 24, 48 and 72 h post-application. In 1/3 animals 24 h after removal of the test substance, slight erythema was observed which was fully reversible within 48 h (mean erythema score 0.3 after 24-72 h). The remaining animals revealed no erythema formation. No edema formation (mean over 24, 48 and 72 h) or further local or systemic effects were apparent in any animal during the study period.

Four further studies are available, in which the skin irritating properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were studied in rabbits (Guest, 1988; Kästner, 1988; Masson, 1985; Consultox Laboratories Ltd., 1972).

In each study, 3-6 rabbits were exposed to 0.5 mL of the undiluted test material, applied to the shaved or abraded skin for 4 h or 24 h using a semi-occlusive or occlusive dressing. The treated skin was observed for reactions after patch removal and evaluations were made at 1, 24 and 72 h or at 1, 24, 48 and 72 h post-application.

In the first study, slight erythema with a mean erythema score of 0.2 over 24, 48 and 72 h out of all 3 animals were observed with all effects being fully reversible within 48 h. No edema formation was observed during the study period in any animal (Guest, 1988). In the second study, the observed skin reaction consisted of slight to well defined erythema with a mean erythema score of 1.25 over 24, 48 and 72 h out of all 4 animals. All skin redness was fully reversible within 7 days. Slight edema formation was apparent with a mean edema score of 0.55 over 24, 48 and 72 h out of all 4 animals being fully reversible within 7 days (Kästner, 1988).In the third study, slight erythema was observed with a mean erythema score of 0.44 over 24, 48 and 72 h out of all 6 animals. The erythema formation in 3/6 animals was not fully reversible within the observation period of 72 h. No edema formation was observed during the study period in any animal (Masson, 1985). In the fourth study, no skin reactions and no further local or systemic effects were observed during the study period in any animal (Consultox Laboratories Ltd., 1971).

Furthermore, one human patch test is available investigating the skin irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol after a single dermal application (Christophers, 1976).

The human patch test with the test substance was performed on 120 volunteers under occlusive conditions. The undiluted test material was applied to the back of the test subjects under occlusive conditions. After 24 h the test plaster was removed and skin reactions were observed 24, 48 and 72 h after application. No clinical signs and no skin reaction were observed in any volunteer during the study period.

Thus, good skin compatibility of the test substance was observed in the study.

 

In summary, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is not skin irritating to the skin.

 

CAS 84988-75-0 and CAS 624-03-3

No studies are available investigating the skin irritating properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol (CAS 84988-75-0) and ethane-1,2-diyl palmitate (CAS 624-03-3). In order to fulfil the standard information requirements set out in Annex VII, 8.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category members ethylene distearate (CAS 627-83-8) and Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) and Fatty acids, C16-18, esters with ethylene glycol (CAS 91031-31-1) was conducted.

The studies from the category members ethylene distearate and Decanoic acid, mixed diesters with octanoic acid and propylene glycol are described under the respective CAS numbers.

Fatty acids, C16-18, esters with ethylene glycol was tested in a study according to OECD guideline 404 in compliance with GLP (Coguet, 1976). In the study, 6 New Zealand White male rabbits were exposed to 0.5 mL of the test substance in olive oil, applied to the shaved and abraded skin for 24 h using an occlusive dressing. The treated skin was observed and evaluated at 24 and 72 h post-application. On intact skin, 2/6 animals showed slight erythema (on abraded skin 5/6 showed slight irritating effects) after 24 h which were fully reversible within 72 h (mean erythema score over 24 and 72 h out of all 6 animals = 0.22). No edema formation or further local or systemic effects were apparent in any animal during the study period. In summary, no skin irritating properties of the category members were apparent, therefore interpolation to Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol and ethane-1,2-diyl palmitate, does not assume any skin irritating properties.

 

Additional data

In addition to the above discussed studies, two skin irritation studies of the category members Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene (CAS 151661-88-0) and Glycol Stearate (CAS 111-60-4) are available, showing no skin irritation, as well.

 

Conclusion of skin irritation properties

In conclusion, the skin irritation properties of several Glycol Ester category members have been investigated in vivo indicating no or low skin irritating properties. Therefore, none of the category members of the Glycol Ester group is skin irritating.

 

Eye irritation

CAS 627-83-8

Several studies investigating the eye irritation properties of ethylene distearate are available.

The eye irritation properties of ethylene distearate were tested in a study similarly performed to OECD guideline 405 (Wnorowski, 1991a). In a group of 6 New Zealand white rabbits, 0.1 g of the test substance was applied into the eye. Observation of the eyes was performed 24, 48 and 72 h after application. No effects on cornea and iris were noted in any animal during the study period. However, mild conjunctival redness was observed in 4/6 animals after 24 h and in 2/6 animals moderate redness was apparent. In 2 animals the mild redness was still persistent after 72 h with a mean score of 0.78 over 24, 48 and 72 h out of all 6 animals. Chemosis was observed in 1/6 animals after 24 h being fully reversible within 48 h. No chemosis was observed in the remaining 5 animals during the study period. No further systemic effects or abnormal behaviour were observed in any animal during the study period.

An additional study of the same laboratory with ethylene distearate similarly to OECD guideline 405 was conducted (Wnorowski, 1991b). No effects on cornea and iris were apparent in any animal during the study period and no chemosis was observed in the test animals. Mild to moderate conjunctival redness was observed in all animals being fully reversible within 72 h post-instillation with a mean score of 0.61 over 24, 48 and 72 h out of all 6 animals. No further local or systemic signs of toxicity were apparent in the test animals.

Further studies are available investigating the eye irritating properties of ethylene distearate in rabbits according to OECD guideline 405 or according to Draize type procedures without further details (Bouffechoux, 1995; Elder 1982). According to the author, the test substance was practically non-irritating or not an irritant in the test animals using the Draize type procedure (Elder, 1982). In the study by Bouffecoux (1995), no effects on cornea and iris were apparent and conjunctival redness was observed in all animals being fully reversible within 72 h with a mean score of 0.8 over 24, 48 and 72 h out of all animals. No further local or systemic effects were reported.

In summary, ethylene distearate is not eye irritating.

 

CAS 68583-51-7

Several studies investigating the eye irritation properties of Decanoic acid mixed diesters with octanoic acid and propylene glycol are available.

The eye irritation properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD guideline 405 in compliance with GLP (Kästner, 1988).

In a group of 4 male rabbits (Kleinrusse), 0.1 mL of the undiluted test substance was applied into one eye, in a single application without washing. The eyes were observed and reactions were evaluated 1, 6, 24, 48 and 72 h after application. No effects on corneal opacity and iris were noted at any time point in any animal. However, mild conjunctival redness was observed in 2/4 animals at the 1 h reading time point. In one of these animals the effect was fully reversible within 6 h; in the second animal mild redness was apparent until 6 h after application being fully reversible after 24 h as well (mean score over 24, 48 and 72 h out of all 4 animals = 0). No chemosis or exudation were observed during the study period in any animal.No further local or systemic effects were observed in any animal during the study period.

Three further studies are available, in which the eye irritating properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol were studied in rabbits (Consultox Laboratories Ltd., 1976; Guest, 1988; Guest, 1989).

In each study, 0.1 mL of the undiluted test material was instilled in one single application into the eye of 3 or 6 rabbits. Reactions in the eyes were observed at 1, 24, 48 and 72 h (Guest 1988 and 1989) and additionally at Day 4 and Day 7 after application (Consultox Laboratories Ltd., 1976).

In one study, the treated eyes of 2 groups with each 3 animals (washed eyes and unwashed eyes) were observed. In both groups, no effects on cornea, iris, chemosis and discharge were observed. In the group without washing, 1/3 animals showed slight redness and in 1/3 animals moderate erythema of the conjunctivae was observed, which were fully reversible within 48 h (Consultox Laboratories Ltd., 1976).

In both studies by Guest (1988 and 1989), no effects on cornea, iris, chemosis and discharge and no other local or systemic effects were apparent after 24, 48 and 72 h. In addition, no effects on conjunctivae were observed in the study by Guest, 1988. In the second study (Guest, 1989), after 1 h, mild redness was observed in 1/3 animals and moderate redness in 2/3 animals. After 24 h minimal redness was observed in 3/3 animals and was fully reversible within 48 h in all animals with a mean score of 0.3 over 24, 48 and 72 h out of all 3 animals.

In summary, Decanoic acid, mixed diesters with octanoic acid and propylene glycol is not eye irritating.

 

CAS 84988-75-0

One study investigating the eye irritation properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol is available.

In the study, Decanoic acid, mixed diesters with octanoic acid and propylene glycol were tested in a study according to OECD guideline 405 in compliance with GLP (Steiling, 1991).

In a group of 3 male rabbits (Kleinrusse), 0.1 mL of the undiluted test substance was applied into one eye, in a single application without washing. The eyes were observed and reactions were evaluated 1, 24, 48 and 72 h after application. No effects on cornea and iris were noted at any time point in any animal. However, slight erythema was observed in 2/3 animals at the 24 h reading time point being fully reversible within 48 h (mean score over 24, 48 and 72 h out of all 3 animals = 0.22). Slight chemosis was observed in 1 animal until the 24 h reading time point. No further local or systemic effects were observed in any animal during the study period.

In summary, Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol is not eye irritating.

 

CAS 624-03-3

No studies are available investigating the eye irritating properties of ethane-1,2-diyl palmitate.In order to fulfil the standard information requirements set out in Annex VII, 8.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category ethylene distearate (CAS 627-83-8) was conducted.

The available data from the category member ethylene distearate is described under the respective CAS number.

Based on the available data on eye irritation properties of the category member ethylene distearate, it was concluded, that there is no evidence of eye irritation properties of ethane-1,2-diyl palmitate.

 

Conclusion for eye irritation properties

In conclusion, the eye irritation properties of the Glycol Ester category members have been investigated in 11 in vivo studies indicating no eye irritation properties. Therefore, none of the category members of the Glycol Ester group is eye irritating.

 

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.Gubicza, L. et al. (2000). Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

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

Lilja, J. et al. (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. et al. (2006). A comparison of the esterification of acetic acid with methanol using heterogeneous versus homogeneous acid catalysis. Journal of Catalysis 242: 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.

Radzi, S.M. et al. (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. 


Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the Glycol Ester Category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on Irritation / Corrosion do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.