Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP, category approach)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, category approach)
Acute toxicity: Inhalation LC50 (rat, m/f): > 2.916 mg/L air (OECD 403, category approach)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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).

Acute Toxicity

Data Matrix

CAS

111-60-4 (b)

624-03-3 (a)

627-83-8

151661-88-0

31565-12-5

68583-51-7

853947-59-8

84988-75-0

Acute toxicity oral

LD50 (rat) > 2000 mg/kg bw

RA: CAS 627-83-8

RA: CAS 68583-51-7

LD50 (rat) > 5000 mg/kg bw

LD50 (rat) > 2000 mg/kg bw

--

LD50 (rat) > 2000 mg/kg bw

--

RA: CAS 627-83-3

RA: CAS 68583-51-7

RA: CAS 151661-88-0

Acute toxicity inhalation

--

RA: CAS 68583-51-7

RA: CAS 68583-51-7

--

--

LC50 (rat, guinea pig)> 200 ppm

--

RA: CAS

68583-51-7

Acute toxicity dermal

--

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-12-5

LD50 (rat) > 2000 mg/kg bw

LD50 (rat) > 2000 mg/kg bw

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA from CAS 31565-

LD50 (rat) > 2000 mg/kg bw

RA: CAS 151661-88-0

RA: CAS 853947-59-8

RA: CAS 31565-

(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 “--“.

Acute oral toxicity

CAS 627-83-8

The acute toxicity via the oral route of ethylene distearate has been investigated in rats and mice in several studies (CAS 627-83-8).

A study for acute oral toxicity of ethylene distearate was performed in rats in accordance with OECD guideline 401 (Wnorowski, 1991). A group of 10 Wistar rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance in carboxymethyl cellulose by gavage. The observation period following administration was 14 days. During the study period, no mortality and no clinical signs of toxicity were observed in any animal. All test animals showed normal body weight gain. Therefore, the oral LD50 in male and female rats was greater than 5000 mg/kg bw.

Further studies in which the acute oral toxicity of ethylene distearate was studied in rats and mice similar to OECD guideline 401 are available. The test material was administered by gavage at doses of 5000 or 2000 mg/kg bw (Wnorowski, 1991; Bouffechoux, 1995) and at three doses up to 10000 mg/kg bw (Klusman, 1974). No mortalities were observed and no abnormalities in body weight were recorded during the 14-day observation period in the studies. No signs of toxicity were observed in the studies by Bouffechoux and Klusman (1995, 1991). After dosage of up to 10000 mg/kg bw, slightly decreased motor activity and diarrhoea and proneness were observed in the test groups and gross necropsy of these animals showed moderate congestion of the liver, kidneys and adrenal gland. Tissue observations at all doses were not remarkable (Klusman, 1974).

Furthermore, four independent acute oral toxicity studies in doses up to 16000 mg/kg bw in rats with glycol distearate are reported (Elder, 1982). Doses above 13000 mg/kg bw were noted to produce diarrhoea, wet oily coats and nasal haemorrhage being reversible within 10 days. In one study, at gross necropsy the stomach contained residues which appeared to be the test material.

In summary, the oral LD50 of ethylene distearate is greater than 5000 mg/kg bw.

CAS 68583-51-7

Several studies investigating the acute toxicity via the oral route of Decanoic acid mixed diesters with octanoic acid and propylene glycol are available (CAS 68583-51-7).

A study for acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was performed in rats in accordance with EU Method B.1 under GLP conditions (Potokar, 1988). A group of 10 Wistar rats (5 males and 5 females) was dosed with 2000 mg/kg bw of the test material in peanut oil by gavage. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. No effect on body weight was noted. During necropsy, in 1/5 males a tightly filled urinary bladder and in 1/5 females a mild hydrometra was observed. These findings were not considered to be substance-related. Therefore, under the conditions of this study, the oral LD50 in male and female rats was greater than 2000 mg/kg bw.

Further studies are available, in which the acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was studied in rats and mice according to OECD guideline 401.

In each case, the test material was administered by gavage at a dose of 5000 mg/kg bw or 5 mL/kg bw (Blackwell, 1989; Blackwell, 1988; Consultox Laboratories Ltd., 1972; Masson, 1985). No mortalities were observed during the 14-day study periods. No substance related signs of toxicity were observed in the studies. Moreover, no abnormalities in body weight (gain) were observed during the observation period and macroscopic examinations at termination revealed no treatment-related changes (Blackwell, 1989; Blackwell, 1988).

In summary, the oral LD50 of Decanoic acid mixed diesters with octanoic acid and propylene glycol is greater than 2000 mg/kg bw.

CAS 84988-75-0

No studies are available investigating the acute oral toxicity of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol. In order to fulfil the standard information requirements set out in Annex VII, 8.5, 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), Decanoic acid, mixed diesters with octanoic acid and propylene glycol; CAS 68583-51-7) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was conducted.

In addition to the already discussed studies from the category members ethylene distearate, Decanoic acid, mixed diesters with octanoic acid and propylene glycol (described under the respective CAS numbers), an additional study evaluating the acute oral toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) is available (Potokar, 1989). The study was performed equivalent to OECD guideline 401 under GLP conditions in a group of 10 Wistar rats (5 males and 5 female), treated with the limit dose 2000 mg/kg bw of the test substance in peanut oil by gavage. No mortality occurred and no clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed. No effect on body weight was noted and pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Therefore, under the conditions of this study, the oral LD50 in male and female rats was greater than 2000 mg/kg bw.

In summary, based on the available data on acute oral toxicity of the category members, the oral LD50 of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol is considered to be greater than 2000 mg/kg bw.

CAS 624-03-3

No studies are available investigating the acute oral toxicity of ethane-1,2-diyl palmitate. In order to fulfil the standard information requirements set out in Annex VII, 8.5, 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) was conducted.

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

Based on the available data on acute oral toxicity of the category members the oral LD50 of ethane-1,2-diyl palmitate is considered to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

CAS 627-83-8, CAS 68583-51-7, CAS 84988-75-0 and CAS 624-03-3

For acute inhalation toxicity, two studies are available within the Glycol ester category and were considered for assessment of all category members by read-across and a weight of evidence approach. The acute inhalation toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) was evaluated in two studies similar to OECD guideline 403 in a limit test (Re, 1978 a,b). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs and 3 control animals, respectively, were exposed whole body to 200 ppm (equivalent to 2.916 mg/L air) for 6 h. The animals were observed for a period of 7 days following administration.

No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. Necropsy revealed no substance-related findings in both studies.

Therefore, the LC50 for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L).

Acute dermal toxicity

CAS 627-83-8, CAS 68583-51-7, CAS 84988-75-0 and CAS 624-03-3

Data from the category members Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) investigating the acute toxicity via the dermal route are available and were considered for assessment of all category members by read-across and weight of evidence approach.

The acute dermal toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol, Butylene glycol dicaprylate / dicaprate and Octanoic acid ester with 1,2-propanediol, mono- and di were evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Potokar, 1989; Mürmann, 1992a,b).

Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under occlusive or semiocclusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted.

No substance-related findings during necropsy were observed in any animal (Mürmann, 1992a,b). In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point (Mürmann, 1992b).

The results of the three studies of the category substances consistently showed no effects at the limit dose 2000 mg/kg bw. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

Conclusion for acute toxicity

In summary, 15 studies are available studying the acute oral toxicity of Glycol Ester category members resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available within the Glycol Ester category. From these studies a LC50 value for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L) was obtained. Acute dermal toxicity data from three category members consistently showed no effects at the limit dose 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the category members and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

 

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 acute toxicity – oral endpoint
Hazard assessment is conducted means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and 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 acute oral and dermal toxicity 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.

Since the available acute inhalation studies provided LC50 values for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L), the data is inconclusive according to the classification criteria of Regulation (EC) 1272/2008 or Directive 67/548/EEC.