Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

The Short Chain Alcohol Esters (SCAE C2-C8) category covers esters from a fatty acid (C8-C29) and a C2-C8 alcohol (ethanol, isopropanol, butanol, isobutanol, pentanol, iso-pentanol, hexanol, 2-ethylhexanol or octanol). This category includes both well-defined mono-constituent substances as well as related UVCB substances with varying fatty acid chain lengths.

Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. isopropanol) 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 carboxylic 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 proton to give an ester (Liu et al, 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Monoesters are the final product of esterification.  

The rationale for grouping the substances in the SCAE C2-C8 category is based on similarities in physicochemical, ecotoxicological and toxicological properties.

 

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

 

In this particular case, the similarity of the SCAE C2-C8 category members is justified, in accordance with the specifications listed in Regulation (EC) No. 1907/2006 Annex XI, 1.5

Grouping of substances and read across, based on representative molecular structure, physico-chemical properties, tox-, ecotoxicological profiles, supported by a robust set of experimental data and QSAR calculations. There is no convincing evidence that any one of these chemicals might lie out of the overall profile of this category, respectively.

 

Grouping of substances into this category is based on:

 

 Similar/overlapping structural features or functional groups: All category members are esters of primary alcohols (C2-C8) and fatty acids (C8-C29), with 13 to 32 carbons in total.

 Common precursors and the likelihood of common breakdown products via biological processes: All category members are subject to enzymatic hydrolysis by pancreatic lipases (Mattson and Volpenhein, 1972; and references therein). The resulting free fatty acids and alcohols are absorbed from the intestine into the blood stream. Fatty acids are either metabolised via the beta-oxidation pathway in order to generate energy for the cell or reconstituted into glyceride esters and stored in the fat depots in the body. The alcohols are metabolised primarily in the liver through a series of oxidative steps, finally yielding carbon dioxide (Berg et al., 2002).

 Similar physico-chemical properties: The log Kow and log Koc values of all category members are high (log Kow > 4, log Koc > 3), increasing with the size of the molecule. The substances are poorly soluble in water and have low vapour pressure. 

 Common properties for environmental fate & eco-toxicological: Based on experimental data , all substances are readily biodegradable and do not show toxic effects up to the limit of water solubility.

 Common levels and mode of human health related effects:All available experimental data indicate that the members of the SCAE C2-C18 category are not acutely toxic, are not irritating to the skin or to the eyes and do not have sensitizing properties. Repeated dose toxicity was shown to be low for all substances. None of the substances showed mutagenic effects, and toxicity to reproduction was low throughout the category.

 

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are allocated to the category of SCAE C2-C8.

 

 

Table 1: Members of the SCAE C2-C8 Category

EC No.

CAS No.

Chemical name

Alcohol Carbon No.

Fatty acid Carbon No.

Total Carbon

MW

208-868-4

544-35-4

ethyl linoleate or ethyl octadeca-9,12-dienoate

2

18

20

308.50

203-889-5

111-62-6

Ethyl oleate

2

18

20

310.52

293-054-1

91051-05-7

Fatty acids, essential, ethyl esters

2

14 - 22

16 - 24

252.39-368.64

233-560-1

10233-13-3

Isopropyl laurate

3

12

15

242.41

203-751-4

110-27-0

Isopropyl Myristate

3

14

17

270.46

205-571-1

142-91-6

Isopropyl palmitate

3

16

19

298.51

269-023-3

68171-33-5

Isopropyl isostearate

3

18

21

326.56

203-935-4

112-11-8

Isopropyl oleate

3

18

21

324.55

292-962-5

91031-58-2

Fatty acids, C16-18, isopropyl esters

3

16 - 18

19 - 21

312.54-326.57

264-119-1

63393-93-1

Fatty acids, lanolin, isopropyl esters

3

10 - 29

13 - 32

214.34-480.85

204-666-5

123-95-5

butyl stearate

4

22

22

340.59

267-028-5

67762-63-4

Fatty acids, tall-oil, butyl esters

4

18

22

423.72

287-039-9

85408-76-0

Fatty acids, C16-18, Bu esters

4

16 - 18

20 - 22

312.53-340.58

284-863-0

84988-74-9

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

4

16 - 18

20 - 22

312.53- 340.58

 

163961-32-8

Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters

4

16 - 18

20 - 22

312.54- 340.58

211-466-1

646-13-9

Isobutyl stearate

4

18

22

340.59

288-668-1

85865-69-6

Fatty acids, C16-18, iso-Bu esters

4

16 - 18

20 - 22

312.54- 340.60

84988-79-4

84988-79-4

Fatty acids, C16-18 and C18-unsatd., iso-Bu esters

4

16 - 18

20 - 22

312.54- 340.60

228-626-1

6309-51-9

Isopentyl laurate

5

12

17

270.46

694-886-1

1365095-43-7

Fatty acids, C8-10, 3-methylbutyl esters

5

8 - 10

13 - 15

214.344- 242.40

251-932-1

34316-64-8

Dodecanoic acid, hexyl ester

6

12

18

284.49

218-980-5

2306-88-9

octyl octanoate

8

8

16

256.42

 

84713-06-4

Dodecanoic acid, isooctyl ester

8

12

20

312.53

243-697-9

20292-08-4

2-Ethylhexyl laurate

8

12

20

312.53

692-946-1

649747-80-8

Fatty acids, C8-10, 2-ethylhexyl esters

8

8 - 10

16 - 18

256.42-284.48

603-931-6

135800-37-2

Fatty acids, C8-16, 2-ethylhexyl esters

8

12 - 14

20 - 22

256.42-368.65

249-862-1

29806-73-3

2-ethylhexyl palmitate

8

16

24

368.64

 

22047-49-0

2-Ethyl hexyl Stearate

8

18

26

396.69

295-366-3

92044-87-6

Fatty acids, coco, 2-ethylhexyl esters

8

12 - 18

20 - 26

312.53-340.60

292-951-5

91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters

8

16 - 18

24 - 26

368.65-396.70

285-207-6

85049-37-2

Fatty acids, C16-18 and C18-unsatd., 2-ethylhexyl esters

8

16 - 18

24 - 26

368.65-396.70

247-655-0

26399-02-0

2-Ethylhexyl oleate

8

18

26

394.67

 

In order to avoid the need to test every substance for every endpoint, 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).

Table 2: Reproductive toxicity

CAS #

Toxicity

111-62-6 (a)

NOAEL: 5500 mg/kg bw/day

123-95-5 (a)

NOAEL: 6000 mg/kg bw/day

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

CAS 111-62-6

NOAEL (fertility) = 5500 mg/kg bw/day, OECD 408

A 90-day oral feeding study (Bookstaff, 2004) was performed with Ethyl Oleate (CAS# 111-62-6) according to the 1993 FDA draft "Redbook II" guidelines (Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food). The study was performed equivalently to OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents) with additional assessment of oestrus cycle and sperm parameters. The purpose of the study was to determine the safety of Ethyl Oleate (EO) in a 91-day feeding study in Sprague-Dawley rats. EO was mixed into AIN-93G purified diet at levels of approx. 0, 1900, 3800 and 6000 mg/kg bw/day. All diets were calorie- and fat-matched using high oleic safflower oil (HOSO) as the control fat. There were 20 male and 20 female rats per group. EO in the diet was well tolerated and there were no toxicologically significant findings in any of the measured parameters (clinical observations, body weight gains, appearance of the faeces, ophthalmic examinations, haematology, clinical chemistry, urinalysis, organ weights, histopathology, or male and female reproductive assessments). Based on the absence of abnormalities concerning oestrus cyclus, sperm characterization and histopathologic evaluation of oestrus cycle in females, sperm characterization in males and histologic examinations (incl. epididymides, mammary gland, ovaries, prostate, seminal vesicles, testes, thyroid with parathyroid, uterus with uterine horns and Vagina) the subchronic 90-day oral NOAEL for fertility in rats for Ethyl Oleate was found to be approx. 5500 mg/kg bw/d.

 

CAS 123-95-5 

NOAEL (parental fertility) = 6000 mg/kg bw/day, OECD 421

NOAEL (offspring development) = 6000 mg/kg bw/day, OECD 421

A reproduction/developmental toxicity screening test was performed with Butyl Stearate (CAS# 123-95-5) similar to OECD Guideline 421 (Smith, 1953). 20 male and female Sprague-Dawley rats received Butyl Stearate at a concentration of 6.25% in the diet, corresponding to approx. 6000 mg/kg bw/day for a period of 10 weeks. Negative control animals (12 males and females) were fed with the concurrent basal diet. After 10 weeks animals were mated. Successfully mated pregnant females were housed individually in breeding cages. The date of parturition and the number and sex of pups in each litter were recorded. Litters were weaned 21 days postpartum and the weights of the weanlings determined. From each of the three groups of weanlings (those receiving the test material and the controls), 24 males and 24 females were chosen at random and for the next 21 days, these young were fed the same 6.25% diet as had been ingested by their parents. Diet intake and body weights were recorded daily; 21 days after weaning, the rats were sacrificed and necropsies were performed.

Based on reproduction, fertility index, litter size, survival index/viability index of offspring and necropsy at day 21 after weaning the NOAEL for parental fertility as well as for offspring development was found to be 6000 mg/kg bw/d.

 

Conclusion for reproduction toxicity

Two studies investigating the reproduction toxicity are available within theShort Chain Alcohol Esters (SCAE C2-C8). The studies from the category members Ethyl Oleate (CAS# 111-62-6) and Butyl Stearate (CAS# 123-95-5) did not show treatment-related effects up to the highest tested dose level. Thus, no hazard for reproduction toxicity was identified.

 

 

References:

*Berg, J.M., Tymoczko, J.L. and Stryer, L., 2002, Biochemistry, 5thedition, W.H. Freeman and Company

*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

*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.

*Mattson, F.H. and Volpenheim, R.A. (1972): Relative rates of hydrolysis by rat pancreatic lipase of esters of C2-C18 fatty acids with C1-C18 primary n-alcohols,Journal of Lipid Research, 10, 1969

*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.

*Tocher, D.R. (2003):Metabolism and function of lipids and fatty acids in teleost fish,Reviews of Fisheries Science, 11 (2), 197

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


Short description of key information:
Studies on reproduction toxicity/fertility were available for the following category members (CAS#): 111-62-6 and 123-95-5.
For ethyl oleate and butyl stearate a 90-day subchronic NOAEL for fertility was found to be 5500 and 6000 mg/kg bw/d in rats.

Effects on developmental toxicity

Description of key information
The NOAEL for maternal and developmental toxicity for 2-ethylhexylstearate (CAS# 91031-48-0) and for 2-ethyl hexyl stearate (CAS# 22047-49-0) was found to be 1000 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The Short Chain Alcohol Esters (SCAE C2-C8) category covers esters from a fatty acid (C8-C29) and a C2-C8 alcohol (ethanol, isopropanol, butanol, isobutanol, pentanol, iso-pentanol, hexanol, 2-ethylhexanol or octanol). This category includes both well-defined mono-constituent substances as well as related UVCB substances with varying fatty acid chain lengths.

Fatty acid esters are generally produced by chemical reaction of an alcohol (e.g. isopropanol) 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 carboxylic 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 proton to give an ester (Liu et al, 2006; Lilja et al., 2005; Gubicza et al., 2000; Zhao, 2000). Monoesters are the final product of esterification.  

The rationale for grouping the substances in the SCAE C2-C8 category is based on similarities in physicochemical, ecotoxicological and toxicological properties.

 

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

 

In this particular case, the similarity of the SCAE C2-C8 category members is justified, in accordance with the specifications listed in Regulation (EC) No. 1907/2006 Annex XI, 1.5

Grouping of substances and read across, based on representative molecular structure, physico-chemical properties, tox-, ecotoxicological profiles, supported by a robust set of experimental data and QSAR calculations. There is no convincing evidence that any one of these chemicals might lie out of the overall profile of this category, respectively.

 

Grouping of substances into this category is based on:

 

 Similar/overlapping structural features or functional groups: All category members are esters of primary alcohols (C2-C8) and fatty acids (C8-C29), with 13 to 32 carbons in total.

 Common precursors and the likelihood of common breakdown products via biological processes: All category members are subject to enzymatic hydrolysis by pancreatic lipases (Mattson and Volpenhein, 1972; and references therein). The resulting free fatty acids and alcohols are absorbed from the intestine into the blood stream. Fatty acids are either metabolised via the beta-oxidation pathway in order to generate energy for the cell or reconstituted into glyceride esters and stored in the fat depots in the body. The alcohols are metabolised primarily in the liver through a series of oxidative steps, finally yielding carbon dioxide (Berg et al., 2002).

 Similar physico-chemical properties: The log Kow and log Koc values of all category members are high (log Kow > 4, log Koc > 3), increasing with the size of the molecule. The substances are poorly soluble in water and have low vapour pressure. 

 Common properties for environmental fate & eco-toxicological: Based on experimental data , all substances are readily biodegradable and do not show toxic effects up to the limit of water solubility.

 Common levels and mode of human health related effects:All available experimental data indicate that the members of the SCAE C2-C18 category are not acutely toxic, are not irritating to the skin or to the eyes and do not have sensitizing properties. Repeated dose toxicity was shown to be low for all substances. None of the substances showed mutagenic effects, and toxicity to reproduction was low throughout the category.

 

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be considered as a category provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances listed below are allocated to the category of SCAE C2-C8.

 

 

Table 1: Members of the SCAE C2-C8 Category

EC No.

CAS No.

Chemical name

Alcohol Carbon No.

Fatty acid Carbon No.

Total Carbon

MW

208-868-4

544-35-4

ethyl linoleate or ethyl octadeca-9,12-dienoate

2

18

20

308.50

203-889-5

111-62-6

Ethyl oleate

2

18

20

310.52

293-054-1

91051-05-7

Fatty acids, essential, ethyl esters

2

14 - 22

16 - 24

252.39-368.64

233-560-1

10233-13-3

Isopropyl laurate

3

12

15

242.41

203-751-4

110-27-0

Isopropyl Myristate

3

14

17

270.46

205-571-1

142-91-6

Isopropyl palmitate

3

16

19

298.51

269-023-3

68171-33-5

Isopropyl isostearate

3

18

21

326.56

203-935-4

112-11-8

Isopropyl oleate

3

18

21

324.55

292-962-5

91031-58-2

Fatty acids, C16-18, isopropyl esters

3

16 - 18

19 - 21

312.54-326.57

264-119-1

63393-93-1

Fatty acids, lanolin, isopropyl esters

3

10 - 29

13 - 32

214.34-480.85

204-666-5

123-95-5

butyl stearate

4

22

22

340.59

267-028-5

67762-63-4

Fatty acids, tall-oil, butyl esters

4

18

22

423.72

287-039-9

85408-76-0

Fatty acids, C16-18, Bu esters

4

16 - 18

20 - 22

312.53-340.58

284-863-0

84988-74-9

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

4

16 - 18

20 - 22

312.53- 340.58

 

163961-32-8

Fatty acids, C16-18 and C18 unsatd. branched and linear, butyl esters

4

16 - 18

20 - 22

312.54- 340.58

211-466-1

646-13-9

Isobutyl stearate

4

18

22

340.59

288-668-1

85865-69-6

Fatty acids, C16-18, iso-Bu esters

4

16 - 18

20 - 22

312.54- 340.60

84988-79-4

84988-79-4

Fatty acids, C16-18 and C18-unsatd., iso-Bu esters

4

16 - 18

20 - 22

312.54- 340.60

228-626-1

6309-51-9

Isopentyl laurate

5

12

17

270.46

694-886-1

1365095-43-7

Fatty acids, C8-10, 3-methylbutyl esters

5

8 - 10

13 - 15

214.344- 242.40

251-932-1

34316-64-8

Dodecanoic acid, hexyl ester

6

12

18

284.49

218-980-5

2306-88-9

octyl octanoate

8

8

16

256.42

 

84713-06-4

Dodecanoic acid, isooctyl ester

8

12

20

312.53

243-697-9

20292-08-4

2-Ethylhexyl laurate

8

12

20

312.53

692-946-1

649747-80-8

Fatty acids, C8-10, 2-ethylhexyl esters

8

8 - 10

16 - 18

256.42-284.48

603-931-6

135800-37-2

Fatty acids, C8-16, 2-ethylhexyl esters

8

12 - 14

20 - 22

256.42-368.65

249-862-1

29806-73-3

2-ethylhexyl palmitate

8

16

24

368.64

 

22047-49-0

2-Ethyl hexyl Stearate

8

18

26

396.69

295-366-3

92044-87-6

Fatty acids, coco, 2-ethylhexyl esters

8

12 - 18

20 - 26

312.53-340.60

292-951-5

91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters

8

16 - 18

24 - 26

368.65-396.70

285-207-6

85049-37-2

Fatty acids, C16-18 and C18-unsatd., 2-ethylhexyl esters

8

16 - 18

24 - 26

368.65-396.70

247-655-0

26399-02-0

2-Ethylhexyl oleate

8

18

26

394.67

 

In order to avoid the need to test every substance for every endpoint, 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).

 

Table 2: Developmental toxicity

CAS #

Toxicity

22047-49-0 (a)

NOAEL: 1000 mg/kg bw/day

91031-48-0 (a)

NOAEL: 1000 mg/kg bw/day

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

 

CAS 22047-49-0

NOAEL (maternal toxicity) = 1000 mg/kg bw/day, OECD 414

NOAEL (embryo-/fetotoxicity and teratogenicity) = 1000 mg/kg bw/day, OECD 414

The developmental toxicity of 2-Ethylhexyl Stearate (CAS 22047-49-0) was investigated according to OECD Guideline 414 and GLP conditions (Aulmann, 2000). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/d during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/d. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/fetotoxicity and teratogenicity in rats for 2-Ethylhexyl Stearate was found to be 1000 mg/kg bw/day.

 

 

CAS 91031-48-0

NOAEL (maternal toxicity) = 1000 mg/kg bw/day, OECD 414

NOAEL (embryo-/fetotoxicity and teratogenicity) = 1000 mg/kg bw/day, OECD 414

A Prenatal Developmental Toxicity Study was performed with Fatty Acids, C16-18, 2-Ethylhexyl Esters (CAS 91031-48-0) according to OECD Guideline 414 (Pittermann, 1994). Groups of 24 female Sprague-Dawley rats received daily oral gavage doses of the test substance in arachidis oil at dose levels of 0, 100, 300 and 1000 mg/kg bw/day during gestational days 6 to 15. On day 20 of gestation the animals were euthanized and examined for maternal and fetal parameters. Based on the number of implantations, number of total litter losses by resorption, mortality, clinical signs, body weight, gross pathology and organ weights of maternal animals the NOAEL for maternal toxicity was found to be 1000 mg/kg bw/day. Examination of fetus litter size and weights, offspring viability (number alive and number dead), sex ratio, grossly visible abnormalities, external, head, soft tissue and skeletal abnormalities showed no differences to control and no indication for teratogenic effects. Therefore, the NOAEL for embryo-/foetotoxicity and teratogenicity in rats for Fatty Acids C16-18, 2-Ethylhexyl Esters was found to be 1000 mg/kg bw/day.

 

 

Conclusion for developmental toxicity

Two studies investigating the developmental toxicity are available within theShort Chain Alcohol Esters (SCAE C2-C8). The studies from the category members2-Ethylhexyl Stearate (CAS 22047-49-0) and Fatty Acids, C16-18, 2-Ethylhexyl Esters (CAS 91031-48-0)did not show treatment-related effects up to the highest tested dose level. Thus, no hazard for developmental toxicity was identified.

 

References:

*Berg, J.M., Tymoczko, J.L. and Stryer, L., 2002, Biochemistry, 5thedition, W.H. Freeman and Company

*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

*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.

*Mattson, F.H. and Volpenheim, R.A. (1972): Relative rates of hydrolysis by rat pancreatic lipase of esters of C2-C18 fatty acids with C1-C18 primary n-alcohols,Journal of Lipid Research, 10, 1969

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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 SCAE C2-C8 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.

The available data on reproduction toxicity is conclusive but not sufficient for classification.

Additional information

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