Registration Dossier

Administrative data

Description of key information

Based on a weight of evidence approach, fatty acid methyl esters showed no irritating potential to human skin.
All available studies on the acute eye irritation potential of fatty acid methyl esters showed no irritating potential to the eye in vivo.

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

The short chain fatty acid methyl esters category (SCAE Me) covers fatty acid esters of methanol. The category contains both mono-constituent substances, with fatty acid C-chain lengths ranging from C6 to C18 and UVCB substances, composed of single methyl esters in variable proportions. Fatty acid esters are generally produced by chemical reaction of an alcohol (methanol) with an organic acid (e.g. octanoic 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. 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 products of esterification.

SCAE Me esters category members include:

Mono-constituent substances:

* Hexanoic acid, methyl ester (CAS No.): 106-70-7 - (MW 130.19)

* Octanoic acid, methyl ester (CAS No.): 111-11-5 - (MW 158.24)

* Decanoic acid, methyl ester (CAS No.): 110-42-9 - (MW 186.29)

* Dodecanoic acid, methyl ester (CAS No.): 111-82-0 - (MW 214.35)

* Tetradecanoic acid, methyl ester (CAS No.): 124-10-7 - (MW 242.40)

* Hexadecanoic acid, methyl ester (CAS No.): 112-39-0 - (MW 270.46)

* Octadecanoic acid, methyl ester (CAS No.): 112-61-8 - (MW 298.51)

* 9-Octadecenoic acid (Z)-, methyl ester (CAS No.): 112-62-9 - (MW 294.48)

* 9, 12-Octadecadienoic acid (Z, Z)-, methyl ester (CAS No.): 112-63-0 - (MW 294.48)

* Hexadecanoic acid (CAS No.): 57-10-3 - (MW 256.43).

UVCB´s:

* Fatty acids, C6-10, methyl esters (CAS No.): 68937-83-7 - (MW 130.19-186.29)

* Fatty acids, C8-10, methyl esters (CAS No.): 85566-26-3 - (MW 158.24-186.29)

* Fatty acids, C10-16, methyl esters (CAS No.): 67762-40-7 - (MW 186.29-270.46)

* Fatty acids, C12-14 (even numbered), methyl esters (CAS No.): 308065-15-8 - (MW 214.35-242.40)

* Fatty acids, C8-18 and C18-unsatd., methyl ester (CAS No.): 67762-37-2 - (MW 158.24-298.51)

* Fatty acids, C12-18, methyl esters (CAS No.): 68937-84-8 - (MW 214.35-298.51)

* Fatty acids, 12-16 and C18-unsatd., methyl esters (CAS No.): 1234694-02-0 - (MW 214.35-298.51)

* Fatty acids, C16-18, methyl esters (CAS No.): 85586-21-6 - (MW 270.46-298.51)

* Fatty acids, palm-oil, methyl esters (CAS No.): 91051-34-2 - (MW 242.40-298.51)

* Fatty acids, C16-18 and C18-unsatd, methyl esters (CAS No.): 67762-38-3 - (MW -270.46-298.51)

* Fatty acids, C14-18 and C16-18-unsatd., methyl esters (CAS No.): 67762-26-9 - (MW 130.19–290.51)

* Fatty acids, coco, Me esters (CAS No.): 61788-59-8 - (MW 214.35-270.46)

* Fatty acids, tallow, Me esters (CAS No.): 61788-61-2 - (MW 242.40-298.51).

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 environmental fate and ecotoxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structural related substances (grouping or read-across)”.

In this particular case, the similarity of the SCAE Me category members is justified in accordance with the specifications listed in Regulation (EC) No 1907/2006, Annex XI, 1.5. The key points the members of the category members share are:

* Common origin:Fatty acid esters (C6-C18) of methanol

* Common precursors and the likelihood of common breakdown products:Fatty acid methyl esters are hydrolysed to the corresponding alcohol (methanol) and fatty acid by esterases (Fukami and Yokoi, 2012), even though it was shown in-vitro that the hydrolysis rate of methyl oleate was lower when compared with the hydrolysis rate of the triglyceride Glycerol trioleate (Mattson and Volpenhein, 1972). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: After oral ingestion, esters of methanol and fatty acids will undergo chemical changes already in the gastro-intestinal fluids as a result of enzymatic hydrolysis. In contrast, substances that are absorbed through the pulmonary alveolar membrane or through the skin enter the systemic circulation directly before entering the liver where hydrolysis will basically take place. The first cleavage product, the fatty acid, is stepwise degraded by beta-Oxidation based on enzymatic removal of C2units in the matrix of the mitochondria in most vertebrate tissues. The C2units are cleaved as acyl-CoA, the entry molecule for the citric acid cycle. For the complete catabolism of unsaturated fatty acids such as oleic acid, an additional isomerization reaction step is required (see figure below). The alpha- and omega-oxidation, alternative pathways for oxidation, can be found in the liver and the brain, respectively (CIR, 1987). For the second cleavage product methanol, the metabolism is predominating: Initially, methanol is slowly oxidized in the liver by the enzyme alcohol dehydrogenase (ADH) to formaldehyde, which itself is oxidized very rapidly by the enzyme aldehyde dehydrogenase (ALDH) to formic acid. Finally, formic acid is slowly metabolised to CO2and H2O (ICPS, 2002).

* Consistent trends in physico-chemical properties:Water solubility values of the category members tend to decrease at increasing fatty acid C-chain lengths, ranging from 1330 mg/L (C6) to 0.0003 mg/L for C18, whereas partition coefficient values, as expected, increase at increasing C-chain lengths (ranging from 2.3 for C6 to 8.3 for C18). Adsorption to soil and sediment particles is a relevant property for substances containing C8 fatty acids onwards (log Kow > 3). Only the substance with the shortest fatty acid chain length (C6) is considered to have low adsorption potential (log Kow = 2.3). Vapour pressure decreases at increasing chain lengths (ranging from 496 Pa (C6) to 0.00018 Pa (C18) at 25°C). In view of the values reported for C6, C8 (71.9 Pa) and C10 (4.9 Pa), at least partial volatilization of substances containing these fatty acids can be expected. Due to their structural similarities, all category members show consistent trends and therefore, a regular pattern in their physico-chemical properties. Therefore, in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5, these substances may be considered as a category.

* Consistent trends in environmental fate and ecotoxicological profile:The members of the SCAE Me category are readily biodegradable and show low bioaccumulation potential in biota (due to metabolism). The water solubility of the mono-constituent substances within the category decreases at increasing C-chain lengths with a turning point from water soluble to insoluble observed at C14 (water solubility 0.05 mg/L). For the substances containing C6, C8, C10 and C12 fatty acids, water solubilities of 1330 mg/L, 64.4 mg/L, 10.6 mg/L and 7.76 mg/L have been reported respectively. Substances containing C-chain lengths > C14 are insoluble in water, including all UVCB substances within the category (water solubilities < 1 mg/L). Nevertheless, regardless the main environmental compartment of concern (water, soil, sediment) the SCAE Me´s will not be persistent in the environment considering their readily biodegradable nature.Regarding the aquatic toxicity profile in the category, no acute toxicity to fish species is observed. On the other hand, the short-term tests conducted with aquatic invertebrates (Daphnia) and algae for the mono-constituent substances show a toxicity trend. The toxicity increases at increasing C-chain length (starting from C8) up to a toxicity peak at C12 (for which L(E)C50s and NOECs < 1 mg/L have been reported). With decreasing water solubility at longer C-chain lengths (C14), no toxicity up to the highest attainable concentration is observed in Daphnia and algae. For the UVCBs, in those cases where toxicity data are not available, structurally related read-across substances are used in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5: either mono-constituent substances (considering the predominant fatty acid chain lengths in the UVCB) or other analogue UVCBs.

Due to the structural similarities and consistent trend in physico-chemical properties and available data on skin and eye irritation, the members of the SCAE Me category can be considered as a category of substances, according to Regulation (EC) No. 1907/2006, Annex XI, 1.5. A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) as well as in the Chemical Safety Report (see Part B).

References:

* CIR (1987). Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, stearic acid. J. of the Am. Coll. of Toxicol.6 (3): 321-401.

* Fukami, T. and Yokoi, T. (2012). The Emerging Role of Human Esterases. Drug Metabolism and Pharmacokinetics, Advance publication July 17th, 2012.

* 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, ICPS (2002). Poisons Information Monograph 335, Methanol. http://www.inchem.org/documents/pims/chemical/pim335.htm

* 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 Volpenhein, R.A. (1972). Hydrolysis of fully esterified alcohols containing from one to eight hydroxyl groups by the lipolytic enzymes of the rat pancreatic juice. Journal of lipid research 13: 325-328

* 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

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

Skin Irritation

Since no studies investigating the skin irritation of fatty acids, C16-18, methyl esters (CAS 85586-21-6) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related category members methyl octanoate (CAS 111-11-5), decanoic acid, methyl ester (CAS 110-42-9), methyl laurate (CAS 111-82-0), methyl palmitate (CAS 112-39-0), methyl hexanoate (CAS 106-70-7), methyl myristate (C14, CAS No. 124-10-7), methyl oleate (CAS No. 112-62-9), methyl stearate (CAS 112-61-8), fatty acids, C16-18 and C18-unsatd., methyl esters (CAS No. 67762-38-3), fatty acids, C14-18 and C16-18-unsatd., methyl esters (CAS 67762-26-9) and methyl linoleate (CAS 112-63-0) was conducted.

 

CAS #,

Carbon range

Skin irritation

106-70-7

(C6)

Experimental result: not irritating to human and rabbit skin

111-11-5

(C8)

Experimental result: not irritating to human skin

110-42-9

(C10)

Experimental result: not irritating to human skin

111-82-0

(C12)

Experimental result: not irritating to human skin; ambiguous for rabbit skin

124-10-7

(C14)

Experimental result: not irritating to human skin

112-39-0

(C16)

Experimental result: not irritating to human skin; irritating to rabbit skin

112-61-8

(C18)

Experimental result: not irritating to rabbit skin

112-63-0

(C18’’)

Not to be registered

112-62-9

(C18’)

Experimental result: not irritating to human skin

85566-26-3

(C8-C10)

RA from 111-11-5 and 110-42-9: not irritating to human skin

67762-40-7

(C10-C16)

RA from 111-42-9 and 112-39-0: not irritating to human skin

308065-15-8

(C12-C14)

RA from 111-42-9 and 112-39-0: not irritating to human skin

68937-83-7

(C6-C10)

Not to be registered

 

67762-37-2

(C8-C18, C18uns)

Not to be registered

 

68937-84-8

(C12-C18)

RA from 111-82-0 and 112-62-9: not irritating to human skin

1234694-02-0

(C12-C16, C18uns)

RA from 111-82-0 and 112-62-9: not irritating to human skin

85586-21-6(C16-C18)

RA from 67762-38-3: not irritating to rabbit skin

91051-34-2

(C14-C18, C18uns)

RA from 112-39-0 and 67762-26-9: not irritating to human skin

67762-38-3

(C16-C18, C18uns)

Experimental result: not irritating to rabbit skin

67762-26-9

(C14-C18, C18uns)

Experimental result: not irritating to human and rabbit skin

61788-59-8

(C12-C16)

Not to be registered

 

 

 

Skin irritation - Human Data

 

Several fatty acid methyl esters were tested in vivo on human skin. None of the tested fatty acid methyl esters showed any relevant skin irritation potential on human skin:

 

CAS 106-70-7, CAS 111-11-5, CAS 110-42-9,  CAS 111-82-0, CAS 124-10-7, CAS 112-39-0 and CAS 112-62-9

A reliable human volunteer study was performed (Kremer, 1998) to investigate the skin irritation potential of methyl caproate (C6, CAS No. 106-70-7), methyl caprylate (C8, CAS No. 111-11-5), methyl decanoate (C10, CAS No. 110-42-9), methyl laurate (C12, CAS No. 111-82-0), methyl myristate (C14, CAS No. 124-10-7), methyl palmitate (C16, CAS No. 112-39-0) and methyl oleate (CAS No. 112-62-9). Different fatty acid methyl esters were tested in 20 human volunteers for their skin irritation potential according to COLIPA under GCP conditions. The dorsal skin was exposed to 70μL of the undiluted test substances for 24 hours under occlusive conditions using Finn Chambers on Scanpor. Reference substances including Texapon N28 (tenside standard with good skin compatibility), sodium-dodecylsulfate, cosmetic alcohol, physiological saline and paraffin oil were tested concurrently. Skin reactions (erythema, oedema, eschar and fissure formations) were assessed 6, 24, 48 and 72 hours after patch removal according to the system of Frosch and Kligman (1979). The skin compatibility towards methyl caproate (C6) was comparable with Texapon N 28 and thus found to be satisfying. Good skin compatibility was found towards methyl caprylate (C8), methyl decanoate (C10), methyl laurate (C12), methyl myristate (C14) and methyl palmitate (C16). Very good skin compatibility was found for methyl oleate (C18). The 4 hour testing method under occlusive conditions in 20 human volunteers was found to be sufficient for hazard assessment of the tested substances.

 

CAS 111-82-0

Another human volunteer study was performed (Krächter 1994) to investigate the skin irritation potential of methyl laurate (C12, CAS No. 111-82-0). 60 healthy volunteers were tested for skin irritation potential of the test material in an open epicutaneous test according to the method described by Burckhard (Burckhard 1964. Dermatologica 129: 37-46). The test material was applied at concentrations of 10 and 20 (20 volunteers), 50 (20 volunteers) and 100 % (20 volunteers) onto the skin of the volunteers every 30 sec for a time of overall 30 min on the inside of the forearm of the volunteers under open conditions. None of the volunteers showed any signs of irritation at any concentration tested.

 

CAS 112-39-0

In a third human volunteer study (Matthies 1988) the skin irritation potential of methyl palmitate (C16, CAS No. 112-39-0) and fatty acids, C14-C18 and C16-C18 unsaturated, methyl esters (CAS No. 67762-26-9) was investigated. In a modified Duhring-chamber test 20 healthy volunteers were applied 70 µL of a 50 % dilution of the test substance as a single application on the back for 24 h with occlusive patches (i.e. Fin Chamber on Scanpor). There were only very slight reactions observed for erythema, edema, scale and fissuring. The irritation index of both test materials was much lower than that of the internal standard (positive control) 1% Texapon N 25, no signs for skin irritation were found.

 

 

 

 

Skin irritation - Animal Data

Several fatty acid methyl esters were tested in vivo on rabbit skin. Some of the studies results indicated no skin irritation potential, while other studies indicated a skin irritation potential on rabbit skin:

 

 

CAS 111-82-0 

Two animal studies investigating the skin irritation of methyl laurate are available (CAS 111-82-0). In a primary dermal irritation study, the skin irritation/corrosion potential of methyl laurate (CAS 111-82-0) was tested according to OECD Guideline 404 (Busschers, 1998). The shaved dorsal skin of three male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. After exposure remaining test substance was removed by wiping with a moistened tissue. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours and 7 days after removal of the test substance. The exposure period of four hours resulted in well defined or moderate to severe erythema and moderate oedema in the treated skin-areas of all three rabbits. The skin irritation had resolved within 7 days after exposure in all animals. At the end of the observation period, scaliness was noted in all animals and in addition bald skin at the edges of the application area was noted in two animals.

 

In another study, the skin corrosion potential of methyl laurate (CAS 111-82-0) was tested according to D.O.T. Corrosivity, 49 CFR 173.240 (Hiles, 1982). 0.5 mL of the unchanged test substance was applied to the shaved back of 6 New Zealand White rabbits for 4 hours under occlusive conditions. The animals were observed for 48 hours. The skin evaluated for corrosion immediately after patch removal and after 44 h (48 h after application). The test substance caused only slight erythema, which persisted to the end of the observation period. No oedema occurred in any of the 6 tested animals.

 

 

CAS 112-39-0 

Methyl palmitate (CAS No. 112-39-0) was investigated in a primary skin irritation study according to OECD 404 (Steiling, 1992). The shaved dorsal skin of three Klein-russen rabbits was exposed to 0.5 g unchanged pasty test material for 4 hours under semi-occlusive conditions. After exposure the skin was cleaned from the residual test substance. The rabbits were observed for 21 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7, 14 and 21 days after removal of the test substance. The exposure period of four hours resulted in strong skin irritation in all animals that persisted as slight erythema in one animal to the end of the observation period of 21 days.

 

 

 

CAS 106-70-7 

For methyl hexanoate (CAS No. 106-70-7), a primary skin irritation study according to OECD Guideline 404 (Pittermann, 1992) was performed under GLP conditions. The shaved dorsal skin of three Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 22 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7, 14 and 22 days after removal of the test substance. Slight to weak erythema and oedema were observed in all three animals during the first 72 h after exposure. One week after exposure the skin of one experimental animal showed eschar formation. The observed skin effects were fully reversible within 14 days in two animals. In the third animal slight skin irritation persisted longer than the observation period of 22 days.

 

 

CAS 112-61-8 

A primary dermal irritation study was performed with methyl stearate (CAS No. 112-61-8) according to OECD Guideline 404 (Steiling, 1992). The shaved dorsal skin of three Klein-russen rabbits was exposed to 0.5 g unchanged test material for 4 hours under semi-occlusive conditions. After exposure the skin was cleaned from the residual test substance. The rabbits were observed for 21 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7, 14 and 21 days after removal of the test substance. The exposure period of four hours caused slight to moderate skin erythema to all three animals. In one animal a slight erythema persisted to the end of the observation period of 21 days. In two animals the skin irritation was fully reversible within 21 days.

 

 

CAS 67762-26-9 

Another primary dermal irritation study was performed with Fatty acids, C14-18 and C16-18-unsatd., Methyl esters (CAS No. 67762-26-9) according to OECD Guideline 404 (Kästner, 1988). The shaved dorsal skin of three Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 10 days. Skin reactions were assessed using the Draize scheme 24, 48, 72 hours after removal of the test substance. Slight to weak erythema and oedema were observed in all three animals, which was fully reversible in a time period between 1 and 10 days.

 

 

CAS 67762-38-3 

For fatty acids, C16-18 and C18-unsatd., methyl esters (CAS No. 67762-38-3), a primary dermal irritation study according to OECD Guideline 404 (Steiling, 1992) was performed. The shaved dorsal skin of three Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 72 hours. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours after removal of the test substance. The exposure period of four hours under semi-occlusive conditions caused only slight erythema in two out of three animals, which was fully reversible within 72 hours. No oedema occurred in any of the treated skin sites.

 

 

CAS 112-63-0 

A primary dermal irritation study was performed withmethyl linoleate (CAS 112-63-0) according to OECD guideline 404 (BASF 1992). The shaved dorsal skin of three Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 22 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours after removal of the test substance. After a exposure period of 4 hours slight to moderate erythema and oedema were observed in all three animals. All irritation effects were fully reversible in a time period between 7 and 22 days.

 

 

CAS 112-61-8 

Methyl stearate (CAS No. 112-61-8) was investigated in a dermal irritation study according to OECD Guideline 404 (Steiling, 1992). The shaved dorsal skin of three Klein-russen rabbits was exposed to 0.5 g unchanged test material for 4 hours under semi-occlusive conditions. After exposure the skin was cleaned from the residual test substance. The rabbits were observed for 21 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7, 14 and 21 days after removal of the test substance. The exposure period of four hours caused slight to moderate skin erythema to all three animals. In one animal a slight erythema persisted to the end of the observation period of 21 days. In two animals the skin irritation was fully reversible within 21 days.

 

 

 

According to the ECETOC Monograph No. 32, ISSN-0773-6347-32 (Ecetoc, 2002) on the use of Human Data in Hazard Classification for Irritation and Sensitisation, comparative testing with rabbits and human volunteers exhibits clear differences in susceptibility to some classes of irritant substances and preparations, amongst others for short chain fatty acid methyl esters. Human skin is, in general, less affected. This may be related mainly to physiological differences between species.

A classification for skin irritation would be appropriate for some short chain fatty acid methyl esters, based on the rabbit skin reactions, but is unnecessary according to the results on human skin. Therefore, based on a weight of evidence approach, no classification for skin irritation for all substances within the fatty acid methyl esters category is required.

 

 

 

 

 

Eye irritation

 

Since no studies investigating the eye irritation of fatty acids, C16-18, methyl esters (CAS 85586-21-6) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across to the structurally related category members methyl laurate (CAS 111-82-0), methyl palmitate (CAS 112-39-0), methyl hexanoate (CAS 106-70-7), fatty acids, C6-10, methyl esters (CAS No. 68937-83-7), methyl stearate (CAS 112-61-8) and fatty acids, C14-18 and C16-18-unsatd., methyl esters (CAS 67762-26-9) was conducted.

 

CAS #,

Carbon range

Eye irritation

106-70-7

(C6)

Experimental result: not irritating to rabbit eye in vivo

111-11-5

(C8)

RA from 106-70-7 and 68937-83-7: not irritating

110-42-9

(C10)

RA from 106-70-7 and 68937-83-7: not irritating

111-82-0

(C12)

Experimental result: not irritating to rabbit eye in vivo

124-10-7

(C14)

RA from 111-82-0: not irritating

112-39-0

(C16)

Experimental result: not irritating to rabbit eye in vivo

112-61-8

(C18)

Experimental result: not irritating to rabbit eye in vivo

112-63-0

(C18’’)

Not to be registered

112-62-9

(C18’)

RA from 91051-34-2: not irritating

85566-26-3

(C8-C10)

RA from 68937-83-7: not irritating to rabbit eye in vivo

67762-40-7

(C10-C16)

RA from 111-82-0: not irritating to rabbit eye in vivo

308065-15-8

(C12-C14)

RA from 111-82-0 and 112-39-0: not irritating to rabbit eye in vivo

68937-83-7

(C6-C10)

Experimental result: not irritating to rabbit eye in vivo

67762-37-2

(C8-C18, C18uns)

Not to be registered

68937-84-8

(C12-C18)

RA from 111-82-0: not irritating to rabbit eye in vivo

1234694-02-0

(C12-C16, C18uns)

RA from 111-82-0. 67762-26-9 and 112-61-8: not irritating to rabbit eye in vivo

85586-21-6(C16-C18)

RA from 112-39-0 and 112-61-8: not irritating to rabbit eye in vivo

91051-34-2

(C14-C18, C18uns)

Experimental result: not irritating to rabbit eye in vivo

67762-38-3

(C16-C18, C18uns)

RA from 91051-34-2: not irritating to rabbit eye in vivo

67762-26-9

(C14-C18, C18uns)

Experimental result: not irritating to rabbit eye in vivo

61788-59-8

(C14-C16)

Not to be registered

 

 

 

 

 

CAS 111-82-0 

Two animal studies investigating the eye irritation of methyl laurate (CAS 111 -82 -0) are available.An acute eye irritation study was performed with methyl laurate (CAS 111-82-0) according to OECD Guideline 405 (Steiling, 1992). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye of three Kleinrussen rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 1, 24, 48 and 72 hours after application. Mild redness of conjunctiva and lacrimation was observed in one out of three tested animals, which was fully reversible within 72 hours.

 

Methyl laurate (CAS 111-82-0) was tested in another study performed similar to OECD Guideline 405 (Hiles, 1982). 0.1 mL of the unchanged test substance was instilled to the conjunctival sac of one eye of 3 New Zealand White rabbits. At 24 hours after instillation no eye reaction occurred in any of the treated animals. Due to the lack of any eye reaction, the observation period was ended at this time point.

 

 

CAS 112-39-0 

Methyl palmitate (CAS 112-39-0) was tested for its eye irritation potential according to OECD Guideline 405 (Steiling, 1992). 0.1 mL of the undiluted test substance was instilled into the right conjunctival sac of three Kleinrussen rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 24, 48 and 72 hours after application. Mild redness of conjunctiva was observed in all three tested animals, which was fully reversible within 48 or 72 hours.

 

CAS 106-70-7

An acute eye irritation study was performed with methyl hexanoate (CAS 106-70-7) according to the OECD guideline 405 (BASF 1992). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye of three Kleinrussen rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 1, 24, 48 and 72 hours after application. Mild redness of conjunctiva and lacrimation was observed in one out of three tested animals, which was fully reversible within 48 and 72 hours.

 

 

CAS 112-61-8

An acute eye irritation study was performed with methyl stearate (CAS No. 112-61-8) according to OECD Guideline 405 (Steiling, 1992). 0.1 mL (approx. 0.7 g) of the undiluted test substance was instilled into the right conjunctival sac of three Kleinrussen rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 24, 48 and 72 hours after application. Mild redness of conjunctiva was observed in two out of three tested animals, which was fully reversible within 48 and 72 hours.

 

CAS 91051-34-2

Fatty acids, palm-oil, methyl esters (CAS No. 91051-34-2) was tested in a primary dermal irritation study according to OECD Guideline 404 (Steiling, 1992). The shaved dorsal skin of four Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 15 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48, 72 hours as well as 7, 10 and 15 days after removal of the test patches. Moderate to severe erythema and oedema were observed after application of the test substance on rabbit skin for 4h under occlusive dressing. All skin reactions were fully reversible within 15 days.

 

CAS 68937-83-7

For fatty acids, C6-10, methyl esters (CAS No. 68937-83-7), an eye irritation study according to EU Method B.5 (Kästner, 1988) was performed under GLP conditions. 0.1 mL of the liquid undiluted test substance was instilled into the conjunctival sac of one eye of four Kleinrussen rabbits. The animals were observed for at least 48 hours. Eye irritation was scored according to the method of Draize 24 and 48 hours after application in all four animals. Additionally, in one animal the treated eye was scored 72 hours after application. No reactions were observed on the cornea and the iris of the treated animals. Slight to moderate conjunctival reactions were observed directly after instillation, which disappeared totally within 24 hours after application. All scores were zero at 24 and 48 hour readings in all four animals.

 

CAS 67762-26-9

Fatty acids, C14-18 and C16-18-unsatd., Methyl esters (CAS No. 67762-26-9) was tested for its eye irritation potential according to OECD Guideline 405 (Kästner, 1988). 0.1 mL of the liquid undiluted test substance was instilled into the conjunctival sac of one eye of four Kleinrussen rabbits. The animals were observed for 72 hours. Eye irritation was scored according to the method of Draize 1, 6, 24, 48 and 72 hours after application. Reactions on cornea and iris were not observed. The conjunctival reactions were slight (redness) and disappeared within 24 hours after application. All eye irritation scores were zero in all tested animals at 24, 48 and 72 hour reading time points.

 

Several acute eye irritation studies have been performed in rabbits in vivo. None of the tested fatty acid methyl esters showed an eye irritation potential. Therefore, based on a weight of evidence approach, no classification for eye irritation for all substances within the fatty acid methyl esters category is required.

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 Me category, data will be generated from a representative category member to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

The available data on irritation/corrosion of Fatty acids, C16-18, methyl esters is conclusive but not sufficient for classification.