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Administrative data

Description of key information

All available studies on the acute skin irritation potential of 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)

Additional information

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:

 

In a primary dermal irritation study, the skin irritation/corrosion potential of methyl laurate (CAS No. 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 No. 111-82-0) was tested according to D.O.T. Corrosivity, 49 CFR 173.240 (Hiles, 1981). 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.

 

A primary dermal irritation study was performed with methyl palmitate (CAS No. 112-39-0) according to OECD Guideline 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.

 

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.

 

Fatty acids, palm-oil, Me 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.

 

A primary dermal irritation study was performed with Fatty acids, C16-18 and C18-unsatd., Methyl esters (CAS No. 67762-38-3) according to OECD Guideline 404 (Steiling, 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 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.

 

A primary dermal irritation study was performed with methyl hexanoate (CAS No. 106-70-7) according to OECD Guideline 404 (Pittermann, 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 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.

 

Fatty acids, C6-10, Methyl esters (CAS No. 68937-83-7) was tested for its skin irritation potential according to OECD Guideline 404 (Kästner, 1988). The shaved dorsal skin of four Kleinrussen rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The animals were observed for 14 days. Skin reactions were assessed using the Draize scheme 24, 48, 72 hours as well as 8, 10 and 14 days after removal of the test substance. Well defined erythema and slight oedema was observed in all treated animals, which was fully reversible within 8-10 days. Based on the study results the test substance has to be classified as Xi, R38: Irritating to skin according to DSD.

 

A 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.

 

 

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:

 

A 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 70¿L 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.

 

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.

 

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.

 

 

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

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:

 

An acute eye irritation study was performed with methyl laurate (CAS No. 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 No. 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.

 

Methyl palmitate (CAS No. 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.

 

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.

 

Fatty acids, palm-oil, Me esters (CAS No. 91051-34-2) was tested for its eye irritation potential according to OECD Guideline 405 (Kästner, 1988). 0.1 mL of the undiluted test substance was instilled into the right conjunctival sac 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. Mild redness of conjunctiva was observed in one out of four tested animals, which was fully reversible within 48 hours. No other eye irritation was observed in any of the tested animals.

 

An acute eye irritation study was performed with methyl hexanoate (CAS No. 106-70-7) according to OECD Guideline 405 (Pittermann, 1992). 0.1 mL of the undiluted liquid 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.

 

An acute eye irritation study was performed with Fatty acids, C6-10, Methyl esters (CAS No. 68937-83-7) according to EU Method B.5 (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 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.

 

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.

 

Justification for classification or non-classification

According to DSD and CLP classification criteria for irritation/corrosion, no classification is required for skin and eye irritation for any of the members of the Category SCAE Methylester.