Registration Dossier

Administrative data

Description of key information

All available studies on skin and eye irritation showed no irritating potential of the category members.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for grouping of substances and read-across

The 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.

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, 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 Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

SKIN IRRITATION

Overview of skin irritation

CAS

Skin irritation

544-35-4 (b)

--

10233-13-3 (a)

Not irritating

110-27-0 (a)

Not irritating

142-91-6 (a)

Not irritating

68171-33-5 (a)

Not irritating

112-11-8 (a)

RA: 68171-33-5

RA: 112-10-7

112-10-7 (b)

Not irritating

91031-58-2 (a)

RA: 68171-33-5

RA: 112-10-7

RA:110-27-0

63393-93-1 (a)

Not irritating

123-95-5 (b)

Not irritating

67762-63-4 (b)

--

85408-76-0 (a)

RA: 163961-32-8

RA: 123-95-5

84988-74-9 (a)

RA: 163961-32-8

RA: 123-95-5

163961-32-8 (b)

Not irritating

646-13-9 (b)

--

85865-69-6 (a)

RA: 163961-32-8

RA: 123-95-5

84988-79-4 (a)

RA: 163961-32-8

RA: 123-95-5

6309-51-9 (a)

 

RA: 10233-13-3

RA: 34316-64-8

1365095-43-7 (a)

RA: 10233-13-3

RA: 34316-64-8

34316-64-8 (a)

Not irritating

2306-88-9 (a)

Not irritating

59587-44-9 (a)

RA: 92044-87-6

RA: 135800-37-2

20292-08-4 (a)

Not irritating

649747-80-8 (a)

RA: 20292-68-4

RA: 135800-37-2

135800-37-2 (b)

Not irritating

29806-73-3 (a)

Not irritating

22047-49-0 (a)

         Not irritating

92044-87-6 (a)

Not irritating

91031-48-0 (a)

RA: 29806-73-3

85049-37-2 (a)

RA: 29806-73-3

93572-14-6 (a)

RA: 29806-73-3

RA: 22047-49-0

RA: 26399-02-0

26399-02-0 (b)

Not irritating

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh, or not subject to the REACh Phase-in registration deadline of 31 May 2013, are indicated in normal font.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

Discussion

Skin irritation – Human Data

Several fatty acid C2-8 esters were tested in vivo on human skin. None of the tested fatty acid esters showed any relevant skin irritation potential on human skin:

Fatty acids, C8-16, 2-Ethylhexyl Esters (CAS 135800-37-2) was tested in an occlusive patch test with 20 human volunteers under GLP conditions (Krächter, 1990). The test substance (no data on purity) was applied at concentrations of 25%, 50% and 100% to the skin of 20 healthy volunteers under occlusive conditions for 24 h. Texapon N25 (1%), SDS (0.5%), Aqua dest. and Paraffin perliquid were used as controls. The volunteers were subsequently investigated for skin irritation for up to 72 h after exposition. The test substance caused no effects at concentrations of 25% and 50%. The undiluted substance mainly resulted in light and transient erythema. Only one well-defined erythema and 3 cases of oedema were detected. The positive controls resulted in slight to strong erythema and slight oedema formation (SDS and Texapon) in 6 and 17 volunteers, respectively, supporting the sensitivity and reliability of the test method. The test substance was considered to possess very good skin compatibility at 25% and 50% dilutions and good skin compatibility as undiluted substance.

A human 48-h patch test conducted with Octyl Octanoate (CAS 2306-88-9) is available (Frank, 2008). Patches containing 12.5, 25, 50 and 100% of the test substance (100% pure) were applied on the back of human volunteers for 48 hours and scored immediately after removal and 24 hours later. Observations of the site treated with 12.5 % remained negative. One subject exhibited barely-perceptible (+) erythema at the 25 and 50% test sites. Two subjects exhibited barely perceptible (+) erythema at the 100% test site. Under the conditions of this study, the test material did not indicate a clinically significant potential for dermal irritation at all dilutions tested.

 

Skin irritation – Animal Data

Several Fatty Acid C2-8 Esters were tested in vivo on rabbit skin. Some of the study results indicated no skin irritation potential at all, while other studies indicated a slight irritation potential on rabbit skin:

 

Skin irritation - Isopropyl ester 

CAS 10233-13-3

A primary dermal irritation study was performed with Isopropyl Laurate (CAS 10233-13-3) according to OECD Guideline 404 (Dufour, 1991). The shaved skin of three rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed according to Directive 67/548/CEE approx. 1, 24, 48 and 72 hours as well as 7 days after removal of the test substance.

The exposure period of 4 hours caused only slight oedema and erythema (score = 1, respectively) in one animal. The other two animals were free of any skin irritation. All treated skin sites appeared normal at the 72 hour observation.

 

CAS 110-27-0 

Seven primary dermal irritation studies are available to assess the skin irritation/corrosion potential of Isopropyl Myristate (CAS 110-27-0).

The first study was performed according to OECD Guideline 404 (Mulder, 1986) in female rabbits (New Zealand White). The shaved flank skin was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48 and 72 hours as well as 7 days after removal of the test substance.

The exposure period of 4 hours caused only very slight erythema (score = 1) in all animals that was fully reversible within 7 days. One rabbit showed slight oedema up to 48 h after application.

In a second study, also performed according to OECD Guideline 404 (Mulder, 1986), additional three female New Zealand White rabbits were treated with the undiluted test material for 4 hours. The animals showed slight to well-defined erythema (mean scores = 1.00, 1.33, and 2.00) and very slight oedema (mean scores = 0.67, 1.00, and 1.33) for the first three days after dosing. All skin reactions were fully reversible within 7 days.

The third study was performed in the same way (Mulder, 1986). The 4 h treatment resulted in slight to well-defined erythema (mean scores = 1.0, 1.7, and 0.0) and very slight oedema (1.0, 1.0, and 0.0). As in two of three animals erythema (score = 1) were still present after 7 days, the observation period was prolonged to 14 days. After 14 days effects had disappeared.

In an additional study that was performed according to a protocol equivalent to OECD Guideline 404, the undiluted test material (no data on purity) was applied to the abraded and intact skin of 6 New Zealand White rabbits (Lewis, 1978). The animals were exposed for 24 h under occlusive conditions and reading according to the Draize scheme was performed 24 and 72 h after application. Slight erythema and oedema (score = 1) were observed in all animals that were fully reversible within 72 h in 4/6 animals. As the effects were slight and the conditions harsher than compared to the current guideline, reversibility of all effects within a longer observation period was assumed. The scores for abraded skin were similar to the scores for intact skin. 

In a further study performed according to a protocol similar to OECD Guideline 404, 0.5 mL of the undiluted test material (no data on purity) were applied to the clipped skin of 3 rabbits under occlusive conditions for 24 h (Levenstein, 1973). The animals were observed for 48 h and reading time points were 24 and 48 h after patch removal. Formation of slight erythema (mean score = 0.5) was observed that was fully reversible within 48 h.

An additional study was performed according to a protocol similar to the OECD Guideline 404 (Dufour, 1991). Three New Zealand White rabbits were treated with the undiluted test material (no data on purity) for 4 h under occlusive conditions and were observed for 7 days. Only mild erythema (mean score = 0.33; fully reversible within 48 h) and oedema (mean score = 1.33; fully reversible within 7 days) were observed in one animal. The other animals did not show any reaction.

The last study was also performed according to a protocol similar to the OECD Guideline 404 (Patterson, 1971). 0.5 mL of the undiluted test material (no data on purity) was applied to the shaved and abraded skin of 6 Albino rabbits. The observation period was 48 h and scoring time points were 24 and 48 h after patch removal. No effects on shaved or abraded skin were observed.

In summary, the test material caused only very slight reactions on the skin, even under very harsh conditions; thus, it is not considered to be skin irritating.

 

CAS 142-91-6 

Isopropyl Palmitate (CAS 142-91-6) was tested for its skin irritation potential according to OECD Guideline 404 (Mulder, 1986). The shaved skin of three New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semi-occlusive conditions. The observation period was 14 days. Slight to well-defined erythema (mean scores = 1.0, 1.67, and 1.0) and very slight oedema (mean scores = 0.0, 0.67, and 0.0) occurred at readings up to 7 days after application. All changes were fully reversible within 14 days.

In a second study that was conducted according to a protocol similar to OECD Guideline 404, three Albino rabbits were treated at shaved, intact skin and abraded skin with the undiluted test material (no data on purity) under occlusive conditions (Patterson, 1971). The exposure period was not specified. The animals were observed for 7 days. Slight erythema formation was seen in all animals in the first 48 h. All effects were fully reversible within 72 h at intact and abraded skin, respectively.

An additional study on skin irritation performed according to OECD Guideline 404 is available (Dufour, 1991). Three New Zealand White rabbits were treated with 0.5 mL of the undiluted test substance (no data on purity) for 4 hours at intact and abraded skin under occlusive conditions. Slight erythema (mean scores = 1.0, 1.3, and 1.3) and slight oedema (mean scores = 0.67, 1.0, and 1.3) were observed that were fully reversible within the observation period of 7 days.

Taken together, only very slight reactions were caused by the test material that were fully reversible within 7 days; thus, the test material is not considered irritating to the skin.

 

CAS 68171-33-5

Two animal studies investigating the skin irritation of Isopropyl Isostearate are available (CAS 68171-33-5). In a primary dermal irritation study, the skin irritation/corrosion potential was tested according to OECD Guideline 404 under GLP conditions (Saboureau, 1989). The clipped skin of three New Zealand White rabbits was exposed to 0.5 mL unchanged test material (no data on purity) 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, and 72 hours after removal of the test substance. Very slight erythema was observed in all 3 animals at reading time point 1 h and persisted in one case until 24 h. The effect was fully reversible within 48 hours. Very slight oedema was seen in one animal at reading time point 1 h, which however was no more evident at 24 h.

The potential of cutaneous reactions to the application of product on the skin which was subsequently exposed to UV radiations was evaluated in an additional study in Albino guinea pigs under GLP conditions (Saboureau, 1989). 6 areas of 1 cm² of the clipped skin of 10 animals were treated with test item and then UVA irradiated, test item and then UVB irradiated, test item alone, positive control (8-methoxypsoralene) and then UVA irradiated, UVB irradiated alone, or UVA irradiated alone, respectively. The test item was applied at 0.02 mL/cm² 30 min before irradiation. 24 h after irradiation and/or treatment the cutaneous reactions were evaluated according to the Draize scoring system. No significant cutaneous reactions were observed at the level of the areas treated with the test substance, with or without UV radiations. For the positive control obvious skin reactions were seen. Thus, the test item showed no phototoxic potential under the experimental conditions in guinea pigs.

 

  

CAS 63393-93-1

One animal study investigating the skin irritation potential of Isopropyl Lanolate (CAS 63393-93-1) is available that was performed according to a protocol similar to OECD Guideline 405 (Paul, 1970). Six albino rabbits were treated with 0.5 mL of the undiluted test material for 24 hours under semi-occlusive conditions. The observation period was 72 hours and the effects were evaluated 24 and 72 hours after patch removal. Neither erythema nor oedema was observed in any animal.

 

Skin irritation - Butyl ester

CAS 123-95-5

Butyl stearate (CAS 123-95-5) was tested in a primary dermal irritation study in Albino rabbits (Wallace, 1976). The shaved skin of 6 animals was exposed to 0.5 mL of the unchanged test substance (no data on purity) for 24 hours under occlusive conditions. Treated skin sites were examined using the Draize scoring system 24 and 72 hours after application. Slight erythema (grade 1) was observed in two animals, which was fully reversible within 72 hours after application. No oedema occurred. Based on the study results, butyl stearate exerts no skin irritating potential.

CAS 163961-32-8

Fatty acids, C16-18 and C18-unsaturated, branched and linear, Butyl Esters (CAS 163961-32-8) was tested in an acute dermal irritation study in rabbits according to OECD Guideline 404 (Sanders, 2002). The shaved skin of three New Zealand White rabbits was exposed to 0.5 mL of the test substance (no data on purity) for 4 hours under semi-occlusive conditions. 24, 48 and 72 hours after patch removal the test sites were examined for evidence of primary irritation and scored according to Draize. Slight erythema and oedema (grade 1, respectively) occurred in all treated skin sites, which were all fully reversible within 48 or 72 hours. Based on the study results, the test substance shows no skin irritating potential.

 

Skin irritation - Hexyl ester

CAS 34316-64-8

An acute skin irritation study was performed with Hexyl Laurate (CAS 34316-64-8) according to a protocol similar to OECD Guideline 404 (Masson, 1987). The intact and incised skin of 6 male New Zealand rabbits was treated with 0.5 mL of the test material (no data on purity) for 24 hours under occlusive conditions. The animals were observed for 72 h and scoring according to the Draize scoring system was performed 24 and 72 h after patch removal. Slight to moderate erythema (mean scores = 1.0, 1.67, 1.67, 0.67, 1.0, and 2.0) as well as very slight oedema (mean scores = 0.0, 0.67, 0.0, 0.0, 0.0, and 0.33) were observed assuming the 48-h reading to be the same as the 24-h reading. Full reversibility within the observation period was observed only for one animal. The results for incised skin were not taken into account for evaluation but were comparable. Due to the major deviation from the actual guideline, which requires semi-occlusive conditions, only 4 h exposure and an observation period of 14 days, the test material is not considered skin irritating as reversibility of the effects within an adequate observation period is assumed.

 

Skin irritation - Ethylhexyl ester

CAS 20292-08-4

An acute dermal irritation study performed according to a protocol similar to OECD Guideline 404 to evaluate the skin irritation potential of 2-Ethylhexyl Laurate (CAS 20292-08-4) is available (Bouffechoux, 1996). Only basic data on the test method were given. Three New Zealand rabbits were dermally treated with the undiluted test material (no data on purity) and were then observed for 7 days. Evaluation was performed according to Draize 1, 24, 48, 72 hours, and 7 days after application. Slight to moderate erythema was observed in all animals (mean scores = 1.0, 1.33, and 2.0) that was fully reversible within 72 h, 72 h, and 7 days, respectively. No oedema formation was observed in any animals. Thus, the test substance is not considered skin irritating.  

 

CAS 29806-73-3

Three studies performed with 2-Ethylhexyl Palmitate (CAS 29806-73-3) to assess the skin irritating potential are available.

An acute dermal irritation test was performed according to OECD Guideline 404 under GLP conditions (Guest, 1990). The shaved skin of three New Zealand White rabbits was exposed to 0.5 mL of the unchanged test substance (no data on purity) for 4 hours under semi-occlusive conditions. Then, the test substance was gently wiped off with cotton wool soaked in diethyl ether. The treated skin sites were examined according to the Draize scoring system 24, 48 and 72 hours after application. Only very slight erythema (mean scores = 0.67, 0.33, and 0.67) occurred, which were fully reversible within 48 to 72 hours.

In a second acute dermal irritation study performed according to a protocol similar to OECD Guideline 404, three albino rabbits were treated with 0.5 mL of the unchanged test material (no data on purity) for 24 hours under occlusive conditions at shaved intact and abraded skin sites (Green, 1972). Scoring according to Draize was performed 24 and 72 h after application. No irritation reaction was observed even when the test substance was applied on abraded skin sites (worst case exposure scenario).

A further study was performed according to a protocol similar to OECD Guideline 404 (Planchette, 1985). Six New Zealand White rabbits were treated with 0.5 mL of the unchanged test substance (no data on purity) for 24 h under occlusive conditions. The animals were observed for 72 hours and scoring according to Draize was performed 24 and 72 h after application. No skin reaction was observed in any animal at any time point of the study.

In summary, based on the study results the test substance is not considered skin irritating.

 

CAS 22047-49-0

One acute dermal irritation study performed similar to OECD Guideline 404 to evaluate the skin irritation potential of 2-Ethylhexyl Stearate (CAS 22047-49-0) is available (Masson, 1985). Six New Zealand rabbits were treated with 0.5 mL of the unchanged test substance (no data on purity) for 24 h under occlusive conditions. The animals were observed for 72 hours and scoring according to Draize was performed 24 and 72 h after application. Slight to moderate erythema was observed in all animals (mean scores = 1.33, 1.67, 2.0, 0.67, 0.67, and 2.0) and slight oedema formation (mean score = 0.33) was only seen in one animal. The mean values were calculated assuming the 48-h reading to be the same as the 24-h reading. 3/6 animals were without any effects 72 h after application whereas in the remaining three rabbits the signs for irritation were still present. As the effects were slight and the deviations from the current guideline might lead to an overestimation of the effects (24 h instead of 4 h treatment, occlusive instead of semi-occlusive), reversibility within an adequate observation period up to 14 days is assumed. Therefore, the test substance is not considered irritating to the skin.

 

CAS 92044-87-6

The skin irritation/corrosion potential of Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) was tested in a primary dermal irritation study according to OECD Guideline 404 under GLP conditions (Weterings 1987). The clipped skin of three New Zealand White rabbits was exposed to 0.5 mL unchanged test material (approx. 100% pure) for 4 hours under semi-occlusive conditions. Then, test substance residues were wiped off with a dry and a water-moistened tissue. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scheme 45 min, 24, 48, 72 hours, and 7 days after patch removal. Slight erythema (mean scores = 1.0, 1.0, and 0.67) and slight oedema (mean scores = 1.0, 0.67, and 0.67) were observed in all animals. All effects were fully reversible within 72 h to 7 days. Thus, the test substance was is not irritating in this study.

In a second study performed according to a protocol similar to OECD Guideline 404 six New Zealand rabbits were treated with 0.5 mL of the test substance (no data on purity) for 24 h under occlusive conditions on intact and incised skin (Masson, 1985). The animals were observed for 72 h and scoring according to Draize was performed 24 and 72 h after patch removal. No reactions were observed in any animals and thus, the test substance is not considered irritating.

 

CAS 26399-02-0

The skin irritation/corrosion potential of 2-Ethylhexyl Oleate (CAS 26399-02-0) was tested in a primary dermal irritation study according to OECD Guideline 404 (Dufour, 1991). The skin of three New Zealand White rabbits was exposed to 0.5 mL unchanged test material (no data on purity) for 4 hours under occlusive conditions. The rabbits were observed for 72 hours. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48 and 72 hours after removal of the test substance. The exposure period of 4 hours caused only very slight oedema and erythema in one rabbit (mean scores = 0.33, respectively). All treated skin sites appeared normal at the 48 hour observation. Therefore, the test substance is not considered irritating.

 

CAS 135800-37-2

Another acute skin irritation study was performed with Fatty acids, C8-16, 2-Ethylhexyl Esters (CAS 135800-37-2) according to OECD Guideline 404 (Steiling, 1990). The shaved skin of four adult Kleinrussen rabbits was exposed to 0.5 mL test substance (no data on purity) for 4 hours under occlusive conditions. The animals were observed for 7 days. Skin examinations according to Draize revealed only slight erythema (mean scores = 1.33, 0.67, 0.67, and 0.33) in four animals which was fully reversible within 7 days and slight oedema (mean score = 0.33) in one animal which was fully reversible in 48 hours. Based on this study result, the test substance has no skin irritating potential.

 

Skin irritation - further ester

CAS 2306-88-9

An acute skin irritation study was performed with Octyl Octanoate (CAS 2306-88-9) according to a protocol similar to OECD Guideline 404 (Potokar, 1981). The skin of two New Zealand rabbits was treated with 0.5 mL of 1% and 5% of the test material (no data on purity) for 4 hours under occlusive conditions. After 4 hours, test substance residues were removed with distilled water. The animals were observed for 48 hours. Skin examinations according to Draize were performed directly after patch removal and after 24 and 48 hours. The treatment did not cause any effect. Based on the result of this study, the test material was not considered skin irritating; however, only low concentrations of the test substance instead of 100% were tested.

 

Conclusion for skin irritation

Based on the results of the available animal studies as well as according to the results on human skin, none of the substances within the fatty acid C2-8 ester category is considered skin irritating. Therefore, based on a weight of evidence approach, no classification for skin irritation for all substances within the fatty acid C2-8 esters category is required.

EYE IRRITATION

Overview of eye irritation

CAS

Eye irritation

544-35-4 (b)

Not irritating

10233-13-3 (a)

RA: 11027-0

110-27-0 (a)

Not irritating

142-91-6 (a)

Not irritating

68171-33-5 (a)

Not irritating

112-11-8 (a)

RA: 68171-33-5

91031-58-2 (a)

RA: 68171-33-5

RA: 142-91-6

RA:110-27-0

63393-93-1 (a)

Not irritating

123-95-5 (b)

Not irritating

67762-63-4 (b)

--

84988-74-9 (a)

RA: 163961-32-8

RA: 123-95-5

163961-32-8 (b)

Not irritating

646-13-9 (b)

--

85865-69-6 (a)

RA: 163961-32-8

RA: 123-95-5

84988-79-4 (a)

RA: 163961-32-8

RA: 123-95-5

6309-51-9 (a)

 

RA: 110-27-0

RA: 20292-08-4

1365095-43-7 (a)

RA: 110-27-0

RA: 20292-08-4

34316-64-8 (a)

RA: 20292-08-4

RA: 163961-32-8

RA: 110-27-0

2306-88-9 (a)

RA: 20292-08-4

RA: 92044-87-6

59587-44-9 (a)

RA: 92044-87-6

20292-08-4 (a)

Not irritating

649747-80-8 (a)

RA: 20292-08-4

RA: 92044-87-6

135800-37-2 (b)

--

29806-73-3 (a)

Not irritating

22047-49-0 (a)

        RA: 91031-48-0

92044-87-6 (a)

Not irritating

91031-48-0 (a)

Not irritating

85049-37-2 (a)

RA: 91031-48-0

93572-14-6 (a)

RA: 29806-73-3

RA: 91031-48-0

26399-02-0 (b)

--

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(b) Substances that are either already registered under REACh, or not subject to the REACh Phase-in registration deadline of 31 May 2013, are indicated in normal font.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

Eye irritation - Isopropyl ester

CAS 110-27-0

Three animal studies investigating the eye irritation of Isopropyl Myristate (CAS 110-27-0) are available. An acute eye irritation study was performed according to a protocol similar to OECD Guideline 405 with 3 New Zealand White rabbits (Palanker, 1977). One eye of the rabbits was exposed to 0.1 mL of the undiluted test substance (no data on purity) and scored for eye reactions. The animals were observed for 7 days and scoring was performed 24, 48 and 72 h and 4 and 7 days after application. Only conjunctival redness (grade 1) was observed in two animals at the 24 h reading that was fully reversible within 48 h. No effects on conjunctival swelling, iris, or cornea were observed.

In an additional study, performed according to a protocol similar to the OECD Guideline 405, three albino rabbits were treated with 0.1 mL of the undiluted test material (no data on purity) (Croda Europe, 1973). The observation period was 7 days and no effects were observed at any reading time point.

A further study was conducted in a similar way with an observation period of only 3 days (Wallace, 1975). No ocular reactions were observed except of slight conjunctival redness at 24 h in 4/6 animals that was fully reversible within 48 h.

In summary, it is concluded that the test material has no potential for eye irritation.

 

CAS 142-91-6

Isopropyl Palmitate (CAS 142-91-6) was tested for its acute eye irritation potential in a study performed equivalent to OECD Guideline 405 (Prince, 1971). 0.1 mL of the unchanged test substance (no data on purity) was instilled into one eye of 6 rabbits. 1, 24, 48 and 72 hours later, treated eyes were examined for ocular lesions according to Draize. After a single instillation the test substance caused mild irritations (conjunctival swelling and redness) to rabbit eyes that were fully reversible within 72 hours.

CAS 68171-33-5

Isopropyl Stearate (CAS 68171-33-5) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 under GLP conditions (Saboureau, 1989). The undiluted test material (no data on purity) was applied into the conjunctival sac of three New Zealand White rabbits. The animals were observed for 72 hours and reactions were assessed 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. Slight conjunctivae redness with slight chemosis and lacrimation graded 2 to 3 were seen in all 3 animals at reading time point 1 h. Slight redness persisted in 2 cases until reading time point 24 h. All effects were fully reversible within 48 hours. Thus, the test material is not considered irritating to the eyes in this study. 

 

CAS 63393-93-1

Two animal studies investigating the eye irritating potential of Isopropyl Lanolate (CAS 63393-93-1) are available. The first study was performed according to a protocol similar to OECD 405 (CTFA, 1977). 0.1 mL of the test material (no data on purity) was instilled into the conjunctival sac of 9 New Zealand White rabbits and rinsed after 30 seconds in 3 of them. The animals were observed for 7 days and reading was performed 24, 48, 72 hours, 4 and 7 days after treatment according to the Draize scoring system. Slight conjunctivae redness graded 1 was seen in 1/6 animals (without washing) at reading time points 24 and 48 h. The conjunctival effect was fully reversible within 72 hours. Slight chemosis graded 1 was observed in 1/6 animal at reading time point 24 h and was fully reversible within 48 hours. Slight conjunctival redness graded 1 was seen in 1/3 animals (with washing) at reading time point 24 hours and was fully reversible within 48 hours.

In an additional study performed according to a protocol similar to OECD Guideline 405 (Paul, 1970), 9 Albino rabbits were treated with 0.1 mL of the undiluted test substance (no data on purity). It was instilled into the conjunctival sac of each animal and the eyes of 3 rabbits were rinsed 2 seconds after instillation and the eyes of another 3 rabbits after 4 seconds. The eyes of the remaining 3 rabbits were not rinsed. All animals were observed for 7 days and scoring was performed according to the Draize scoring system. No effect was seen in any of the animals. Thus, the test material is not considered irritating to the eyes in this study.

 

Eye irritation - Butyl ester

CAS 163961-32-8

Fatty acids, C16-18 and C18-unsaturated, branched and linear, Butyl esters (CAS# 163961-32-8) was tested in an acute eye irritation study according to OECD Guideline 405 (Sanders, 2002). 0.1 mL of the unchanged liquid test substance (no data on purity) was instilled to the eye of three New Zealand White rabbits. Examination of treated eyes 1, 24, 48 and 72 hours after instillation according to Draize revealed minimal to moderate conjunctival irritation in all treated eyes one hour after treatment with minimal conjunctival irritation in two treated eyes at the 24-hour observation. One treated eye appeared normal at the 24-hour observation and the two remaining treated eyes appeared normal at the 48-hour observation. One animal showed slight discharge at 24 hours.

 

CAS 123-95-5

A primary eye irritation study was performed with Butyl Stearate (CAS 123-95-5). 0.1 mL of the unchanged test substance (no data on purity) was instilled to the eye of six albino rabbits (Wallace, 1976). Examination of the treated eyes 1, 24, 48, 72 hours, and 7 days after instillation revealed only slight conjunctival irritating effects (grade 1) in 5/6 animals, which were fully reversible within 48 or 72 hours. Based on the study results, butyl stearate had no eye irritation potential.

 

Eye irritation - Ethylhexyl ester

CAS 20292-08-4

An acute eye irritation test performed according to OECD Guideline 405 to evaluate the eye irritation potential of 2-Ethylhexyl Laurate (CAS 20292-08-4) is available (Bouffechoux, 1996). The test substance (no data on purity) was instilled in the conjunctival sac of three New Zealand rabbits. The animals were observed for 7 days and scoring of iris, cornea and conjunctivae according to Draize was performed 1, 24, 48, 72 hours and 7 days after application. Slight conjunctival effects (mean score = 0.33 in all animals) were observed up to 24 h that were fully reversible within 48 h. No information is given if these effects were reddening or swelling of the conjunctivae as only a summary of the results is available. However, based on the results of the study the test substance is not considered eye irritating and classification is not warranted.  

CAS 29806-73-3

Four studies are available to evaluate the eye irritation potential of 2-Ethylhexyl Palmitate (CAS 29806-73-3).

An acute eye irritation study was performed according to OECD Guideline 405 under GLP conditions (Guest, 1990). 0.1 mL of the unchanged test substance (no data on purity) was instilled to the right eye of three New Zealand White rabbits. The untreated left eye served as control. Examination of the treated eyes 24, 48 and 72 hours after instillation revealed no ocular changes.

In a second study performed according to a protocol similar to OECD Guideline 405, 0.1 mL of the test substance (no data on purity) was instilled in one eye of six New Zealand White rabbits (Sugar, 1980). The animals were observed for 72 hours and scoring according to Draize was performed 24, 48, and 72 hours after instillation. Slight effects were observed on conjunctivae (redness and swelling) and in one animal on iris (grade 1 at 24 h). The mean scores (24, 48, and 72 h) for conjunctivae redness were 0.67, 0.67, 0.33, 0.67, 1.0, and 1.33 and for conjunctivae swelling 0.33, 0.33, 0.67, 0.67, 0.33, and 0.33. All effects were fully reversible within 72 h except in one animal (conjunctivae redness grade 1 at 72 h). However, full reversibility in case of a prolonged and thus adequate observation period is assumed. Therefore, the test substance is not considered eye irritating in this study.

Another eye irritation study was performed according to a protocol similar to OECD Guideline 405 (Sugar, 1981). 0.1 mL of the undiluted test substance (no data on purity) was instilled in the eyes of 6 New Zealand White rabbits. The animals were observed for 72 hours and scoring was performed 24, 48 and 72 hours after application according to the Draize scoring system. Slight effects on conjunctivae redness (mean scores: 0.67, 0.67, 1.00, 0.33, 0.67, and 1.0) and swelling (mean scores: 0.33, 0.67, 0.33, 0.0, 0.33, and 0.0) were observed that were fully reversible within 72 and 48 hours, respectively. Hence, in this study the test substance caused no irritation in the rabbit eye.

A further study on the eye irritation potential of the test substance is available (Green, 1972). It was performed according to a protocol similar to OECD Guideline 405. 0.1 mL of the unchanged test substance (no data on purity) was instilled in one eye of three albino rabbits. The animals were observed for ocular effects for 7 days. Scoring according to the Draize scheme was performed 1 hour after application and daily afterwards. Slight iris and conjunctivae effects were observed in all 3 animals one hour after instillation. These effects were fully reversible within 24 hours. 

Based on the results of all four studies, the test substance is not considered eye irritating.

CAS 91031-48-0

Fatty acids, C16-18, 2-Ethylhexyl Esters (CAS 91031-48-0) was examined for its eye irritation potential in a study performed equivalent to OECD Guideline 405 (Potokar, 1978). 0.05 mL undiluted test substance (no data on purity) was instilled into the right eye of 2 rabbits. 2, 6 and 24 hours after instillation examination of the treated eyes revealed no ocular lesions. Thus, based on the study results, the test substance showed no eye irritating potential.

 

CAS 92044-87-6

One study with Fatty acids, coco, 2-Ethylhexyl Esters (CAS 92044-87-6) for the assessment of the acute eye irritation/corrosion potential is available (Weterings, 1987). The study was performed according to OECD Guideline 405 under GLP conditions. 0.1 mL of the test substance (approx. 100% pure) was instilled into the eyes of three female New Zealand White rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. 2/3 animals showed only slight swelling of the blood-vessels in the conjunctivae 1 hour after instillation. The effects were fully reversible within 24 hours. The fluorescein analysis 24 hours after instillation did not reveal any epithelial damage. Based on the results of the study, the test substance is not considered irritating to the eyes.

Eye irritation - further ester

CAS 2306-88-9

One animal study performed according to a protocol similar to OECD Guideline 405 with Octyl Octanoate (CAS 2306-88-9) is available (Potokar, 1981). 0.1 mL of 1% test substance (no data on purity) was instilled in the eyes of two New Zealand rabbits. The other eye of each animal served as control. Scoring according to Draize was performed 2, 6, and 24 hours after instillation. No effect was observed. Based on the result of this study, the test substance did not cause eye irritation in rabbits; however, it was only tested as a 1% solution instead of the undiluted substance.

 

Conclusion for eye irritation

Several acute eye irritation studies have been performed in rabbits in vivo. None of the tested fatty acid esters showed an eye irritation potential. Therefore, based on a weight of evidence approach, no classification for eye irritation for all substance s within the fatty acid C2-C8 esters category is required.

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR.

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.

Therefore, based on the group concept, the available data on skin and eye irritation 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.