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 Glycerides category covers aliphatic (fatty) acid esters of glycerol. The category contains both well-defined and UVCB substances with aliphatic acid carbon chain lengths of C2 (acetate) and C7-C22, which are mostly linear saturated and even numbered. Some of the substances in the category contain unsaturated fatty acids (e.g. oleic acid in 2,3-dihydroxypropyl oleate, CAS 111-03-5 or general fatty acids C16-22 (even) unsaturated in Glycerides, C14-18 and C16-22-unsatd., mono- and di-, CAS 91744-43-7). Some category members contain branched fatty acids. Branching is mostly methyl groups (e.g. isooctadecanoic acid, monoester with glycerol, CAS 66085-00-5 or 1,2,3-propanetriyl triisooctadecanoate, CAS 26942-95-0). In one category member the branching cannot be precisely located (Glycerides, C16-18 and C18-unsatd., branched and linear mono-, di- and tri, ELINCS 460-300-6). Hydroxylated fatty acids are present in three substances (Castor oil, CAS 8001-79-4; castor oil hydrogenated, CAS 8001-78-3 and 2,3-dihydroxypropyl 12-hydroxyoctadecanoate, CAS 6284-43-1). Hydroxylation occurs on C12 of stearic acid in all these substances. Acetylated chains are present in the last part of the category, comprising fatty acids from C8 to C18 (even) and also C18 unsaturated, additionally a C18 acetylated fatty acid is present with the acetic acid located in C12 position (e.g. Glycerides, castor oil mono-, hydrogenated acetates / 12-acetoxy-octadecanoic acid, 2,3-diacetoxy, CAS 736150-63-3). All glycerides build mono-, di- and tri-esters in variable proportions.

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 Section 13) and within Chapter 5.1 of the CSR.

 

Overview of Irritation / corrosion

CAS

Skin Irritation

Eye Irritation

26402-26-6 (b)

Experimental result:
not irritating

--

142-18-7 (a)

WoE:
RA: CAS 538-24-9
RA: CAS 67701-26-2
RA: CAS 97593-30-1 (C12)

Experimental result:
not irritating

25496-72-4

Experimental result:
not irritating

Experimental result:
not irritating

66085-00-5

Experimental result:
not irritating

Experimental result:
not irritating

6284-43-1

WoE:
RA: CAS 736150-63-3
RA: CAS 91845-19-1

WoE:
RA: CAS 736150-63-3
RA: CAS 91845-19-1

620-67-7

WoE:
Experimental result:
not irritating

Experimental result:
not irritating

538-24-9

Experimental result:
not irritating

Experimental result:
not irritating

122-32-7

RA: CAS 25496-72-4

RA: CAS 25496-72-4

555-43-1

Experimental result:
not irritating

Experimental result:
not irritating

26942-95-0

Experimental result:
not irritating

Experimental result:
not irritating

91052-47-0

WoE:
RA: CAS 31566-31-1
RA: CAS 85251-77-0

RA: CAS 85251-77-0

91744-09-1

WoE:
RA: CAS 31566-31-1
RA: CAS 85251-77-0
RA: CAS 91744-13-7

WoE:
RA: CAS 85251-77-0
RA: CAS 91744-13-7

85536-07-8

WoE:
RA: CAS 73398-61-5
RA: CAS 65381-09-1
RA: CAS 26402-26-6

WoE:
RA: CAS 73398-61-5
RA: CAS 65381-09-1

91052-49-2

RA: CAS 67701-26-2

RA: CAS 67701-26-2

67701-33-1

Experimental result:
not irritating
RA: CAS 85251-77-0

Experimental result:
not irritating
RA: CAS 85251-77-0

67784-87-6

WoE:
Experimental result:
not irritating
RA: CAS 85251-77-0

RA: CAS 85251-77-0

91845-19-1

Experimental result:
not irritating

Experimental result:
not irritating

97358-80-0

WoE:
RA: CAS 26942-95-0
RA: CAS 66085-00-5

WoE:
RA: CAS 26942-95-0
RA: CAS 66085-00-5

91744-13-7

Experimental result:
not irritating

Experimental result:
not irritating

31566-31-1

WoE:
Experimental result:
not irritating (75%)
RA: CAS 85251-77-0

RA: CAS 85251-77-0

85251-77-0

Experimental result:
not irritating

Experimental result:
not irritating

91052-28-7

RA: CAS 91744-13-7

RA: CAS 91744-13-7

91052-54-9

Experimental result:
not irritating

Experimental result:
not irritating

91744-20-6

RA: CAS 91744-13-7

RA: CAS 91744-13-7

97722-02-6

RA: CAS 91744-13-7

RA: CAS 91744-13-7

77538-19-3

Experimental result:
not irritating

Experimental result:
not irritating

91744-28-4

RA: CAS 67701-26-2

RA: CAS 67701-26-2

68606-18-8

WoE:
RA: CAS 67701-26-2
RA: CAS 73398-61-5
RA: CAS 85536-06-7

WoE:
RA: CAS 67701-26-2
RA: CAS 85536-06-7
RA: CAS 73398-61-5

65381-09-1

Experimental result:
not irritating

Experimental result:
not irritating

73398-61-5

Experimental result:
not irritating

Experimental result:
not irritating

85536-06-7

Experimental result:
not irritating

WoE:
RA: CAS 67701-26-2
RA: CAS 620-67-7
RA: CAS 555-43-1
RA: CAS 73398-61-5

67701-26-2

Experimental result:
not irritating

Experimental result:
not irritating

8001-78-3

RA: CAS 67701-26-2

RA: CAS 67701-26-2
Experimental result:
not irritating (5%)

97593-30-1 (C10 )

RA: CAS 97593-30-1 (C12)

RA: CAS 97593-30-1 (C12)

97593-30-1 (C12)

Experimental result:
not irritating

Experimental result:
not irritating

93572-32-8

WoE:
RA: CAS 85251-77-0
RA: CAS 736150-63-3

WoE:
RA: CAS 85251-77-0
RA: CAS 736150-63-3

91052-13-0

WoE:
RA: CAS 67701-33-1
RA: CAS 67701-26-2
RA: CAS 91744-13-7

WoE:
RA: CAS 67701-33-1
RA: CAS 67701-26-2
RA: CAS 91744-13-7

736150-63-3

Experimental result:
not irritating

Experimental result:
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.

(c) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco )toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

(d) Assessment of toxicological properties is conducted also taking into account available data on mixtures of synthetic and/or naturally occurring glycerides (e.g. vegetable oils), which cannot be identified by a (single) CAS/EC number. The test materials short-, medium- and long-chain triglycerides (SCT, MCT, LCT) and their combinations (e.g. MLCT, SALATRIM – a SLCT) comprise triesters of glycerol with fatty acid chain lengths of C2 and C4 (short-chain), C8 and C10 (medium-chain) and C18 saturated/unsaturated (long-chain). The substance “mixture of mono-, di-, and triglycerides of lauric acid” comprises mono-, di and triesters of glycerol with dodecanoic acid (C12). The substance “Modified triglyceride” contains main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol, comprising triesters of glycerol with hexadecanoic (C16) and (9Z)-Octadec-9-enoic acid (C18:1). Available data on identity and composition of the individual test material for a given study is provided in the technical dossier.

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 "--".

 

Skin irritation

CAS No. 26402-26-6

The skin irritation potential of octanoic acid, monoester with glycerol was investigated in a GLP-conform study performed according to OECD guideline 404 (Guest, 1989). The test substance was diluted with arachis oil B.P. to a concentration of 20% (w/v) and 0.5 mL of this solution were applied for 4 h to the shaved skin of three New Zealand White rabbits (1 male and 2 females) under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48, 72 h and 7 days after removal of the dressing. Very slight erythema was noted in all treated animals 1 h after treatment and in 2/3 animals at the 24 and 48 h reading time point. In 1/3 animals, very slight erythema was still persistent up to the 72 h observation time point, but was fully reversible within 7 days. No edema formation was noted in treated animals during the study period. However, desquamation was commonly observed among these animals. No signs of systemic toxicity were seen. The individual mean erythema scores over 24, 48 and 72 h were 0.67/0/1. Mean edema scores over the 24, 48 and 72 h reading time points were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 142-18-7

A study investigating the skin irritation potential of 2,3-dihydroxypropyl laurate was performed in New Zealand White rabbits according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (Sterner, 1977). A 10% aqueous solution of the test substance (0.5 mL) was applied for 24 h to the shaved or abraded skin of 6 animals under occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24 and 72 h after removal of the dressing. 24 h post-application, very slight erythema was observed in 3/6 animals and very slight edema was noted in 2/6 animals. These effects were fully reversible within 72 h. No further local or systemic effects were reported. The mean erythema and edema scores out of all 6 animals over 24, 48 and 72 h were 0.3 and 0.2, respectively. Therefore, the test substance is considered as not irritating to the skin.

In a further study performed according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics", 0.5 g of the neat test substance moistened with alcohol was applied to the shaved and abraded skin of 6 New Zealand White rabbits for a period of 24 h under occlusive conditions (Sterner, 1977)). No effects on skin were observed at the 24 h reading time point. In contrast, very slight and well-defined erythema was observed in 2/6 and 4/6 animals, respectively, at the72 h reading time point. At the same time point, very slight and slight edema was noted in 1/6 and 5/6 animals, respectively. The mean erythema and edema scores over 24, 48 and 72 h were 1.1 and 1.2 for all 6 animals. Since the observation period was only 72 h, no conclusion could be drawn on the reversibility of the effects. Thus, this study was not considered as reliable and therefore not further taken into account for hazard assessment.

CAS No. 25496-72-4

The skin irritation potential of Glycerol monooleate was investigated in New Zealand albino rabbits (Rzucidlo, 1967). In this study, the undiluted test substance (0.5 g) was applied for 24 h to the shaved or abraded skin of six female rabbits. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24 and 72 h after removal of the dressing. No reactions were observed on shaved or abraded skin at any reading time point. During the study period, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over 24 and 72 h were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 66085-00-5

A skin irritation study was conducted with Glycerol monoisostearate according to OECD guideline 404 and in compliance with GLP (Saboureau, 1989). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 3 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 5 days after removal of the dressing. Slight erythema was observed in 2/3 animals at 1, 24 and 48 h after patch removal, which was fully reversible within 72 h. In one of these animals, very slight edema was observed at the 1 h reading only. Well-defined erythema was observed in the third animal at 1, 24 and 48 h post-application, which decreased to slight erythema at 72 h reading and was fully reversible within the 5-day observation period. In the same animal, very slight edema was seen at the 1, 24 and 48 h reading time points, which was fully reversible within 72 h. Slight changes in cutaneous structure were also observed, which were only slowly reversible. During the study period, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over 24, 48 and 72 h were 0.7/1.7/0.7 and 0/0.7/0 for the 3 individual animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 620-67-7

The skin irritation potential of Propane-1,2,3-triyl trisheptanoate was investigated in a GLP-conform study according to OECD guideline 404 (Mürmann, 1993). The shaved skin of 6 male Small White Russian, Chbb:HM rabbits were exposed for 4 h to 0.5 mL of the undiluted test substance under semiocclusive conditions. Skin reactions were assessed 30-60 min, 24, 48 and 72 h as well as 6, 8, 10 and 14 days after removal of the test substance. Well-defined erythema and very slight to well-defined edema were observed in all animals 30-60 min after patch removal. One animal showed moderate to severe erythema and severe edema with brown discolouration and dryness of the skin after 24-72 h. Sanguineous lacerations and scaling were also observed on the skin. At these time points, 4 animals showed no increase in the severity of the described signs of irritation. Moderate redness of the skin was observed in one animal after 72 h. After 72 h, this animal also showed dry skin and severe extensive subcutaneous haemorrhage. After 6 days, scaling was observed in all animals, and after 10 to 14 days, all animals were free of any skin reactions and abnormalities. No signs of systemic toxicity were seen. The mean erythema and edema scores out of all 6 animals after 24, 48 and 72 h were 2.22 and 1.94, respectively. According to Directive 67/548/EEC, the test substance is considered to be irritating to the skin. However, no classification as skin irritant is required according to Regulation (EC) 1272/2008.

There is evidence from another skin irritation study according to OECD guideline 404 to show that the test substance is not skin irritating (Dufour, 1993). In this study, the shaved skin of 3 male New Zealand white rabbits was exposed to 0.5 mL of the undiluted test substance for a period of 4 h. The untreated site of the animals served as control. Scoring of skin reactions was performed 1, 24, 48 and 72 h and 4, 5, 6 and 7 days after dressing removal. At the 1 h reading, very slight and slight erythema were noted in 1/3 and 2/3 animals, respectively. At the same time point, very slight edema was also observed in 1/3 animals, which persisted up to the 5 day reading time point and was fully reversible 6 days after dressing removal. In 2/3 animals, the very slight erythema were still visible up to 5 days after dressing removal and then fully reversible at the 6 day reading time point. In the other animals, very slight erythema was only seen after 24 h, but not at any later reading time point. The individual mean erythema and edema scores over the 24, 48 and 72 h reading time points were 1/0.3/1.3 and 0/0/1 for the 3 animals, respectively. Thus, the test substance was not irritating to the skin.

Furthermore, a human patch test was performed in 15 male and 35 female volunteers to assess the skin irritating potential of Propane-1,2,3-triyl trisheptanoate in humans (Tronnier, 2003). The undiluted test substance was applied once at 2 mg test substance/cm² to healthy skin on the back area of the test subjects using a commercial test patch for 48 h. After patch removal, skin reactions were evaluated immediately (48 h post-application) and 24 h later (72 h post-application). No primary skin irritation was observed 48 or 72 h after test substance application. Furthermore, no skin reactions resulting from an existing sensitisation were induced in this test. Based on these results, the test substance was not considered to be a skin irritant in humans.

CAS 538-24-9

The skin irritation potential of Glycerol trilaurate was investigated in a study performed according to OECD 404 (Dufour, 1988). The test substance was applied to the skin of 3 New Zealand White rabbits and the scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. Very slight erythema was observed in all 3 animals 1 h after patch removal, which were fully reversible at the 24 h reading time point. No further skin reactions were noted in any animal at any other reading time point. No further local or systemic effects were reported. The mean erythema and edema scores after over the 24, 48 and 72 h reading time points were 0 for the 3 animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 555-43-1

The skin irritation potential of Glycerol tristearate was investigated in a GLP-conform study according to OECD guideline 404 (Krueger, 1998). The undiluted test substance (0.5 g) was moistened with demineralised water and applied for 4 h to the shaved skin of 3 male White New Zealand albino rabbits under occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 30-60 min, 24, 48 and 72 h after removal of the dressing. No skin reactions were observed in the animals at any reading time point. During the study period, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over 24, 48 and 72 h were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 26942-95-0

The skin irritation potential of 1,2,3-propanetriyl triisooctadecanoate was investigated in a GLP-conform study performed according to OECD 404 (Saboureau, 1988). The test substance (0.5 mL) was applied for 4 h to the shaved skin of 3 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 5, 6, 7 and 8 days after removal of the dressing. Very slight erythema was observed in 2/3 animals 1 h after patch removal, which persisted until Day 5 and 6, respectively. No edema was noted in any animal at any reading time point. Very slight loss of skin elasticity and dryness were observed. No signs of systemic toxicity were seen during the study. The individual mean erythema scores over the 24, 48 and 72 h reading time points were 1/1/0, edema scores were 0 for the 3 animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 67701-33-1

Glycerides, C14-18 mono- and di- was tested for its skin irritation potential according to OECD Guideline 404 and in compliance with GLP (Gomond, 2000). Three New Zealand White rabbits were exposed to 0.5 g of the crunched test substance in mineral oil for 4 h under semi-occlusive conditions. The vehicle was similarly applied to the other site of the animals and served as control. Skin reactions were assessed using the Draize scheme 24, 48 and 72 h after removal of the test substance. Slight erythema was observed in 2 of 3 animals 24 and 48 h after patch removal, which was fully reversible within 48 and 72 h, respectively. In the third animal no erythema was observed. No oedema occurred in any of the tested animals and no skin reactions were observed on the control sites of the animals treated with the vehicle alone. All animals showed the expected increase in body weight and no clinical signs of toxicity were observed during the experiment. The individual mean erythema scores over the 24, 48 and 72 h reading time points were 0.3/0/0.7 and edema scores were 0 for the 3 animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

Furthermore, two studies are available investigating the skin irritation potential of Glycerides, C14-18 mono- and di- in rabbits. Both studies (the so called Burckhardt test and a patch test) did not follow a specific guideline and skin reactions were not evaluated according to the Draize scoring system (Gloxhuber, 1975a and b). As no further details were given on the test conditions, both studies could not be taken into account for hazard assessment. However, both tests revealed no visible skin reactions up to the end of a 24-h observation period.

In addition, the skin irritation potential of the test substance was investigated in two studies with hairless mice, which were also not performed according to relevant guidelines (Gloxhuber, 1975 and 1977). However, in both skin irritation tests, no skin reactions were observed after daily treatment with the test substance for 5 days or 2 weeks, respectively.

CAS No. 67784-87-6

The skin irritation potential of Glycerides, palm-oil mono- and di-, hydrogenated was investigated in 20 male and female volunteers each according to the modified Duhring-chamber test and under conditions of GCP (BASF, 1996). The test substance at 20% AS in 60% aqueous solution of cosmetic alcohol was applied to an occlusive patch and placed on the back of the volunteers for a period of 24 h. Skin reactions were scored 6, 24, 48 and 72 h after exposure to the test substance. The test substance-induced skin reactions were compared to those of negative (cosmetic alcohol) and positive reference substances (0.5% SDS, and 1.0% Texapon N28) to assess skin compatibility. In all volunteers, slight erythema was noted at 1/80 readings. Slight, moderate and strong scaling was observed at 5/80, 3/80 and 1/80 readings, respectively. No edema and no fissures occurred after exposure to the test substance. The mean scores after 6, 24, 48 and 72 h were 0.05 for erythema and 0.75 for erythema, oedema, scaling and fissure, and thus comparable to those obtained for the negative reference substance cosmetic alcohol (0.05, 0.30). The positive reference substance induced erythema and oedema as expected (1% AS Texapon N25:0.80, 2.20; 0.5% AS sodium dodecyl sulphate: 2.90, 8.10). Based on the results of this study, the test substance was considered to be non-irritating to human skin.

CAS No. 91845-19-1

A skin irritation study was conducted with Glycerides, C16-18 and C18-hydroxy mono- and di- according to EU method B.4 and in compliance with GLP (Kästner, 1985). The undiluted test substance (0.5 g) was applied for 4 h to the shaved skin of 5 New Zealand White rabbits under occlusive conditions (Sasol, 1987). The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 6 days after removal of the dressing. At the 24 and 48 h reading time points, 1/5 animals per time point showed a slight erythema, which was fully reversible within 48 and 72 h, respectively. In one animal, well-defined erythema was observed at the 24 h reading, which decreased to slight erythema at 48 h reading and was fully reversible within the 6-day observation period. No edema formation was observed in the animals at any reading time point during the study period. No signs of systemic toxicity and no effects on body weights were observed in the animals. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.4 and 0 for all 5 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 91744-13-7

The skin irritation potential of Glycerides, C14-18 and C16-22-unsatd. mono- and di- was investigated in a GLP-conform study performed according to OECD guideline 404 (Steiling, 1990). 0.5 mL of the test substance was applied for 4 h the shaved skin of 3 Kleinrussen, Chbb:HM rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48, 72 h as well as 7 days after removal of the dressing. In one animal, slight erythema persisted up to the 72 h, but was fully reversible within the 7-day observation period. In the two other animals, slight erythema was either seen at the 1 or 48 h reading, but was fully reversible 24 h or 72 h after patch removal. Slight edema was only noted in one animal at both the 48 and 72 h reading time points, but fully reversed during the 7-day observation period. No signs of systemic toxicity were seen during the study. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.3/0/1.3 and 0/0/7 for the 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 85251-77-0

The skin irritation potential of Glycerides, C16-18 mono- and di- was investigated in a GLP-conform study according to OECD guideline 404 (Ruat, 1999). Six New Zealand White rabbits were exposed for 4 h to 0.5 g of the solid test substance using liquid paraffin as vehicle to form a paste for skin exposure under semiocclusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed 24, 48 and 72 h after removal of the test substance. Slight erythema occurred in 4/6 animals 24, 48 and 72 hours after patch removal, which was fully reversible within the 7-day observation period. In the other two animals, no erythema occurred. No edema occurred in any of the tested animals at any observation time point. No signs of systemic toxicity were seen. The mean erythema and edema scores over 24, 48 and 72 h were 0.5 and 0 for all 6 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No.31566-31-1

Stearic acid, monoester with glycerol was tested for its skin irritation potential according to OECD guideline 404 (Dufour, 1993). Three New Zealand rabbits were exposed to 0.5 mL (5 g of the solid test substance was mixed with 3.2 mL vaseline to a final volume of 6.7 mL) test material (concentration of 75%) for 4 hours under semi-occlusive conditions. The rabbits were observed for 72 hours. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance using the Draize scoring system. Slight erythema was only observed in one animal 1 h after application of the test substance. No erythema and no oedema occurred in any of the tested animals at the 24, 48 and 72 h observation intervals, thus resulting in mean scores of 0 for both erythema and edema over the 24, 48 and 72 h reading time points. Based on these results, the test substance is considered to be non-irritating to the skin.

The skin irritation potential of Stearic acid, monoester with glycerol was investigated in a further study according to OECD guideline 404 (Dufour, 1992). Three New Zealand rabbits were exposed for 4 h to 0.5 g of the unchanged test substance under occlusive conditions. Skin reactions were assessed 24, 48 and 72 h after removal of the test substance. No skin reactions (erythema and edema) were observed at any time point in any animal. Furthermore, no signs of systemic toxicity were noted. The mean erythema and edema scores over 24, 48 and 72 h were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 91052-54-9

The skin irritation potential of Glycerides, C16-18 mono-, di- and tri- was investigated in a GLP-conform study according to EPA OPP 81-5 (Jones, 1998). The undiluted test substance (0.5 g) was moistened with distilled water and applied for 4 h to the shaved skin of 6 New Zealand White rabbits (4 males and 2 females) under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. No erythema or edema was noted during the study period at any reading time point. No signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0 for all 6 animals. Thus, the test substance is considered to be non-irritating to the skin.

Furthermore, a human patch test was performed in 15 male and 35 female volunteers to assess the skin irritation potential of Glycerides, C16-18 mono-, di- and tri- (Tronnier, 2003). The undiluted test substance was applied once at 2 mg test substance/cm² to healthy skin on the back area of the test subjects using a commercial test patch for 48 h. After patch removal, skin reactions were evaluated immediately (48 h post-application) and 24 h later (72 h post-application). No primary skin irritation was observed 48 or 72 h after test substance application. Furthermore, no skin reactions resulting from an existing sensitisation were induced in this test. Based on these results, the test substance was considered to be non-irritating to human skin.

CAS No. 77538-19-3

The skin irritation potential of Docosanoic acid ester with 1,2,3-propanetriol was investigated in a GLP-conform study according to EU method B.4 (Bouffechoux, 1988). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved and abraded skin of 3 male New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 4 and 7 days after removal of the dressing. At 1 h post-application, no skin reactions were noted in any treated animal. At the 24 h reading time point, slight erythema was observed in 1/3 animals, which was fully reversible after further 24 h (48 h reading). No edema formation was observed in any animal at any reading time point during the study period. No signs of systemic toxicity were seen during the study. The individual mean erythema scores over the 24, 48 and 72 h reading time points were 0/0.3/0, edema scores were 0 for the 3 animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 65381-09-1

The skin irritation potential of Decanoic acid, ester with 1,2,3-propanetriol octanoate was investigated in New Zealand albino rabbits according to OECD guideline 404 and under conditions of GLP (Jones, 1988). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 3 New Zealand White rabbits. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. At 1 h post-application, very slight erythema was observed in 1/3 animals. No skin reactions were observed in any animal at the 24, 48 and 72 h reading time points. During the study period, no signs of systemic toxicity were noted in the animals. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 73398-61-5

The skin irritation potential of Triglycerides, mixed decanoyl and octanoyl was investigated in a study according to OECD guideline 404 (Jones, 1998). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 6 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24, 48 and 72 h after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation time points. No signs of systemic toxicity were seen. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0 for all 6 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 85536-06-7

The skin irritation potential of Glycerides, C8-18 was investigated in a Draize test in rabbits (Draize, 1944). In this study, the undiluted test substance (0.5 g) was applied to the shaved or abraded dorsal skin of 3 rabbits (Kracht, 1965). The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24 and 72 h after removal of the dressing. No reactions were observed on shaved or abraded skin at any reading time point. During the study period, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over 24 and 72 h were 0 for all 3 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS No. 67701-26-2

The skin irritation potential of Glycerides, C12-18 was investigated in a GLP-conform study performed according to EPA OPP 81-5 (Jones, 1988). The test substance (0.5 mL) was applied for 4 h onto the shaved skin of 6 New Zealand White rabbits under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. Slight erythema was observed in 1/6 animals at the 1 and 24 h reading time points, respectively. At 48 h reading, slight erythema was observed in 3/6 animals. No edema was observed in the animals at any reading time point. No signs of systemic toxicity were seen during the study. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.22 and 0 for all 6 animals. Thus, the test substance is considered to be non-irritating to the skin.

A further skin irritation study was conducted with Glycerides, C12-18 according to Federal Register 1973, Vol. 38, No. 187, 1500.41 and similar to OECD guideline 404 (Driscoll, 1980). The undiluted test substance (0.5 mL) was applied for 24 h to the shaved (intact and abraded) skin of 6 New Zealand White rabbits under occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 24 and 72 h after removal of the dressing. At the 24 h reading time point, slight erythema on the intact skin was observed in 3/6 animals, which had fully reversed at the 72 h reading. Slight erythema on the abraded skin was observed in 5/6 animals, but this effect was also fully reversible at the 72 h reading. No edema was observed in any animal at any reading time point, neither on the intact nor on the abraded skin. Furthermore, no signs of systemic toxicity were observed in the animals. The mean erythema and edema scores over the 24, 48 (extrapolated from the 24 h reading time point) and 72 h reading time points were 0.33 and 0 for all 6 animals treated on the intact skin. Thus, the test substance is considered to be non-irritating to the skin.

A third study is available investigating the skin irritation potential of Glycerides, C12-18 in rabbits (Gloxhuber, 1976). The study did not follow a specific guideline and skin reactions were not evaluated according to the Draize scoring system but by the use of the Burckhardt test. In this experiment, the test substance in olive oil at a concentration of 50% in olive oil was repeatedly applied to the shaved skin of the animals for 30 min. At the end of the 24-h observation period, no visible skin reactions were observed. As the applied test does not meet important criteria of today standard methods, the results of this study were not taken into account for hazard assessment.

CAS No. 97593-30-1

The skin irritation potential of C12: Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a GLP-conform study according to OECD guideline 404 (Gmelin, 2008). The undiluted test substance (0.5 mL) was applied to the dorsal skin of 3 female Crl:KBL(NZW)BR rabbits under semiocclusive conditions. In the initial test, one female was exposed to the test substance for 3 min, 1 h and 4 h. As no corrosive effect was observed in the initial test, a confirmatory test using two additional animals was conducted. Animals were treated with the test substance for a period of 4 h. The untreated site of the animals served as control. Skin reactions were assessed 24, 48 and 72 h after removal of the test substance. In 2/3 animals, slight erythema was observed 1 h after test after exposure. In one of these animals, erythema persisted over the 24 and 48 h reading time points, but was fully reversible within the 72-h observation period. In the other animals, no erythema was seen 24, 48 and 72 h after patch removal. No edema occurred in any of the tested animals at any observation time point. No signs of systemic toxicity were seen. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.7/0/0 in one animal and 0 in the two other animals, respectively. Thus, the test substance is considered to not be irritating to the skin.

The non-irritating potential was further supported by an in vitro skin corrosion test using a human skin model test performed according to OECD guideline 431 under GLP conditions (Vohr, 2007). Within this assay, three replicates of intact reconstructed human epidermis (EST-1000) were treated with 0.05 mL (ca. 83 µL/cm²) of the undiluted test substance for 3 min and 1 h, respectively. Cells treated with 0.9% NaCl served as controls. After exposure to the test substance, cell viability was determined compared to the control. The cell viability after 3 min exposure was greater than 50% and the cell viability after 1 h exposure was greater than 15%. Under the conditions of this in vitro study, the test material was considered to be non-corrosive to reconstructed human epidermis.

CAS No. 736150-63-3

The skin irritation potential of Glycerides, castor-oil.mono, hydrogenated, acetates glycerol was investigated in a GLP-conform study according to OECD guideline 404 (Arcelin, 2003). The test substance (0.5 mL) was applied for 4 h to the shaved skin of 3 New Zealand White rabbits (1 male and 2 females) under semiocclusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48, 72 h as well as 7 days after removal of the dressing. In two animals, slight erythema persisted up to the 72 h, but was fully reversible within the 7-day observation period. In the remaining animal, slight erythema was seen at the 1, 24 and 48 h reading time points, but was fully reversible 72 h after treatment. In one male and one female, slight edema was noted at the 24 h reading time point, but was fully reversed at the 48 h reading time point. No signs of systemic toxicity were seen during the study. Over the 24, 48 and 72 h reading time points, the mean erythema scores were 1.33/1/1 and the mean edema scores were 0.33/0.33/0 for the 3 animals, respectively. Thus, the test substance is considered to be non-irritating to the skin.

Eye irritation

CAS No. 142-18-7

An eye irritation study was conducted with 2,3-dihydroxypropyl laurate according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics"(Sterner, 1997). The solid test material (0.1 g) was placed into the conjunctival sac of the left eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h as well as 4, 5, 6 and 7 days after application. At the 1, 2 and 8 h reading time points, no corneal opacity and iritis were observed. At this time points, slight to moderate conjunctival redness and moderate to strong chemosis and discharge were seen in all animals. 24 h post-application, corneal opacity was observed in 2/6 animals which was fully reversible within 72 h and 96 h, respectively. Slight to moderate conjunctival redness was observed in all animals 24 h post-application. These effects were fully reversible within 48 h (1/6 animals), 72 h (1/6 animals) or 5 days (4/6 animals). Slight to strong discharge was observed in all animals 24 h post-application. These effects were fully reversible within 72 h (5/6 animals) or 4 days (1/6 animals). Test substance application into the rabbit eye induced no iridial effects at any observation time point. No further local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0.3, 0, 1.3 and 1 for all 6 animals, respectively. Thus, the test substance was not considered as eye irritant.

CAS No. 25496-72-4

The eye irritation potential of Glycerol monooleate was investigated in 1 male and 8 female New Zealand albino rabbits according to the FDA guideline “Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics”. The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye, whereas the other eye remained untreated and served as control (Rzucidlo, 1967). In 3 of 9 animals, the test substance was rinsed 2 sec after treatment. In the other 6 animals, the test substance remained in the eye without washing. The eyes were examined and scored 1, 24, 48, 72 and 96 h as well as 7 days after instillation. Chemosis scoring was not performed. Animals exposed to a single application without washing did not show any signs of eye irritation. In contrast, 1/3 animals showed a slight conjunctival irritation (conjunctivae score 2 at reading time point 1 h after substance application) when the substance was rinsed away with water. As the effect was reversible within 24 h and the exposure to the test substance occurred for only 2 sec, the effect might be due to the washing procedure. No further local or systemic toxic effects were reported. The mean cornea, iris and conjunctivae scores after 24, 48, and 72 h were 0 for all 9 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 66085-00-5

An eye irritation study was performed with Glycerol monoisostearate according to OECD guideline 405 and under conditions of GLP (Saboureau, 1989). The undiluted test substance (0.1 mL) was instilled into one eye of 3 New Zealand White rabbits each. The other eye remained untreated and served as control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48 and 72 h after test substance instillation. Slight conjunctival enanthema, slight chemosis and profuse lacrimation were observed in all 3 animals at 1 h post-instillation. Slight enanthema was still observed in 2/3 animals at the 24 h reading time point, but was fully reversible within 48 h. Chemosis and lacrimation were no longer apparent at the 24, 48 and 72 h reading time points. No cornea or iris lesions were observed in any animal at any time point. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals. The mean score for conjunctivae over 24, 48, and 72 h was 0.22 for the all animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 620-67-7

The eye irritation potential of Propane-1,2,3-triyl trisheptanoate was investigated according to OECD guideline 405 and in compliance with GLP (Mürmann, 1993). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 male Small White Russian (Chbb:HM) rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. Within one hour, the administration of the test substance resulted in marked hyperaemia of some blood vessels in all 3 animals. After 24-72 h, no further symptoms of irritation to the eye mucosa and cornea were observed in any of the animals. Only the skin of the outer eyelids showed slight erythema after 24 h in all animals, which subsided after 48 h. Test substance instillation into the rabbit eye induced no iridial effects at any observation time point. No further local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 555-43-1

An eye irritation study was performed with Glycerol tristearate according to OECD guideline 405 and under conditions of GLP (Krueger, 1998). The solid test substance (0.1 g) was instilled into one eye of 3 male Small White Russian (Mol. Russian, Chbb:MH) rabbits each. The other eye remained untreated and served as control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48, 72 h and 6 days after test substance application. At the 1 h reading, some definitely hyperaemic (injected) blood vessels in 1/3 animals and diffuse, crimson red coloured mucous membranes (individual vessels were not easily discernible) in 2/3 animals were observed. At the same time point, swelling above normal of lids accompanied by nictating membranes and discharge in form of white mucous was noted in all 3 animals. The swelling of conjunctivae was fully reversible within 24 h. 24-72 h post-application, the conjunctivae of all 3 animals still showed some definitely hyperaemic blood vessels, which were fully reversible within the 6-day observation period. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively. The mean scores for conjunctivae after 24, 48, and 72 h were 1/1/1 for the 3 individual animals.Thus, the test substance was not considered as eye irritant.

CAS No. 26942-95-0

An eye irritation study was performed with 1,2,3-propanetriyl triisooctadecanoate according to OECD guideline 405 and under conditions of GLP (Saboureau, 1989). The undiluted test substance (0.1 mL) was instilled into one eye of 3 New Zealand White rabbits each. The other eye remained untreated and served as control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48 and 72 h after test substance application. Slight enanthema together with lacrimation was observed in all animals at 1 h post-instillation. The enanthema persisted in all animals at the 24 h reading time point, but was fully reversible within 48 h. Only one animal showed slight chemosis at the 1 h reading time point. No cornea or iris lesions were observed in any animal at any time point. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals, respectively. The mean score for conjunctivae over 24, 48, and 72 h was 0.3 for each individual animal.Thus, the test substance was not considered as eye irritant.

CAS No. 67701-33-1

Glycerides, C14-18 mono- and di- was tested for its eye irritation potential according to OECD guideline 405 and in compliance with GLP (Gomond, 2000). The solid test material (0.1 g) was ground to a fine dust and instilled into the conjunctival sac of one eye of three New Zealand White rabbits each. Examination of the effects on the eyes was scored 1, 24, 48 and 72 h after test substance instillation according to the method of Draize. Slight to moderate redness of conjunctivae occurred in all three tested animals, which was fully reversible within 72 h. At the 1 h reading time point, slight chemosis was observed in all animals, and persisted in 2 of 3 tested animals up to 24 h after test substance instillation. However, chemosis was fully reversible within 48 h in all animals.During the 72-h observation period, no clinical signs of toxicity were noted. The mean cornea and iris scores after 24, 48, and 72 h were 0 for all 3 animals. The mean scores for conjunctivae and chemosis over 24, 48, and 72 h were 1/1/0.7 and 0/0.3/0.3 for the 3 individual animals, respectively. Thus, the test substance was not considered as eye irritant.

Two further studies performed according to the Draize method are available investigating the eye irritation potential of Glycerides, C14-18 mono- and di- in New Zealand White rabbits (Gloxhuber, 1975 and 1977). In both studies, conjunctival reactions were observed which were fully reversible within 24 or 48 h, respectively. However, individual eye irritation scores were not reported. Based on the lack of information, none of these results were considered conclusive and therefore not taken into consideration for hazard assessment.

CAS No. 91845-19-1

An eye irritation study was conducted with Glycerides, C16-18 and C18-hydroxy mono- and di- according to EU method B.5 and in compliance with GLP (Kästner, 1985). The solid test material (0.1 g) was placed into the conjunctival sac of one eye of 5 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 6, 24, 48 and 72 h after application. At the 1 h reading time point, all animals showed diffuse crimson redness to diffuse beefy redness of the conjunctivae, which decreased in all animals and was fully reversible within 24 h in 4/5 animals and within 48 h in 1/5 animals, respectively. Slight chemosis was observed in 1/6 animals and 3/5 animals showed slight exudation 6 h after application. Both effects were fully reversible within 24 h. No effects on iris or cornea were observed in any animal during the study period. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores over 24, 48, and 72 h were 0 for all 5 animals, respectively. The mean score for conjunctivae over 24, 48, and 72 h was 0.07 for all 5 animals.Thus, the test substance was not considered as eye irritant.

CAS No. 91744-13-7

The eye irritation potential of Glycerides, C14-18 and C16-22-unsatd. mono- and di- was investigated according to OECD guideline 405 and in compliance with GLP (Steiling, 1990). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 male Kleinrussen (Chbb:HM) rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. No corneal opacity, iritis, conjunctivae or chemosis were observed in any animal at any reading time point. All animals showed slight to moderate exudation exclusively at the 1 h reading time point. No further local or systemic toxic effects were reported. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 85251-77-0

The eye irritation potential of Mono and diglycerides of fatty acids (Glycerides, C16-18 mono- and di-) was investigated according to OECD guideline 405 and in compliance with GLP (Ruat, 1999). The solid test material (54 mg) was placed into the conjunctival sac of one eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. Slight to moderate effects on the conjunctivae (redness and chemosis) and slight effects on the iris (congestion) were observed in all animals 1 h after test substance application. In one animal, effects on the iris persisted up to 48 h and reversed thereafter. No effects on cornea were observed in any animal tested. No further local or systemic toxic effects were observed. The mean cornea, conjunctivae and chemosis scores over 24, 48, and 72 h were 0 for all 6 animals, respectively. The effects on iris over 24, 48, and 72 h were scored 0.11 for all 6 animals.Thus, the test substance was not considered as eye irritant.

CAS No. 91052-54-9

An eye irritation study was conducted with Glycerides, C16-18 mono-, di- and tri- according to EPA OPP guideline 81-4 and in compliance with GLP (Jones, 1988). The solid test material (72 mg) was placed into the conjunctival sac of the left eye of 6 New Zealand White rabbits each (1 male and 5 females). The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At 1 h post-application, slight iritis was observed in 2/6 animals, being fully reversible until the 24 h reading time point. Slight and moderate conjunctival redness was observed in 1/6 and 5/6 animals, respectively. These effects fully reversed 24 h post-application in 4/6 animals and in 2/6 animals 48 post-application Very slight and slight swelling was observed in 3/6 rabbits 1 h post-application, respectively. The effects fully reversed 24 h post-application. At the 1 h reading time point, all animals showed slight discharge, but this effect was not observed at the following reading time points.. No effects on the eyes were noted in any animal at the 48 and 72 h reading time points. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores over 24, 48, and 72 h were 0 for all 6 animals, respectively. The mean score for conjunctivae over 24, 48, and 72 h was 0.1 for all 6 animals.Thus, the test substance was not considered as eye irritant.

CAS No. 77538-19-3

The eye irritation potential of Docosanoic acid ester with 1,2,3-propanetriol was investigated according to OECD guideline 405 and in compliance with GLP (Bouffechoux, 1998). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 male New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48, 72 h and 7 days after application. At the 1 h reading time point, slight lacrimation was observed in all 3 animals and persisted up to the 24 h reading time point in 1/3 animals. No further local or systemic effects were observed in any animal at any reading time point.. The mean cornea, iris, conjunctivae and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 65381-09-1

An eye irritation study was conducted with Decanoic acid, ester with 1,2,3-propanetriol octanoate according to OECD guideline 405 and in compliance with GLP (Jones, 1988). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. Conjunctival redness (score 1) was observed in all 3 animals at 1 h post-instillation. At the same time point, swelling above normal (chemosis score 1) was observed in 1/3 animals. No effects were observed in any animal at the 24, 48 and 72 h readings. No further local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 73398-61-5

An eye irritation study was performed with Triglycerides, mixed decanoyl and octanoyl according to EPA OPP guideline 81-4 and in compliance with GLP (Jones, 1988). The undiluted test substance (0.1 mL) was instilled into the conjunctival sac of one eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1 h reading, iridial inflammation was observed in 1/6 animals, which was fully reversible within 24 h. At the same time point, mild to moderate conjunctivae effects were apparent in all animals. In 1/6 animals, mild conjunctivae redness and chemosis was still apparent after 24 h, but was fully reversible at the 48 h reading. In the remaining 5/6 animals, conjunctivae irritation was fully reversible within 24 h. No adverse corneal effects were noted in any animal at any observation time point. No further local or systemic toxic effects were observed. The mean scores for conjunctivae and chemosis after 24, 48, and 72 h were 0.06 for all 6 animals, respectively. The mean scores for cornea and iris over 24, 48, and 72 h were 0 for all 6 animals.Thus, the test substance was not considered as eye irritant.

CAS No. 85536-06-7

An eye irritation study was conducted with Glycerides, C8-18 according to the Draize test in rabbits (Draize, 1944). In this study, the undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 4 rabbits each (Kracht, 1965). The other eye remained untreated and served as control. The eyes were examined and scored 1, 3, 5, 24, 48 and 72 h after application. No iris scoring was performed. At 1 h post-instillation, slight conjunctival redness was observed in all 4 animals, which was fully reversible within 24 h. No effects on cornea and no chemosis were noted in any treated animal. No further local or systemic toxic effects were observed. The mean cornea, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 67701-26-2

The eye irritation potential of Glycerides, C12-18 was investigated according to EPA OPP guideline 81-4 and in compliance with GLP (Jones, 1988). The undiluted test material (0.1 mL) was applied into the conjunctival sac of one eye of 6 New Zealand White rabbits each (5 males and 1 female). The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1 h reading, slight or moderate conjunctival redness was observed in 2/6 and 4/6 animals, respectively. At the same time point, slight or moderate chemosis was observed in 4/6 and 1/6 animals, respectively. A slight discharge was observed in 4/6 animals. At the 24 h reading time point, slight conjunctival redness was observed in 2/6 animals, which was fully reversible within the following 24 h. No conjunctival redness was observed in any animal 48-72 h after test substance instillation. No corneal opacity, iritis or chemosis were observed in any animal at any reading time point. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores after 24, 48, and 72 h were 0 for all 6 animals, respectively. The mean score for conjunctivae after 24, 48, and 72 h was 0.1 for all 6 animals.Thus, the test substance was not considered as eye irritant.

Furthermore,an eye irritation study was conducted with Glycerides, C12-18 according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics, 1959"(Cremer Oleo GmbH & Co. KG, 1972). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of nine New Zealand White rabbits each. The other eye remained untreated and served as control. In the first 3 rabbits, the treated eyes remained unwashed. The treated eyes of the remaining animals were washed with 20 mL lukewarm water after 2 and 4 s, respectively. The eyes were examined and scored 24, 48 and 72 h as well as 4 and 7 days after application. No corneal opacity and no iritis were observed in any animal at any reading time point. At the 24 and 48 h reading time point, conjunctival irritation was very slight, being only marginally worse in the unwashed eyes, but fully reversible within 3 days after test substance instillation. The mean cornea, iris and chemosis scores after 24, 48, and 72 h were 0 for the unwashed eyes of all 3 animals. The mean scores for conjunctivae over 24, 48, and 72 h were 1/1.3/1 for the unwashed eyes of the 3 individual animals. Thus, the test substance was not considered as eye irritant.

One further study performed according to the Draize method is available investigating the eye irritation potential of Glycerides, C12-18 in New Zealand White rabbits (Gloxhuber, 1976). In this study, 0.05 mL of the diluted test substance (50% in olive oil) caused slight reactions (not further specified) which had completely cleared up after 24 h. It was stated that these findings were probably caused by foreign body reactions, as the test item had to be warmed before being administered. However, individual eye irritation scores were not reported. Based on the lack of information, these results were not considered conclusive and therefore not taken into consideration for hazard assessment.

CAS No.8001-78-3

Castor oil, hydrogenated was tested for its eye irritation potential similar to OECD Guideline 405 (Kästner, 1981). The test material (0.1 mL) was instilled into the conjunctival sac of one eye of four New Zealand White rabbits each. The animals were observed for 72 hours. Irritation was scored 24, 48 and 72 hours after instillation according to the method of Draize. Conjunctiva and chemosis scores were not given as individual data. However, only slight changes were reported for conjunctivae and chemosis, which were described to be fully reversible within 48 hours. The mean cornea and iris scores after 24, 48, and 72 h were 0 for all 4 animals. Thus, the test substance was not considered as eye irritant.

CAS No. 97593-30-1

An eye irritation study was performed with C12: Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates according to OECD guideline 405 and under conditions of GLP (Gmelin, 2008). The undiluted test substance (0.1 mL) was installed into one eye of 3 female Crl:KBL(NZW)BR rabbits each. The other eye remained untreated and served as control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48 and 72 h after test substance application. 1 h post-instillation, moderate conjunctival redness and very slight chemosis were observed in all 3 animals. Slight conjunctival redness and very slight chemosis were observed at the 24 h reading time point in 3/3 and 2/3 animals, respectively. Both effects were fully reversible after further 24 h (48 h reading time point). No corneal opacity or iritis was noted in any animal at any reading time point. No further local or systemic toxic effects were observed. The mean cornea and iris scores after 24, 48, and 72 h were 0 for all 3 animals. The mean scores for conjunctivae and chemosis over 24, 48, and 72 h were 0.3 and 0/0.3/0.3 for the 3 individual animals, respectively.Thus, the test substance was not considered as eye irritant.

CAS No. 736150-63-3

An eye irritation study was performed with Glycerides, castor-oil.mono, hydrogenated, acetates according to OECD guideline 405 and under conditions of GLP (Arcelin, 2003). The undiluted test substance (0.1 mL) was instilled into one eye of 1 male and 2 female New Zealand White rabbits each. The other eye remained untreated and served as control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48 and 72 h after test substance application. Slight conjunctival redness was observed in all animals at the 1 h reading time point and persisted in 2/3 animals up to 24 h after treatment. At the following readings, no effects on conjunctival redness were observed in any animal. Slight swelling of the conjunctivae was noted in one animal at the 1 h examination, but was fully reversible within 24 h. At the same time point, slight ocular discharge was present in all animals, but was fully reversible at the 24 h reading time point. No effects on cornea and iris were observed during the study period in any animal. No further local or systemic toxic effects were observed. The mean cornea, iris and chemosis scores over 24, 48, and 72 h were 0 for all 3 animals, respectively. The mean scores for conjunctivae over 24, 48, and 72 h were 0.33/0.33/0 for the 3 individual animals.Thus, the test substance was not considered as eye irritant.

Overall conclusion for skin and eye irritation

The skin and eye irritation potential of Glycerides has been investigated in numerous studies, including studies with human volunteers.

All available dermal studies indicate that the substances tested are not irritating to the skin. Only in one animal study, the substance Propane-1,2,3-triyl trisheptanoate (CAS No. 620-67-7) showed irritating potential. However, in a second independent animal study and in a study with human volunteers the substance was not skin irritating. Thus, based on the weight of evidence from the available animal and human data, Propane-1,2,3-triyl trisheptanoate is considered to be not skin irritating.

No eye irritating properties were reported in any of the available studies on Glycerides.

Based on the available data and following the category approach, all members of the Glycerides category are considered to be not irritating to the skin and eyes.

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 Glycerides category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled 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.