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 polyol esters category comprises of 51 aliphatic esters of polyfunctional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The category contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C28, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9,branched C14 – C22 building mono-, di-, tri-, and tetra esters with an alcohol (i.e.polyol).

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 and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 7.1 and 13) and within Section 5.1 of the CSR.

 

Data matrix for skin/eye irritation

CAS

Skin Irritation/Corrosion

Eye Irritation/Corrosion

NPG esters

68855-18-5 (a)

Not irritating

Not irritating

31335-74-7

RA: CAS 68855-18-5

RA: CAS 97281-24-8

RA: CAS 68855-18-5

RA: CAS 97281-24-8

70693-32-2

RA: CAS 97281-24-8

RA: CAS 97281-24-8

former CAS 85186-86-3

RA: CAS 85186-86-3

RA: CAS 85186-86-3

85186-86-3

Not irritating

Not irritating

85186-95-4

RA: CAS 85186-86-3

 

RA: CAS 85186-86-3

 

85116-81-0

RA: CAS 85186-86-3

RA: CAS 85186-86-3

91031-27-5

RA: CAS 85186-86-3

RA: CAS 85186-86-3

 

42222-50-4

Not irritating

Not irritating

85005-25-0

RA: CAS 403507-18-6

RA: CAS 85186-86-3

RA: CAS 403507-18-6

RA: CAS 85186-86-3

TMP esters

78-16-0 (a)

Not irritating

Not irritating

91050-88-3 (b)

RA: CAS 91050-90-7

RA: CAS 11138-60-6

RA: CAS 91050-90-7

RA: CAS 11138-60-6

97281-24-8

Not irritating

Not irritating

11138-60-6

Not irritating

Not irritating

91050-89-4

Not irritating

Not irritating

85566-29-6

RA: CAS 91050-90-7

RA: CAS 11138-60-6

RA: CAS 403507-18-6

RA: CAS 11138-60-6

(Formerly 85186-89-6)

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

403507-18-6

Not irritating

Not irritating

68002-79-9

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

(Formerly 85005-23-8)

EC 931-531-4

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

91050-90-7

Not irritating

Not irritating

68002-78-8

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

(Formerly 57675-44-2)

EC 931-461-4

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

85186-92-1

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

68541-50-4

RA: CAS 91050-90-7

RA: CAS 403507-18-6

RA: CAS 91050-90-7

RA: CAS 403507-18-6

PE esters

15834-04-5 (b)

RA: CAS 68424-31-7

RA: CAS 67762-53-2

RA: CAS 68424-31-7

RA: CAS 67762-53-2

85116-93-4

Not irritating

Not irritating

85711-45-1 (a)

RA: CAS 85116-93-4

RA: CAS 85116-93-4

25151-96-6

RA: CAS 85116-93-4

RA: CAS 68424-31-7

67762-53-2

Not irritating

Not irritating

(Formerly 68441-94-1)

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

(Formerly 68424-30-6)

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

68424-31-7 (c)

RA: CAS 68424-31-7

RA: CAS 68424-31-7

68424-31-7 (d)

RA: CAS 68424-31-7

 

RA: CAS 68424-31-7

 

68424-31-7 (e)

RA: CAS 68424-31-7

 

RA: CAS 68424-31-7

 

71010-76-9

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

RA: CAS 189200-42-8
RA: CAS 68424-31-7
RA: CAS 67762-53-2

68441-68-9

Not irritating

RA: CAS 68424-31-7
RA: CAS 189200-42-8

85586-24-9

RA: CAS 189200-42-8
RA: CAS 68424-31-7

RA: CAS 189200-42-8
RA: CAS 68424-31-7

85049-33-8

RA: CAS 85116-93-4

RA: CAS 68424-31-7

RA: CAS 85116-93-4

RA: CAS 68424-31-7

91050-82-7

RA: CAS 85116-93-4

RA: CAS 85116-93-4

19321-40-5

RA: CAS 85116-93-4

RA: CAS 85116-93-4

68604-44-4

RA: CAS 85116-93-4

RA: CAS 85116-93-4

62125-22-8

Not irritating

Not irritating

68440-09-5

RA: CAS 85116-9-4

RA: CAS 85116-9-4
RA: CAS 68424-31-7

189200-42-8

Not irritating

Not irritating

 

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

 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.

CAS 68434-31-7 – Lead registrant

Separate registration of CAS 68434-31-7

Separate registration of CAS 68434-31-7 (2-ethylhexanoic acid)

 

Discussion

Skin Irritation

Several studies assessing skin irritation potential of substances within the polyol esters category are available.

CAS 68855-18-5

A primary dermal irritation study was performed with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECD Guideline 404 and GLP (Doyle, 1996). The shaved left flanks of three female New Zealand White rabbits were exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed according to the Draize scoring system 1, 24, 48 and 72 hours after removal of the test substance. No signs of skin erythema or oedema were observed in any of the tested animals at any reading time point. Both mean erythema and oedema scores were zero after 24, 48, and 72 h. Thus, the test material is not considered irritating to the skin in this study.

CAS 31335-74-7

A short summary with limited reporting is available with regard to skin irritation after dermal application of 2,2-dimethyl-1,3-propanediyl dioctanoate (CAS 31335-74-7) to the skin of three female rabbits (Robinson, 1993). The animals were observed for 4 days following exposure. Skin reactions were assessed according to the Draize scoring system 0.5-1, 24, 48, 72, and 96 hours after exposure. Well defined erythema (grade 2) was observed in one animal at 24 hour reading point and persisted until the end of the observation period (Day 4). Very slight erythema (grade 1) was observed in two other animals at the 24 hour reading point. This skin effect was not reversible within 4 days.

Very slight oedema was observed in one animal at the 24 hour time point and persisted until the end of the observation period. Another animal showed a very slight oedema, which was completely reversible within 3 days. Based on this data, the erythema scores over 24, 48, and 72 h were 2, 1, and 1, respectively, for the three animals. The respective oedema scores reported were 1, 0, and 0.67 Thus, the test material is not considered irritating to the skin in this study.

CAS 85186-86-3

A primary dermal irritation study was performed with Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS 85186-86-3) according to OECD Guideline 404 and GLP (Pooles, 2012). The shaved backs of three New Zealand White rabbits were exposed to 0.5 mL unchanged test material for 3 minutes, 1 hour and 4 hours (initial test with one animal) and 4 hours (confirmatory test with two animals) under semiocclusive conditions. The rabbits were observed for 7 days following exposure. Skin reactions were assessed according to the Draize scoring system 1, 24, 48 and 72 hours and 7 days after removal of the test substance. Very slight erythema was noted at one treated skin site at the 24 h observation with well-defined erythema and very slight oedema noted at the 48 and 72 h observations. No evidence of skin irritation was noted at two treated skin sites during the study. The mean erythema score for animals #1 and #2 at the 24, 48, and 72 hour reading time points was zero, whereas the respective mean score for animals #3 was 1.7. Similarly, the mean oedema score for animals #1 and #2 at the 24, 48, and 72 hour reading time points was zero, whereas the respective mean score for animals #3 was 0.7. The skin irritation observed in animal #3 was fully reversible within 7 days. Thus, the test material is not considered irritating to the skin in this study.

CAS 42222-50-4

The skin irritation potential of 2,2-dimethyl-1,4-propanediyl dioleate (CAS 42222-50-4) was determined in the Human Skin Model Test following EU-Method B.46 and OECD 439, respectively, under GLP conditions (Andres, 2012).

Three tissues of the human skin model EpiDerm TM were treated with the test item for 1 h. 30 µL of the liquid test item were applied to each tissue.

DPBS-Buffer and 5% SDS-solution were used as negative and positive controls, respectively.

At the end of the treatment, no irritation potential of the test substance was observed, since the mean relative cell viability of tissue after 1 h treatment followed by a 42-h post-treatment incubation period was 100.3. This value is well above the threshold for irritation potential (50%) compared to the negative control. The positive and negative controls showed the expected results: the mean values of relative cell viability of positive and negative control are 7.8 and 100 respectively.

On the basis of these findings it can be concluded that 2,2,-dimethyl-1,4-propanediyl dioleate is considered to be not irritant in the Human Skin Model Test.

CAS 78-16-0

There are 6 skin irritation studies available for 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (CAS 78-16-0).

A primary dermal irritation study was performed according to EU Method B.4 and GLP (Weterings, 1987). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed approx. 1, 24, 48 and 72 hours after removal of the test substance. Very slight erythema and very slight edema were observed in all animals 24 h after treatment. The mean erythema score over 24, 48 and 72 hours were 0.66 for the animal# 1 and 0.33 for animal #2 and #3. The mean edema score were 0.33 for all three animals. All effects were fully reversible within 72 h (erythema, animal #1) or 48 h (all other effects and animals), respectively.

In a second primary dermal irritation study performed according to OECD Guideline 404 (Robinson, 1991) the skins of three male New Zealand white rabbits were exposed to test material for 4 hours. Skin reactions were assessed 1, 24, 48 and 72 hours and up to 19 days after removal of the test substance. Well defined to moderate or severe erythema was observed for two or three days after application. This reversed and no signs of erythema were observed 6 or 19 days after application. Very slight to severe edema was observed for the first 3 days. No edema was seen after this time. Additional signs of irritation included slight desquamation and slight to moderate thickening of the application site seen in two animals. All treated skin sites appeared normal at the 19 day observation. Mean erythema scores over 24, 48 and 72 hours were 3, 2.3, and 2 in animal #1, #2, and #3 respectively.

Mean edema score over 24, 48 and 72 hours were 3.3, 3, and 2.7 in animal #1, #2, and #3 respectively. On the basis of the test findings the test substance was found to be a category 2 irritant.

Two further studies with insufficient documentation are available with limited information on guideline and study design. In the first study, weak skin reactions were observed in test animals after substance application: in 2/3 animals, erythema with a mean overall score of 0.3 - 0.7 have been observed. In contrast, only 1 animal revealed slight edema (mean overall score 0.3) after substance application (Bugg 1993). The second study was conducted according to “16 CFR 1500.41” guideline (Anonymous, 1978). 3 male and female rabbits were exposed under occlusive conditions to the test substance. Observation was done for 72 h, however, readings were conducted only at 24 and 72 hours. After 24 h, slight erythema formation was observed in 4/6 animals. Two animals showed no effects on erythema formation. In all animals, the erythema formation was reversible within 72 h. No effects on edema formation were observed in any animal after 24 and 72 h. Mean erythema sand edema scores out of all 6 animals over reading time points were 0.4 and 0 respectively.

Two additional studies with insufficient documentation are available. Both studies were conducted up to 72 hours, without reading at 48 hours however not all effects were reversible at 72 hours. The study performed by Morgareidge (1974) followed guideline “16 CFR 1500.41” using 6 white albino rabbits. After 24 h exposure slight erythema and eschar formation was observed in 5/6 animals. One animal showed no effects. After 72 h slight erythema and eschar formation was detected in 3/6 animals and moderate erythema and eschar formation in 1/6 animals. Two animals showed no effects. Thus, the mean erythema score out of all six animals over the reading time points was 0.83. No edema was observed at any of the reading time points. The second study by Moreno (1977) equally followed guideline “16 CFR 1500.41” using 6 New Zealand White rabbits. After 24 h, slight or moderate erythema and eschar formation was observed in 1/6 and 5/6 animals, respectively. After 72 h slight erythema and eschar formation was detected in 3/6 animals and moderate erythema and eschar formation in 2/6 animals. One animal was free of any symptom. After 24 h, 3/6 animals showed slight and 3/6 showed moderate edema formation. After 72 h moderate edema formation was observed in one animal and slight edema formation in 2/6 animals. 3/6 animals showed no effects. The mean erythema score out of all 6 animals and over 24, 48 and 72 hours was 1.6, while the mean edema score out of all six animals over 24, 48 and 72 hours was 1.2 On the basis of these findings the test substance is considered to be as non irritating to skin. In summary, 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate is considered not to be skin irritating in regard to all studies available.

CAS 97281-24-8

A primary dermal irritation study was performed with Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane (CAS 97281-24-8) according to OECD Guideline 404 and GLP (Kästner, 1988). The shaved backs of four male Chbb:HM rabbits were exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed according to the Draize scoring system 1, 24, 48 and 72 hours after the exposure period. No signs of irritation were observed in any of the tested animals at any reading time point. Both mean erythema and oedema scores were zero after 24, 48, and 72 h. Thus, the test material is not considered irritating to the skin in this study.

CAS 11138-60-6

A primary dermal irritation study was conducted analogously with Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS #11138-60-6) (Oleon, 1990, rabbit, RL2). The back of three New Zealand White rabbits was exposed to 0.5 mL test material for 4 hours under semi-occlusive conditions. The rabbits were observed for 72 h after exposure and skin reactions were assessed using the Draize scheme periodically (24, 48 and 72 hours) after removal of the test substance. No cutaneous reactions were observed in any of the tested animals at any observation interval.

CAS 91050-89-4

A primary dermal irritation study was performed with Fatty acids, C8-10, triesters with trimethylolpropane (CAS 91050-89-4) comparable to OECD Guideline 404 (Kästner, 1983). The clipped skin of five male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under occlusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. At tape removal and after 1 h, no effects on the skin were observed. After 24 h, 3 animals showed grade 1 erythema, which persisted in 1 animal for 48 h. 72 h after exposure, all animals were free of erythema. The mean erythema score out of five animals was 0.24. No edema could be observed for the tested animals at any reading time point. Thus, the test material is not considered irritating to the skin in this study.

CAS 403507-18-6

A primary dermal irritation study was performed with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) comparable to OECD Guideline 404 and GLP (Sanders, 2002). The clipped skin of three male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. Very slight to well-defined erythema was noted in all animals one hour after patch removal and at the 24 h observation time point. Very slight erythema was seen for 2/3 animals at the 48 and 72 h observations. The mean erythema score over 24, 48 and 72 hours were 1.33 for animal #1 and #3 and 0.33 for animal #2. The mean edema scores were 0.33, 0, and 1.33 for animals#1, #2 and #3 respectively. All effects were at the latest reversible within 7 days. Thus, the test material is not considered irritating to the skin in this study.

CAS 91050-90-7

A primary dermal irritation study performed with Fatty acids, C16-18, triesters with trimethylolpropane (CAS 91050-90-7) comparable to OECD Guideline 404 and GLP (Steiling, 1989). The clipped skin of three male Kleinrussen Chbb:HM rabbits was exposed to 0.5 g unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. All 3 animals displayed very slight erythema at the 24 h reading time point. In one animal, erythema remained up to 48 h. The finding was fully reversible for all 3 animals within 48 to 72 h. No edema was observed in any animal. The mean erythema scores over 24, 48 and 72 hours were 0.7 for animal #1 and 0.3 for animals #2 and #3. Thus, the test material is not considered irritating to the skin in this study.

CAS 85116-93-4

A primary dermal irritation study was performed with Fatty acids, C16-18, esters with pentaerythritol (CAS 85116-93-4) according to OECD Guideline 404 and GLP (Steiling, 1991). The shaved backs of three male Kleinrussen Chbb:HM rabbits were exposed to 0.5 g unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for 3 days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. No erythema and no oedema occurred in any of the tested animals at any reading time point. Thus, the test material is not considered irritating to the skin in this study.

CAS 67762-53-2

A primary dermal irritation study was performed comparable to OECD Guideline 404 with fatty acids, Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) (Zolyniene, 1999). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 hours after removal of the patches the dermal effect was completely reversible. All treated skin sites appeared normal at the 72 hour observation. The mean erythema scores over 24, 48 and 72 hours were 0 for animal #1 and #2 and 0.33 for animal #3. No edema occurred in any of the tested animals at any reading time point. The test material is not considered irritating to the skin in this study.

CAS 68424-31-7

Three primary skin irritation studies were conducted to assess the skin irritation potential of Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7).

In the first primary skin irritation study, which was performed according to OECD Guideline 404 (Robinson, 1991a), the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48, 72 and 96 hours after removal of the test substance. The exposure period of 4 hours caused slight edema (grade = 1) in all animals 24 hours after removal of the test substance. The effect fully reversed within 48 hours. Erythema was seen at the test site of one animal (grade 2) and slightly at the test site of the other two animals (grade =1). Erythema reactions were completely reversed within 96 hours after removal of the test substance in all three animals. The mean erythema score over 24, 48 and 72 hours was 1.3 for animal #1 and #3 and 1.7 for animal #2. The mean edema score over 24, 48 and 72 hours was 0.3 for all three animals. All treated skin sites appeared normal at the 96 hour observation.

Two further studies, which were performed comparable to OECD Guideline 404, investigated primary dermal irritation of 0.5 mL test substance on the shaved skin of three male New Zealand White rabbits each for a single 4-hour application period (Robinson, 1991b + c). Skin reactions were assessed 1, 24, 48, 72, 96 hours and 7, 8 and 12 days after removal of the test substance. In the first study, moderate to severe erythema (maximum score = 4) and moderate to severe edema (maximum score = 4) were observed for 2 or 3 days after application in all animals. This regressed and no signs of erythema or edema were evident 4 to 12 days after application. Thickening of the skin at the application site was seen on one animal between 4 and 7 days after application. No other signs of irritations were observed. In the second study, very slight to well-defined erythema and very slight to slight oedema were observed in all animals The mean erythema score over 24, 48 and 72 hours was 1 for the first animal and 1.3 for the remaining two animals. The edema score over 24, 48 and 72 hours was 1 for the first animal and 1.7 for the remaining two animals. These reversed and no signs of erythema or oedema were evident 11 or 12 days after application. Slight desquamation at the application site of one animal was observed 7 days after application.

The test material is not considered irritating to the skin in with regard to the studies performed with Tetra-esterification products of C5, C7, C8, C10 fatty acids with pentraerythritol.

CAS 68441-68-9

A human patch test was conducted to assess the irritation potential of Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CASCAS 68441-68-9) to the skin of 11 human volunteers from the general population (Boue-Grabot, 2004). Only limited details are reported. The test substance was applied occlusive to the upper back of human volunteers and the skin reactions were recorded. None of the human volunteers showed any skin reaction at the end of the study period and the primary skin irritation index of 0 was obtained on the basis of the finding. Thus, the test material is not considered to be irritating to human skin.

Additionally, a primary dermal irritation study was performed according to OECD Guideline 404 and GLP (Steiling, 1991). The shaved skin of three male Kleinrussen, Chbb:HM rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. At the 24 h reading, very slight erythema was observed in all 3 animals (score = 1), which was fully reversed 48 h after test substance removal. All treated skin sites appeared normal at the 72 hour observation. The mean erythema score was 1 for all animals, while edema score was zero in all animals after 24, 48 and 72 h treatment. The test material is not considered irritating to the skin in this study.

CAS 62125-22-8

Three primary skin irritation studies were conducted to assess the skin irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8).

A primary dermal irritation study was performed with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) according to OECD Guideline 404 and GLP (Weterings, 1984). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. The rabbits were observed for three days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. Very slight erythema and very slight edema was observed 1 h after treatment, each in one animal. Effects were fully reversed within 24 h after treatment. The third animal was free of any skin irritation effect.

In a second primary dermal irritation study performed according to OECD Guideline 404 (Bouffechoux, 1997) the skin of three male New Zealand rabbits was exposed to the test material for 4 hours. Skin reactions were assessed 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 erythema (score = 1) in two animals which was completely reversed within 48 and 72 hours, respectively. The mean score erythema score over 24, 48 and 72 h were 1.3, 0, and 0.3 for animal #1, #2, and #3 respectively. The third animal was free of any skin irritation. All treated skin sites appeared normal at the 72 hour observation.

A third primary dermal irritation study was conducted by exposing the clipped intact and abraded flanks of 6 female New Zealand White rabbits with the test substance for 24 hours under occlusive conditions (Sugar, 1981). Skin reactions were assessed 1 and 48 hours after removal of the test substance. On the intact skin, very slight erythema was observed in 4 animals 1 hour after patch removal, which persisted for 48 hours in three animals. 1 animal showed very slight erythema from 48 hours onwards, while no edema was observed in any of the 6 animals at 48 hour reading time. Edema on the abraded skin was seen in 1 animal 1 hour after patch removal, which was not present at the 48 hour reading time point. Reversibility of erythema and edema cannot be stated due to limited observation time.

The test material is not considered irritating to the skin in these studies.

CAS 189200-42-8

A primary dermal irritation study was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8) comparable to OECD Guideline 404 and GLP (Frank, 1995). The shaved skin of six male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. No erythema and no edema occurred in any of the tested animals at any reading time point. At the 72 hour time point two animals showed desquamation. The test material is not considered irritating to the skin in this study.

Eye Irritation

Several studies assessing eye irritation potential of substances within the polyol esters category are available.

CAS 68855-18-5

Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 and in compliance with GLP (Bradshaw, 2012). 0.1 mL of the neat test material was applied as a single treatment without subsequent washing to two New Zealand white (Hsdlf:NZW) 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. No corneal or iridial effects were noted during the study. Moderate (grade 2) conjunctival irritation was noted in both animals 1 h after treatment. At the 24 h reading time point, only minimal conjunctival irritation (grade 1) was present in the animals, which was fully reversible 48 h after test substance application. Based on these findings, the cornea and iris scores of both animals over 24, 48, and 72 h were zero. The conjunctivae and chemosis scores over 24, 48, and 72 h for both animals were 1. Based on this data, the test material is not considered irritating to the eyes under the conditions of this study.

CAS 31335-74-7

A short summary is available reporting eye irritation after application of 0.1 mL neat 2,2-dimethyl-1,3-propanediyl dioctanoate (CAS 31335-74-7) to one eye each of three male rabbits (Robinson, 1993). Reporting of test conditions and results was limited. The instillation was conducted as single application without washing. The animals were observed for 3 days and reactions were assessed 1.6 - 1.7, 24, 48, and 72 hours after instillation according to the Draize scoring system. Transient conjuctival redness was observed in 2/3 animals approximately 1-2 hours after dosing. Based on this finding the mean cornea, iris, conjunctivae, and chemosis scores for all three animals over 24, 48, and 72 h were zero and thus, the test material was considered to be not irritating to the eyes under the conditions of this study.

CAS 85186-86-3

Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS 85186-86-3) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 and in compliance with GLP (Pooles, 2012). 0.1 mL of the neat test material was applied as a single treatment without subsequent washing to three New Zealand white (Hsdlf:NZW) 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. No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in two treated eyes 1 hour after treatment. Minimal conjunctival irritation was noted in two eyes at the 24 h observation and persisted in one treated eye at the 48 h observation. With regard to conjuctival irritation one treated eye appeared normal at the 24 h observation, another treated eye appeared normal at the 48 h observation, and the remaining treated eye appeared normal at the 72 h observation. Based on these findings, the mean cornea and iris scores of all three animals over 24, 48, and 72 h were zero. The conjunctivae scores over 24, 48, and 72 h were 0, 0.7, and 0.3, respectively, for the three animals. The chemosis scores over 24, 48, and 72 h were 0 for animals # 1 and #3 and 0.3 for animal #2, respectively. Based on this data, the test material is not considered irritating to the eyes under the conditions of this study.

CAS 42222-50-4

The potential of the test substance 2,2-dimethyl-1,3-propanediyl dioleate (CAS 42222-50-4) to cause ocular corrosivity or severe irritancy was assessed by conducting a by bovine corneal opacity and permeability test (BCOP) according to OECD Guideline 437 and GLP (Andres, 2012). Freshly prepared bovine corneas were obtained from slaughtered cattles at the age of 12 to 60 months were employed in the test.

The test item was applied on the cornea of a bovine eye previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 h and whose opacity was measured. The test substance was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and two hours post-incubation, opacity and permeability values were measured.

The test substance, tested in a 10% solution in olive oil, showed no effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) was 0.747. The positive control (10% sodium hydroxide solution) induced severe irritation of the cornea (IVIS score: 156.148), and the negative control (physiological chloride solution and the solvent control (olive oil) showed no irritating effect the cornea.

On the basis of the test findings it can be concluded that the test item under the experimental condition displayed no corrosion or severe irritation potential.

In addition, acute eye irritation of the test substance was assessed by means of an in vivo study carried out according to the OECD guideline OECD 405 and GLP conditions (Colas, 2013). 0.1 mL of the test material was applied as a single treatment to the eyes of three New Zealand white rabbits each.

The animals were observed over three days. Eye irritation was scored by mean of the Draize scoring system at the following reading time points: 1, 24, 48 and 72 h. Slight to moderate and totally reversible conjunctiva reactions observed during the study have been observed: a moderate redness was noted 1 h after the treatment in all the animals and reversed within three days after treatment. In addition, slight chemosis was observed 1 hour after application in two animals. This effect resulted to be reversible on day 1. As the slight irritating effects are below the hazard classification limit, the substance is assumed as not irritating to the eye.

Based on these findings, the test material is not considered irritating to the eyes under the conditions of this study.

CAS 78-16-0

There are five eye irritation studies available for 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (CAS 78-16-0).

The first study was conducted according to EU Method B.5 and under GLP. The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits (Weterings, 1987). The animals were observed for 72 h and reactions were assessed 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. 1 h after exposure all three animals showed redness of the conjunctivae, which had disappeared the next day in all animals. Adverse effects on the cornea and the iris were not observed. Treatment with fluorescein 24 h after instillation of the test substance did not reveal any epithelial damage.

The second study was performed comparable to OECD Guideline 405 (Robinson, 1991). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three male New Zealand White rabbits. The animals were observed for 5 days and reactions were assessed 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. No effects on the cornea and the iris were observed. Conjunctival effects included slight to moderate redness and slight to severe discharge. The mean conjuctivae score out of all three animals over 24, 48 and 72 hours was 0.3. No chemosis was seen. Additional signs of irritation included erythema and dried secretion on the upper and lower eyelids and convoluted eyelids. All effects had completely reversed 4 days after application.

Three studies were conducted according to the “16 CFR 1500.42” guideline. The first one was performed by Morgareidge (1974) and examined eye irritation after instillation of 0.1 mL of undiluted test substance into the eyes of 6 albino rabbits each. Observations were made 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. Slight redness of the conjunctivae was observed after 24 hours in 3 animals and after 48 hours in 4 animals. The effect was fully reversible in all animals within 72 hours. Slight chemosis of the conjunctiva of one animal was detected after 24 hours. The effect was fully reversible within 48 hours. The mean conjuctivae and chemosis scores out of all six animals over 24, 48 and 72 hours were 0.4 and 0.1 respectively. The second study was performed by Moreno (1977) and was conducted using 6 New Zealand White rabbits. 0.1 mL undiluted test substance was instilled in the conjunctival sac of one eye of each rabbit and reactions were observed 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. Only slight conjunctival redness and chemosis (maximal score of 1) were observed which were fully reversible within 72 and 48 hours, respectively. The mean conjuctivae and chemosis scores out of all six animals over 24, 48 and 72 hours were 0.3 and 0.2 respectively.

A further (Anonymous, 1978) summary of the results is available. 0.1 mL of the undiluted test substance was applied into the conjunctival sac of 6 rabbits (strain not specified) and readings were conducted after 1, 24, 48 and 72 hours. After 24 h, one animal showed slight redness of the conjunctivae. This effect was reversible within 48 h. No other effects were observed at any reading time point. The mean conjuctivae score out of all six animals over 24, 48 and 72 hours was 0.1.

In summary, 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate is not considered to reveal eye irritating properties.

CAS 97281-24-8

Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane (CAS 97281-24-8) was tested for its acute eye irritation potential in a study performed similar to OECD Guideline 405 and in compliance with GLP (Kästner, 1988). 0.1 mL of the neat test material was applied as a single treatment without subsequent washing to the eyes of four male Chbb:HM rabbits each. The animals were observed for 72 hours and reactions were assessed 1, 6, 24, 48, and 72 hours after instillation according to the Draize scoring system. Slight conjuctival reactions were observed between 1-6 hours after treatment. They consisted of redness (4/4 animals within the first hour after treatment, 3/4 within 6 hours after treatment) and exudation (4/4 animals within the first hour after treatment). However, these reactions were fully reversible within 24 hours after treatment. Based on these findings, the mean cornea, iris, conjunctivae, and chemosis scores over 24, 48, and 72 h were zero. Thus, the test material is not considered irritating to the eyes under the conditions of this study.

CAS 11138-60-6

A second study was conducted analogously with Fatty acids, 8-10 (even numbered), di- and triesters with propylidynetrimethanol (CAS #11138-60-6).The substance was tested for eye irritation potential according to OECD Guideline 405 (Oleon, 1990), 0.1 mL of the test material were instilled into the conjunctival sac of one eye of three New Zealand White rabbits. Animals were observed for 72 hours and observed effects were scored 24, 48 and 72 hours after instillation according to 84/499/EEC appendix V B5 (Draize). No effects, except for one animal with a very slight exudation reaction at the 24 h time point, were observed in any of the tested animals at any relevant observation interval.

 

CAS 403507-18-6

Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS 403507-18-6) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Sanders, 2002). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 2 male and 1 female 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. No corneal or iridal effects occurred during the study. Moderate conjuctival irritation was observed in all treated eyes one hour after application. Minimal conjuctival irritation was noted in two treated eyes (2/3 animals) at the 24 h observation time point. The mean conjunctivae scores over 24, 48 and 72 hours were 0.33 and 0for animal #1 and #2 and 0 for animal ##3. Thus, the test material is not considered irritating to the eyes in this study.

CAS 91050-90-7

Fatty acids, C16-18, triesters with trimethylolpropane (CAS 91050-90-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (Steiling, 1989). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three male Kleinrussen, Chbb rabbits each. 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. No effects were observed except redness of the conjuctivae of grade 1 in all 3 animals at reading time point 1 h only. In 2 cases this was accompanied by exudation. These effects disappeared within 24 h. Thus, the test material is not considered irritating to the eyes in this study.

CAS 85116-93-4

Fatty acids, C16-18 (even numbered), esters with pentaerythritol (CAS 85116-93-4) was tested for its acute eye irritation potential in a study performed according to OECD Guideline 405 under GLP conditions (Steiling, 1991). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three male Kleinrussen, Chbb:HM rabbits each. 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. No effects were observed except a very mild and reversible exsudation reaction in one of three animals 24 h after application. Thus, the test material is not considered irritating to the eyes. 

CAS 67762-53-2

Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Zolyniene, 1997). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 3 (1 male, 2 female) New Zealand White rabbits each. The animals were observed for 3 days and reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. One animal exhibited moderate conjunctival redness and two animals showed mild conjuctival redness. All three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 hour post treatment, one animal was free of conjuctival redness. All three animals were free of ocular irritation within 72 hours of treatment. The mean conjunctivae score out of all three animals over 24, 48 and 72 hours was 0.67. Thus, the test material is not considered irritating to the eyes in this study.

CAS 68424-31-7

Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Robinson, 1991d). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits each. The animals were observed for three days and reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 hour after dosing. Thus, the test material is not considered irritating to the eyes in this study.

CAS 68441-68-9

There are two in vitro eye irritation studies available for Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS 68441-68-9). For both studies only limited reporting is available. The test substance was investigated for its eye corrosion potential in vitro in a HETCAM assay (Boue-Grabot, 2004). The chorioallantoic membranes of chicken eggs were exposed to the test substance. The irritation score was reported to be 0. Thus, the test material is not considered corrosive to the eyes in this test. The second study investigated the test substance for its cytotoxicity in fibroblasts (Boue-Grabot, 2004). The Ocular Irritation Index in fibroblasts (IOeq) based on cytotoxicity was found to be 0.5. Since no data are given on interpreting this index the result is considered to be inconclusive.

CAS 85586-24-9

There is one study available which was conducted with Fatty acids, C8-10, tetraesters with pentaerythritol (Kästner, 1981). The study performed without following any guideline. One eye of two male New Zealand rabbits each was exposed to 0.1 mL of the test substance (10% or undiluted) for 10 seconds followed by washing or for 48 hours without washing. Only slight irritation effects were reported but not further specified. However, since no irritation score were given, interpretation of the results in regard to classification is not possible and the study result is considered to be inconclusive.  

CAS 62125-22-8

Three eye irritation studies were conducted to assess the eye irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8).

In a HETCAM assay the test substance was tested for its eye corrosion potential in vitro under GLP (Hendricks and Nitka, 2005). The chorioallantoic membranes of 4 White Leghorn chicken eggs were exposed to 0.3 mL of the test substance as 10, 20 and 30% dilutions each for 20 seconds. The reactions of the CAM, the blood vessels, including the capillaries, and albumin were examined and scored for irritant effects. Reactions of hyperaemia, minimal haemorrhage (feathering), haemorrhage (obvious leakage) and coagulation and/or thrombosis were graded from 0=no reaction to 32=severe reaction. The numerical, time dependent scores were summed for each egg and each reaction type can be recorded only once for each egg. Irritation scores of 1.25, 2.5, 3 and 1.75 were recorded for corn oil and the test substance at10, 20 and 30% concentration, respectively. Thus, the test material is not considered corrosive to the eyes in under the conditions of this test.  

In a first in vivo study performed comparable to OECD Guideline 405 (Haynes, 1982) the undiluted test material (0.1 mL) was applied into the conjunctival sac of six female New Zealand White rabbits each. 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. 24 h after exposure, chemosis was observed in 4 of 6 animals, which disappeared the next day. All 6 animals showed redness of the conjunctivae, which disappeared in three animals the next day. At 72 h observation, redness was still observed in two animals. Since the observation was stopped after 72 h, there is no information on the reversibility of these effects in the remaining two animals. The mean conjuctivae and chemosis score out of all six animals over 24, 48 and 72 hours were 0.78 and 0.22 respectively. Adverse effects on the cornea and the iris were not observed in any of the animals. Thus, the test material is not considered irritating to the eyes in this study. 

In a second in vivo study performed comparable to OECD Guideline 405 (Bouffechoux, 1997) the test material was applied into the conjunctival sac of three male New Zealand rabbits each. The animals were observed for 72 hours and reactions were assessed 1, 24, 48, 72 hours and 7 days after instillation according to the Draize scoring system. All animals showed slight effects on the conjunctiva 1 hour after removal of the test substance. This effect lessened but was still visible for 2 animals 24 hours later but fully reversible thereafter. The mean conjuctivae score over 2 animals was 0.11, and 0 for the remaining animal. Thus, the test material is not considered irritating to the eyes in this study. 

CAS 189200-42-8

Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (Frank, 1995). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 6 (5 male and 1 female) New Zealand White rabbits each. The animals were observed for 7 days and reactions were assessed 1, 24, 48, 72 hours and 7 days after instillation according to the Draize scoring system. One hour after instillation of the test substance, slight conjunctival redness and chemosis were observed in all animals. Chemosis was reversible within 24 hours whereas conjunctival redness was reversible in all animals within 7 days. The mean conjuctivae score out all six animals over 24, 48 and 72 hours was 0.44. Fluorescein staining of the cornea was observed in three animals at the 48 h reading time point. At the 72 h reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient. Thus, the test material is not considered irritating to the eyes under the conditions of this study. 

Conclusion for skin and eye irritation

Based on the results of the available studies, none of substances within the polyol esters category is considered skin irritating. Therefore, on the basis of these findings, no classification for skin irritation for all substances within the fatty acid polyol esters category is required.

Several acute eye irritation studies have been performed in rabbits in vivo. None of the polyol esters showed an eye irritation potential. Therefore, no classification for eye irritation for all substances within the polyol esters category is required.

 

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint".

Since the category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis.

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