Sucrose, glycerol and propane-1,2-diol, reaction products with C16-18(even numbered) fatty acids

Endpoint summary

Description of key information

Grilloten PSE 141 G (25% in water) was established to be not irritating to the skin. The source substance Sucroglyceride C12 -18, C18unsatd. is not irritating to the skin following in vitro application to RHE, the relative absorbance being 87,5 % (classification is required at 50% or below).
Grilloten PSE 141 G was established to be not irritating to the eye. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

other: HLD protocol number P 2/152, revision 5. to meet the requirements of the US Food and Drug Administration as described in the "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics" (1995).

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The test item was topically applied under occlusive dressing to intact and abraded skin sites on the back of rabbits once only for a contact period of 24 hours.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H. Fortkamp, D-4540 Lengerich
- Age at study initiation: between 11 and 17 weeks
- Weight at study initiation: between 2.78 and 3.38 kg
- Housing: single housing in steel grid floor cages
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): free access
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23°C
- Humidity (%): 40 - 70 %
- Air changes (per hr):at least 10 air chamges per hour
- Photoperiod (hrs dark / hrs light): 12 /12 hours

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 25 % in water

TEST SITE: Intact and abraded skin

Duration of treatment / exposure:

24 hours

Observation period:

25 hours and 72 hours after treatment

Number of animals:

6 male rabbits

Details on study design:

TEST SITE
- Area of exposure: about 2.5 x 2.5 cm
- Type of wrap if used: unabraded and abraded skin sites were covered with gauze pads which were the occluded and secured using a strip of impermeable adhesive plastic dressing wrapped around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was wiped but not rinsed with a disposable paper towel


Reactions were scored according to the Draize scale.

SCORING SYSTEM:
Erythema and eschar formation:
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well-defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (deep redness): 4

Oedema formation:
- No oedema: 0
- Very slight oedema (barely perceptible): 1
- Slight oedema (edges of area well-defined by definite raising): 2
- Moderate oedema (raised approx. 1 mm): 3
- Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

0.33

Max. score:

8

Reversibility:

fully reversible

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this study, Grilloten PSE 141 G (25% in water). was established to be not irritating to the skin.

According to the criteria of OECD GHS, Regluation (EC) 1272/2008 and of DSD (Directive 67/548/EEC), and no classification and labelling is required.

Executive summary:

In a primary dermal irritation study 6 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of Grilloten PSE 141 G (25 % in water) for 24 hours to 2.5 x 2.5 cm of body surface area. Animals then were observed for 72 hours. Irritation was scored by the method of Draize.

The study is comparable to a guideline study (OECD 404) with some minor deviations (exposure time 24 h, readings at 24 and 72 h), which do not influence the results of the study.

The test material produced minimal irritation in 3/6 rabbits at the intact sites of five rabbits and abraded site at the 24 hours reading. The reactions had ameliorated completely in all three rabbits by the 72 hours observation.

The test item is considered to be non-irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.42

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: H.Schriever, D-2740 Bremervörde
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 20 °C
- Humidity (%):-
- Air changes (per hr):-
- Photoperiod (hrs dark / hrs light):12/12 hours

Vehicle:

water

Remarks:

aqua dest.

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.: 100 mg neat after been pesteled in mortar
2. : 0.1 ml of a 50 % suspension in aqua dest.

Duration of treatment / exposure:

no washing

Observation period (in vivo):

24h, 48h, 72h, 7d

Number of animals or in vitro replicates:

2 x 6 rabbits

Details on study design:

The test item was placed into the conjunctival sac of one eye, while the second eye was used as a control.
Ocular reactions were assessed 24, 48 and 72 h as well as 7 days after treatment.

REMOVAL OF TEST SUBSTANCE
- no

SCORING

According to "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics published by the Food and Drug Officials of the United States, 1959".
I.) Cornea opacity Value
No opacity 0
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Complete corneal opacity, iris not discernible 4

I.) Cornea area Value
One quarter (or less) but not zero 1
Greater than one quarter, but less than one half 2
Greater than one half, but less than three quarters 3
Greater than three quarters, up to whole area 4

II.) Iris Value
Normal 0
Folds above normal, congestion, swelling, moderate circumcorneal injection
(any of these or any combination of them), iris still reacting to light 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

III.) Conjunctivae redness Value
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

III.) Conjunctivae chemosis Value
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to complete closed 4

III.) Conjunctivae discharge Value
No discharge 0
Any amount different from normal ( does not include small amounts
observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to the lids 2
Discharge with moistening of the lids and hairs and affecting a considerable
area around the eye 3


The Irritation Index was calculated from the numerical scores for cornea, iris and conjunctivae according to the following scheme:

I.) Cornea: opacity x area x 5 maximum 80
II.) Iris: iris x 5 maximum 10
III.) Conjunctivae: (redness + chemosis + discharge) x 2 maximum 20
sum = maximum 110

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 days

Score:

4.3

Max. score:

110

Reversibility:

fully reversible

Remarks on result:

other: result for the neat test item

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 days

Score:

2.1

Max. score:

110

Reversibility:

fully reversible

Remarks on result:

other: result for the 50 % suspension in aqua dest.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In this study the test substance is not irritating to the eye. According to the criteria of OECD GHS, Regluation (EC) 1272/2008 and of DSD (Directive 67/548/EEC) no classification and labelling is required.

Executive summary:

In a primary eye irritation study similar to OECD Guideline 405 0.1g of Grilloten PSE 141 neat or 0.1 ml of a 50 % suspension in water was instilled into the conjunctival sac of one eye, each of six New Zealand White rabbits. The eyes were not washed. Animals were then observed for 7 days.

Instillation of the test substance resulted in slight to moderate irritation of the conjunctivae, which consisted of redness and chemosis. The irritation completely resolved within 7 days.

In this study, Grilloten PSE 141 is not an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Assessment of skin irritation / corrosion

 

Key study on the registration substance Sucroglyceride C16-18 25% a.i. (Evonik, 1984)

In an in vivo study, a paste of Sucroglyceride C16-18 10% a.i. was tested. The test substance is a white paste. Purity is 25% a.i.

A primary dermal irritation study was performed according to HLD protocol number P 2/152, revision 5. The study design is in principle comparable to a guideline study (OECD 404) with some deviations. Treatment was on intact and abraded skin, exposure time was 24 h, readings were performed at 24 and 72 h.

0.5 mL of Sucroglyceride C16-18 25% a.i. were administered under occlusive dressing to intact and abraded skin segments, to 2.5 x 2.5 cm of the body surface area, of 6 young adult New Zealand White rabbits. The duration of exposure was 24 h, animals then were observed for 72 hours and skin reactions were scored by the method of Draize.

On intact skin, edema scores for all animals were 0 at the 24 and 72 h readings while the erythema score was 0 for three animals and 1 for three animals at the 24 h reading and 0 for all animals at 72 h.

On the abraded skin, edema scores were 0 for all animals at the 24 and 72 h reading, while the erythema score was 0 for one animal and 1 for five animals at the 24 h reading and 0 for all animals at 72 h.

Thus, all dermal reactions were completely reversible after 72 h and in no case the edema or erythema scores obtained for Sucroglyceride C16-18 25% a.i. reached the threshold which would require classification. Sucroglyceride C16-18 25% a.i. is graded as not irritant to the skin.

 

 Supporting study on the read-across substance Sucroglyceride C12-18, C18unsatd. (Evonik, 2011)

For the examination of skin irritation, Sucroglyceride C12-18, C18unsatd. was tested in vitro on Reconstructed Human Epidermis (RHE). The test substance is a waxy solid. Purity is 100% or 91-94%, respectively, by subtraction of the water content.

In an in vitro Human Skin Model Test, performed according to the OECD Test Guideline 439, the potential to cause irritation upon first contact with the skin was assessed by application of the test substance to RHE. 10 mg of the Sucroglyceride C12 -18, C18unsatd. were applied together with 15μL of water to an area of approximately 0.38 cm² of RHE and incubated for 15 min.

For evaluation of the potential of the test substance to cause skin irritation, the samples of treated reconstituted skin were then exposed to MTT for 3 h. The potential to reduce MTT and form a blue Formazan salt was assessed by extraction of Formazan over 69 h and subsequent determination of its absorbance at 570 nm.

The positive control, a 5 % solution of SLS (Sodium lauryl sulphate) in water, resulted in a mean relative absorbance of 33.0%, the negative control value was 100%. Treatment with the test substance resulted in a mean relative absorbance of 87.5%.

In this test system, the threshold for considering a substance as irritant is a mean relative absorbance ≤ 50%. Thus, Sucroglyceride C12 -18, C18unsatd. is graded as not irritant to the skin.

 

Supporting study on the read-across substance Stearic acid, esters with methylα-D-glucoside (Evonik, 1990)

The read-across substance Stearic acid, esters with methylα-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its dermal irritation potential. The test substance is a solid. Purity is 100%.

In a primary dermal irritation study according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion), three New Zealand White rabbits were dermally exposed to 0.5 mL of Stearic acid, esters with methylα-D-glucoside. The test substance was applied for 4 hours to intact shaved body surface areas of approximately 6 cm² under semi-occlusive dressing. Animals then were observed for 72 hours. Irritation was scored by the method described in OECD Guideline 404.

Edema scores and erythema scores were 0 for all animals after 30-60 min and after 24, 48 and 72 hours.

Thus, Stearic acid, esters with methylα-D-glucoside is graded as not irritant to the skin.

 

Supporting study on the read-across substance Isostearic acid, esters with methylα-D-glucoside (Evonik, 2009)

The read-across substance Isostearic acid, esters with methylα-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its dermal irritation potential. The test substance is a yellow paste. Purity is 100%.

In a primary dermal irritation study according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion), three young adult male New Zealand White rabbits were dermally exposed to 0.5 g of Isostearic acid, esterswith methylα-D-glucosideas supplied by the sponsor for 4 hours, under semi-occlusive dressing. The animals then were observed for 14 days. Irritation was scored by the method described in the OECD Guideline 404.

Very slight erythema in the treated skin areas of all three animals was observed after 60 minutes, which had resolved within 24 h after exposure in two animals and within 7 days after exposure in one animal. Scaliness in the treated skin area of one animal was noted at 72 hours and 7 days post-treatment and had resolved within 14 days.

Edema scores were 0 for all animals after 30-60 min and after 24, 48 and 72 h.

Erythema scores were 0 for two animals and 1 for one animal after 24 h and 0 for all animals after 48 and 72 h.

Thus, all dermal reactions were completely reversible after 72 h and in no case the edema or erythema scores obtained for Isostearic acid, esters with methylα-D-glucoside reached the threshold which would require classification. Isostearic acid, esters with methylα-D-glucoside is graded as not irritant to the skin.

 

General evaluation of skin irritation / corrosion

 

A paste containing 25% a.i. of Sucroglyceride C16-18 is not irritant following 24 h exposure to intact and abraded skin. The overall evaluation of these data allow to conclude that Sucroglyceride C16-18 is not a skin irritant. 

 

The read-across substance Sucroglyceride C12-18, C18unsatd. is not irritant in an in vitro assay.

 

For dermal irritation / corrosion, the registration substance Sucroglyceride C16-18 and the three read-across substances Sucroglyceride C12-18, C18unsatd., Stearic acid, esters with methylα-D-glucoside and Isostearic acid, esters with methylα-D-glucoside exhibit a comparable profile and are characterised by experimental results which lead to the same overall evaluation with regard to classification and labelling.

 

For the registration substance Sucroglyceride C16-18 and for three read-across substances, the dermal irritation potential is very low or absent after a single dermal administration.

 

Based on the experimental evidence provided for skin irritation / corrosion, Sucroglyceride C16-18 does not need to be classified for skin irritation according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC) and labelling is not required.

 

 

Assessment of eye irritation

 

Key study on the registration substance Sucroglyceride C16-1866. (Evonik, 1983)

In order to assess its potential for eye irritation, Sucroglyceride C16-18 was tested in an in vivo study. The test substance is a white waxy solid. Purity is 100%.

A primary eye irritation study was performed according to Code of Federal Regulations, Title 16, Section 1500.42. The study design is in principle comparable to a guideline study (OECD 405). The eye irritation potential of the test substance was assessed after a single application to rabbit eye for 24 hours. The animals were observed for evidence of irritation at 24-48-72 h post application. Reactions were scored according to the scale of Draize.

0.1 mL (100 mg) of Sucroglyceride C16-18 was instilled undiluted into the conjunctival sac of one eye of 6 young adult New Zealand White rabbits. And additionaly 0.1 ml of a 50% suspension of Sucroglyceride C16-18 in aqua dest. was instilled into the conjunctival sac of one eye of further 6 young adult New Zealand White rabbits. Eyes were not washed. Animals were then observed for 7 days. Irritation was scored by the method of Draize.

Instillation of the test substance resulted in slight to moderate irritation of the conjunctivae, which consisted of redness and chemosis. The irritation completely resolved within 7 days.

 

Thus, all observed ocular effects were completely reversible within 72 h. Both treated eyes appeared normal and in no case the Draize scores obtained for Sucroglyceride C16-18 reached the threshold which would require classification. Sucroglyceride C16-18 is graded as not irritant to the eye.

 

Supporting study on the registration substance Sucroglyceride C12-18, C18unsatd. (Evonik, 2012)

In order to assess its potential for eye irritation, Sucroglyceride C12-18, C18unsatd. was tested in an in vivo study. The test substance is a white waxy solid. Purity is 100% or 92.66%, respectively, by subtraction of the water content.

A primary eye irritation study was performed according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion). In this study, eye irritation was tested on only two rabbits rather than three since the eye irritation scores of the two animals were identical. In the absence of differences in the irritation scores of the two rabbits, and for animal welfare reasons it is the default of the testing facility to avoid the use of a third animal. In fact, on the basis of the results obtained, it is not to be expected that treating a third rabbit would have modified the study outcome and the indications for classification and labelling.

0.1 mL (99 mg) of Sucroglyceride C12-18, C18unsatd. was instilled undiluted into the conjunctival sac of one eye of 2 young adult New Zealand White rabbits. Eyes were not washed. Animals were then observed for 72 hours. Irritation was scored by the method of Draize.

Scattered or diffuse corneal opacity and iridial inflammation was observed in both treated eyes 1 h after treatment. Moderate conjunctival irritation was noted in both treated eyes a 1 and 24 h after treatment with minimal conjunctival irritation noted at the 48 h observation.

For both animals the cornea score was 1 after 1 h and 0 at 24-48-72 h, the iris score was 1 after 1 h and 0 at 24-48-72 h, the conjunctivae score was 2 at 1-24 h, 1 at 48 h and 0 at 72 h, the chemosis score was 2 at 1 h, 1 at 24-48 h and 0 at 72 h, the discharge score was 2 at 1 h, 1 at 24 h and 0 at 48-72 h.

Thus, all observed ocular effects were completely reversible within 72 h. Both treated eyes appeared normal and in no case the Draize scores obtained for Sucroglyceride C12-18, C18unsatd. reached the threshold which would require classification. Sucroglyceride C12-18, C18unsatd. is graded as not irritant to the eye.

 

Supporting study on the read-across substance Stearic acid, esters with methylα-D-glucoside (Evonik, 1990)

The read-across substance Stearic acid, esters with methylα-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its ocular irritation potential. The test substance is a solid. Purity is 100%.

A primary eye irritation study was performed according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion). In this study, eye irritation was tested on three rabbits.

0.1 g of Stearic acid, esters with methylα-D-glucoside was instilled undiluted into the conjunctival sac of one eye of three New Zealand White rabbits. The untreated eye served as control. The eyes were not washed. Animals were then observed for 72 hours. Irritation was scored as stipulated by OECD Guideline 405.

No iridial irritation or corneal opacity was observed. An irritation of the conjunctivae, which consisted of redness and chemosis was observed in one eye of each rabbit within the first hour. The irritation was fully reversible within 24 hours.

The cornea score was 0 for all animals at 1-24-48-72 h, the iris score was 0 for all animals at 1-24-48-72 h, conjunctivae score was 0 for all animals at 24-48-72 h, chemosis score was 0 for all animals at 24-48-72 h.

Thus, the minor ocular effects observed were completely reversible within 24 h. In no case the Draize scores obtained for Stearic acid, esters with methylα-D-glucoside reached the threshold which would require classification. Stearic acid, esters with methylα-D-glucoside is graded as not irritant to the eye.

 

Supporting study on the read-across substance Isostearic acid, esters with methylα-D-glucoside (Evonik, 2009)

The read-across substance Isostearic acid, esters with methylα-D-glucoside, a structural analogue of the registration substance, was tested in vivo for its ocular irritation potential. The test substance is a yellow paste. Purity is 100%.

In a primary eye irritation study according to OECD Guideline 405 0.1 mL of Isostearic acid, esterswith methylα-D-glucoside, was instilled into the conjunctival sac of one eye, each of three New Zealand White rabbits. The eyes were not washed. Animals were then observed for 72 hours. Irritation was scored according to OECD Guideline 405.

After 1 h, instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness (score 1). The irritation completely resolved within 24 hours.

The cornea score was 0 for all animals at 1-24-48-72 h, the iris score was 0 for all animals at 1-24-48-72 h, conjunctivae score was 1 for all animals at 1 h and 0 for all animals at 24-48-72 h, chemosis score was 0 for all animals at 1-24-48-72 h, discharge score was 0 for all animals at 1-24-48-72 h.

Thus, the minor ocular effects observed were completely reversible within 24 h. In no case the Draize scores obtained for Isostearic acid, esters with methylα-D-glucoside reached the threshold which would require classification. Isostearic acid, esters with methylα-D-glucoside is graded as not irritant to the eye.

 

General evaluation of eye irritation

Sucroglyceride C16-18 is not irritant to the eye performed on pure substance and on 50% a.i. The overall evaluation of these data allow to conclude that Sucroglyceride C16-18 is not an eye irritant.

 

For ocular irritation, the registration substance Sucroglyceride C16-18 and the three read-across substances, Sucroglyceride C12-18, C18unsatd, Stearic acid, esters with methylα-D-glucoside and Isostearic acid, esters with methylα-D-glucoside exhibit a comparable profile and are characterised by experimental results which lead to the same overall evaluation with regard to classification and labelling.

 

For the registration substance Sucroglyceride C16-18 and for three read-across substances, the ocular irritation potential is extremely low or absent after a single ocular administration.

 

Based on the experimental evidence provided for ocular irritation, Sucroglyceride C16-18 does not need to be classified for eye irritation according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC) and labelling is not required.

Justification for selection of skin irritation / corrosion endpoint:
In the key study, an vivo test, Sucroglyceride C16-18 (25% a.i.) was used.
Only the read-across in vitro study was performed on concentrated Sucroglyceride C12-18, C18unsatd.

Justification for classification or non-classification

With respect to skin irritation / corrosion the in vivo result for the test substance and the in vivo and in vitro read-across data from four studies with chemically closely related substances show that edema and erythema scores are very low or absent and that there is no skin irritation potential. Consequently, unambiguous data are available to support that, according to the CLP Regulation (EC) No 1272/2008 and according to DSD (67/548/EEC), there is no need for classification of Sucroglyceride C16 -18 for skin irritation / corrosion and no labelling is required.

Furthermore, with respect to eye irritation the in vivo results for the test substance and the in vivo read-across data from three studies with chemically closely related substances show that scores for cornea, iris, conjunctivae, chemosis and discharge are very low or absent and that there is no eye irritation potential.

Consequently, unambiguous data are available to support that, according to the CLP Regulation (EC) No 1272/2008 and according to DSD (67/548/EEC), there is no need for the classification of Sucroglyceride C16 -18 for eye irritation and no labelling is required.