Fatty acids, C16-18 and C18-unsatd., Me esters, epoxidized, reaction products with ethylene glycol

Endpoint summary

Description of key information

No data on skin and eye irritation are available for the substance itself. Analogues were investigated in vitro and/or in vivo in rabbits for their skin and eye irritation/ corrosion potential according to international accepted guidelines. With regard to skin irritation, the test items were considered to be not irritating. Considering eye irritation, the test items were judged to be slightly irritating, but without fulfilling the criteria for classification.

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:

1998/06/03- 1998/07/04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material: SAT 980403, Soj amethylesterepoxid TMP ring geöffnet, Sovermol 760
- Physical state: clear, colourless, viscous liquid
- Analytical purity: 90 %
- Expiry date: Jan 1999
- Lot/batch No.: 18009
- Storage condition of test material: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: E.A. Prinzhom, Altenbücker Damm 28, 27333 Altenbücken, Germany
- Weight at study initiation: > 2.5 kg
- Housing: The rabbits were kept individually in a battery of cages with a cage size of 50 x 45 x 40 cm (L x B x H), equipped with a paper disposal system.
- Diet: "Harlan Teklad TLM Rabbit Maintenance Diet" pelleted breeding diet produced by Harlan Teklad, Shaw's farm, Blackthom Bicester, Oxon, OX6 OTP, England
- Water: community tap water
- Acclimation period: > 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity: 30- 70 %
- Air changes: 16/ hour
- Photoperiod: cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: undiluted

Duration of treatment / exposure:

4 hours

Observation period:

Skin reactions were assessed 1, 24, 48 and 72 h after the end of the exposure.

Number of animals:

2 males
1 female

Details on study design:

TEST SITE
- Type of wrap if used: semiocclusive bandage, Ypsiplast® (Holthaus Medical, Remscheid-Lüttringhausen), nonirritating tape Elastoplast® (Beiersdorf AG, Hamburg) and Stülpa® (P. Hartmann AG, Heidenheim-Brenz), which enveloped the whole ofthe animal's trunk.

SCORING SYSTEM:
Skin reactions were graded based on the calculated mean values as stipulated by OECD 404:

Erythema and Eschar Formation
0 Non erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

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

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Irritant / corrosive response data:

Mean values of skin reactions at 24, 48 and 72 h after exposure (test side)
animal 1: 1.67 (erythema); 0.67 (oedema)
animal 2: 2.00 (erythema); 0.67 (oedema)
animal 3: 1.33 (erythema); 0.67 (oedema)

Interpretation of results:

GHS criteria not met

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:

1998/06/26- 1998/07/02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material: SAT980403
- Physical state: clear, colourless, viscous liquid
- Analytical purity: 90 %
- Lot/batch No.: 18009
- Expiration date of the lot/batch: January 1999
- Storage condition of test material: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: E.A. Prinzhom, Altenbücker Damm 28, 27333 Altenbücken, Germany
- Weight at study initiation: > 2.5 kg
- Housing: The rabbits were kept individually in a battery of cages with a cage size of 50 x 45 x 40 cm (L x B x H), equipped with a paper disposal system.
- Diet: Harlan Teklad TLM Rabbit Maintenance Diet pelleted breeding diet produced by Harlan Teldad, Shaw 's fann, Blackthom Bicester, Oxon, OX6 OTP, England
- Water: community tap water
- Acclimation period: > 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity: 30 - 70 %
- Air changes: 16/ hour
- Photoperiod: Artificiallight was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: undiluted

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment

Number of animals or in vitro replicates:

1 male
2 females

Details on study design:

SCORING SYSTEM:
Ocular reactions were assessed 1, 24, 48 and 72 h after treatment according to the grades for ocular lesions as stipulated in the OECD 405

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Slight to moderate redness and swelling of the conjunctivae associated with slight ocular secretion were observed in all animals 1 h after instillation. Slight redness and swelling were seen in all animals at 24 h post application. Slight redness was apparent in one animal up to 48 h after instillation. In two of three animals vascular injection on the eyeball was observed at 1 h after instillation.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No studies on skin or eye irritation are available for the substance itself. Therefore, data on structurally related substances is used. Summaries of these studies are provided below.

Skin irritation/ corrosion (CAS 188831-96-1):

The skin irritating toxicity of the test item was assessed in an acute dermal irritation/corrosion test in 3 albino rabbits according to OECD 404, adopted in 1992. In this key study, 0.5 mL of the test item was applied on the right side of the clipped back, the untreated left side served as control. Exposure duration was 4 h. Both sides were examined at 1, 24, 48 and 72 h after the end of exposure and thereafter until reversibility of the findings. Well-defined to very slight erythema and very slight oedema were observed in all animals at 1 h after the 4-hour exposure and disappeared within 4 to 8 days after exposure. No other toxic effects were observed. The mean grades of skin reactions at 24, 28 and 72 h after the end of the exposure were, in the three animals with 1.67, 2.0 and 1.3 for erythema and 0.67 for oedema formation, lower than the value classified as irritant by the EEC Directive 93/21/EEC. Therefore the test item was classified as "non-irritant" when applied to skin (Toxlabs Bioscience GmbH 1998).

 

Skin irritation/ corrosion (CAS 85586-35-2):

The skin irritation potential of the test item was assessed by a single topical application of an amount of 0.5g of the test item for 4 hours to the intact skin of three White New Zealand rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After patch removal the application area was washed off. The cutaneous reactions were assessed immediately after patch removal, approximately 1, 24, 48 and 72 hours after patch removal and in weekly intervals until day 14. Mean scores over 24, 48 and 72 hours for each animal were 1.3, 2.0 and 0.7 for erythema and 0.0, 0.0 and 0.0 for edema. The cutaneous reactions were reversiböe in all animals within 14 days at the latest. Considering the described cutaneous reactions as well as the average scores, the test item does not show a skin irritating potenital under the test conditions (18H0114/12X031, 2013).

Furthermore the test item was investigated in-vitro for skin corrosion and irritation. The mean viability of the treated tissues in the corrosion test after an exposure period of 3 minutes was 94% and it was 101% after an exposure period of 1 hour. The mean viability of the treated tissues in the irritation  test after an exposure period of 1 hour with about 42 hours post-incubation was 108%. Compound residues remained on the tissues after the washing procedure. However, this did not interfere with the MTT assay, as the test substance was not able to reduce MTT directly, which was demonstrated in a pretest. Based on these results it was concluded that the test substance does not show a skin irritation potential under the conditions of the test (31V0114/12A120, 2012).

 

Skin irritation/ corrosion (CAS 151661-88-0):
The test item was investigated for its skin irritating potential in vivo using rabbits according to OECD 404, adopted in 1981. 0.5 mL of undiluted test item, which was liquidized at 37 °C, were applied topically onto 6 cm² of clipped intact rabbit skin. After an exposure time of 4 hours skin reactions were evaluated over an observation period of 72 hours. The erythema and oedema score was 0 for all animals. No skin reaction was observed in any of the three animals. Therefore the test item is considered to be “not irritant” to the skin (Henkel 1989). 

 

 

Skin irritation/ corrosion (Oleic methyl ester, epoxidized, reaction products with glycerol):
The test item was tested for primary skin irritation under occlusive conditions, by application to the dorsal skin of 5 rabbits. 0.5 g of the undiluted substance was applied to a linen patch which was then fixed to the dorsal area for a period of 4 hours. After removal of the patch the skin reactions exhibited by each animal were assessed. One of the five animals showed a slight erythema 24 hours after the removal of the patches. This reaction disappeared within 24 hours. The other four rabbits did not exhibit any skin reaction. Because there was only a slight reaction and only one of the 5 animals showed a reaction at all, the substance is not classified as primary skin irritant (Henkel 1985).

 

 

Eye irritation/ corrosion (CAS 188831-96-1)

The potential irritating properties of the test item were assessed in an acute eye irritation/corrosion test in albino rabbits according to OECD 405, adopted in 1992. In this key study, 0.1 mL of the test article was introduced into the conjunctival sac of the left eye, the untreated right eye served as control. Both eyes were examined at 1, 24, 48 and 72 h post application. Slight to moderate redness and swelling of the conjunctivae were observed in all animals at 1 h after instillation and disappeared within 48 to 72 h post application. Slight ocular secretion was seen in all animals at 1 h after instillation. Two animals revealed a slight vascular injection on the eyeball at 1 h after treatment. No other toxic effects were observed. The mean grades of ocular reactions at 24, 28 and 72 h post application were in all three animals lower than the value classified as irritant by the EEC Directive 93/21/EEC (cornea score = 0; iris score = 0; chemosis = 0.33; conjunctivae score = 0.33 for animal 1 and 3 and = 0.67 for animal 2). Therefore the test item was classified as "non-irritant” (Toxlabs Bioscience GmbH 1998). This result is confirmed by data from an in vitro study in which the irritating potential of the test item was assessed using the HET-CAM test. Also here, the test item was considered to be not irritating (Henkel 1998).

 

Eye irritation/ corrosion (CAS 85586-35-2)

The potential to cause serious damage to eyes was assessed by a single topical application of 750µl of the undiluted test substance to the epithelial surface of isolated bovine corneas. Three corneas were treated with the test substance for 10 minutes followed by a 2-hours post-incubation period. Corneal opacity was measured quantitatively as the amount of light transmission through the cornea. Permeability was measured quantitatively as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were used to calculate an In Vitro Irritancy Score of the test substance relative to the control corneas.

The BCOP test showed the following results:

- Mean opacity value: 1.1

- Mean permeability value: 0.001

- in vitro irritancy score: 1.1

Based on the observed results it was concluded, that the test substance does not cause serious eye damage in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen (BCOP, 63V0114/12A122, 2012).

The potential to cause ocular irritation was assessed by a single topical application of 50 μL of the test substance to a reconstructed three dimensional human cornea model (EpiOcular™). Two EpiOcular™ tissue samples were incubated with the test substance for 30 minutes followed by a 2-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the testsubstance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The test substance is not able to reduce MTT directly. The mean viability of the test-substance treated tissues was 100%.
Based on the observed results it was concluded, that the test substance does not show an eye irritation potential in the EpiOcular™ eye irritation test under the test conditions chosen (EpiOcular, 62V0114/12A121, 2012).

 

Eye irritation/ corrosion (CAS 151661-88-0):

The test item was investigated for its eye irritating potential in vivo using rabbits according to OECD 405, adopted in 1981. 0.1 mL of undiluted test item were applied in to the conjunctival sac of the right eye. The left eye remained untreated as control. After an exposure time of 24 hours slight eye irritations such as redness and swelling of the conjunctivae were observed in all three animals. The mean cornea score for all animals over 72 hours was 0. The mean iris score for all animals over 72 hours was 0. The mean conjunctivae score for animal 1 and 3 was 0.66 and for animal 2 it was 0.33. The mean chemosis score for animal 1 and 3 was 0.33 and for animal 2 it was 0. All signs of toxicity were reversible within 48 hours. Therefore the test item is considered to be slightly irritating to the eye however without the need for classification (Henkel, 1989).

 

Eye irritation/ corrosion (Oleic methyl ester, epoxidized, reaction products with glycerol):
The substance was tested for acute eye irritation in the rabbit by single application of 0.1 g of the undiluted compound and permanent contact. The treatment provoked no reactions of the cornea and iris. In all animals moderate or strong redness and moderate or strong exudation, in some animals slight chemosis, too, could be observed one and six hours after application. 18 hours later in three animals slight redness and in two animals slight exudation were assessed only. 48 hours after the application all symptoms had disappeared in all four animals. Because there were only slight reactions 24 hours after application, the test substance is not classified as primary eye irritant (Henkel 1985).

Justification for classification or non-classification

Based on the available data classification and labeling for skin and eye irritation is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008