Glycerol, propoxylated, esters with acrylic acid

Endpoint summary

Description of key information

Skin:
Rabbit, 4h, OECD 404: No redness or oedema were observed (BASF, 1987)
Rabbit, 4h, OECD 404: Slight or moderate erythema (0.6), no edema (BASF, 2005)
Rabbit, 4h, OECD 404: No reactions observed (Cytec, 1986)
Rabbit, 4h, OECD 404: very slight erythema day 0 (1), no edema (Cytec, 1986)
Rabbit, 4h, OECD 404: No reactions observed (Cray Valley, 1993)
Rabbit, 4h, OECD 404: very slight erythema (0.1), no edema  (Cray Valley, 1995)
Eye: 
Rabbit, OECD 405: Well-defined to moderate signs (cornea opacity 1.0, iris lesion 1.0, redness of conjunctiva 2.7 and edema 2.0). Fully reversible within 14 days. (Cognis, 1999)
Rabbit, OECD 405: Slight to severe signs (cornea opacity 1.7, iris lesion 1.0, redness of conjunctiva 2.8 and edema 2.6). Fully reversible within 21 days  (BASF, 2005)
Rabbit, OECD 405: Slight to well defined signs (cornea opacity 0.9, iris lesion 0; redness of conjunctiva 1.1, chemosis 0.67). Fully reversible within 7 days (Cray Valley, 1995)
Rabbit, FIFRA: moderate to severe signs (cornea opacity 1.67, iris lesion 0.4, redness of conjunctiva 2.67 and edema 2.3). Fully reversible within 10 days (Cytec, 1984)

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

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:

24 April 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

16 June 2004

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch No.: GK0561/158
Date of production: June 08, 2004

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A., 01540 Vonnas, France
- Strain / quality: New Zealand White Al 077 INRA (SPF)
- Age at study initiation: 8 - 9 months
- Weight at study initiation:3.71 kg - 4.02 kg
- Housing:The animais were housed in fully air-conditioned rooms, in which a central air-conditioning system, Stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet (e.g. ad libitum): Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water (e.g. ad libitum):Tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%.
- Photoperiod (hrs dark / hrs light):12 h light (6.00 a.m. - 6.00 p.m.), 12h darkness (6.00 p.m. - 6.00 a.m.)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin sites of the same animal.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: The test patch (2.5 cm x 2.5 cm) was moistened with a dose of 0.5 mL of the undiluted liquid test substance.

Duration of treatment / exposure:

4h

Observation period:

1h, 24h, 48h, 72h, 7d and 14d

Number of animals:

starting with 1, increased to 3.

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap : The test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull@ stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing: substance was removed at the end of the exposure period with Lutrol and Lutrol / water (1:1)
- Time after start of exposure:4

SCORING SYSTEM: according to Draize:
Erythema and eschar formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Weil defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema: 4

Edemna formnation
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area weil defined by definite raising): 2
Moderate edema (raised approx. 1 mm): 3
Severe edema (raised more than 1 mm and extending beyond area of exposure: 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Moderate erythema (grade 2), observed in all animais immediately after removal of the patch, persisted in two animais up to 1 hour and decreased to slight (grade 1) in one animal after 1 hour. Slight erythema, noted in two animais after 24 hours, persisted in one animal up to the 48-hour reading and in the other animal up to the 72-hour reading. No other cutaneous reactions were observed during the study. The cutaneous reactions were reversible within 24 hours, 72 hours or 7 days in one animal each.

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:

26.07.1999 to 10.08.1999

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:

February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

January 1997

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Lot/batch No.: 9915159652
- Expiration date of the lot/batch: June 2000

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kißlegg
- Weight at study initiation: 1.8 kg
- Housing: individually in PPO cages (floor area: 2576 cm2) with perforated floor
- Diet ad libitum; pelleted complete rabbit diet "Altromin 2123" from Altromin, 0-32791 Lage, Lippe
- Water ad libitum; domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55% ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

Test substance was placed and first examination take place after 24h

Observation period (in vivo):

72h (1h, 24h, 48h and 72h readings)

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Remarks:

opacity degree

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Remarks:

lesion

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean of 24h, 48h and 72h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Remarks:

Oedema of conjunctiva

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Well-defined to moderate signs of irritation were observed on the treated eyes.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are valid in vivo study data available to assess the irritating potential of the test item to skin and eye.

 

Skin irritation:

In the key study (BASF, 2005) the potential of the test item to cause acute dermal irritation or corrosion was assessed according to OECD guideline 404 by a single topical application of an amount of 0.5 mL of the test substance for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and on day 7. Slight or moderate erythema was observed in all animals during the course of the study. The cutaneous reactions were reversible in all animals within 7 days after removal of the patch at latest. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.7 and 0.0 for erythema and 0.0 edema. Considering the described cutaneous reactions as well as the average score for irritation, the test item does not show a skin irritation potential under the test conditions chosen.

 

In a study (BASF, 1984) in accordance to Fed.Reg. 38, No. 187, para 1500.41 S. 27019 the acute skin irritating potential of the test item was tested at 6 vienna white rabbits. Therefore 0.5 mL of the test substance were applied to the clipped back and covered occlusively for 24h. Remaining test substance was removed and gradings were recorded 24h, 48h, 72h and 8 days after application. Moderate irritation (redness and oedema) could be observed directly after removal of the patch. The irritant effect declined towards the 72h reading. After 8 days only desquamation were observed. In to the report an irritation index of 3.3 was calculated.

 

In a study according to OECD 404 (BASF, 1987) the irritating potential of two different batches of the test item were tested with 3 rabbit each. After 4h application of 0.5 mL test item gradings were recorded after 24h, 48h and 72h. No redness or oedema were observed. No other unusual findings were recorded. Therefore the substance was considered to be not irritating.

 

In another study (Cognis, 1980) to investigate the degree of irritation produced to the abraded and intact skin of 6 albino rabbits following 24 hours occluded contact with the test material the procedure described in the U.S. Federal Register, Vol. 38, No. 187, Section 1500 : 41, 1973 was used. The average scores produced by the group of 6 rabbits were 1.2 for erythema, and 0.8 for oedema. In conclusion the sample was regarded as mild irritant to the skin of the albino rabbit.

 

A further study (Cray Valley, 1993) was performed to assess the skin irritation potential of the test item to the rabbit. The method followed was that described in EEC Methods for the determination of toxicity, Directive 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B.4. Acute toxicity (skin irritation). Three rabbits were each administered a single dermal dose of 0.5 mL of the test substance and observed for four days. No reactions were observed following a single semi-occlusive application of the test item to intact rabbit skin for four hours.

 

Another study (Cray Valley, 1995) was performed to assess the skin irritation potential of the test item to the rabbit. The method followed EEC B.4 and OECD guideline 404. Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance and observed for four days. Very slight dermal reactions were observed following a single semi-occlusive application of the test item to intact rabbit skin for four hours. The Primary Irritation Index was calculated to be 0.2.

 

In another study (Cytec, 1986) the skin irritation potential of the test item was tested according to OECD 404 with 3 rabbits. Therefore 0.5 mL of the test substance was applied under a 2.5 cm square gaze pad onto the intact (clipped) skin of the rabbit for 4h. In result none of the animals showed any observable response to treatment throughout the four days observation period. In summary a single semi-occlusive application to intact rabbit skin for four hours elicited no dermal irritation.

 

In a further study (Cytec, 1986) the skin irritation of the test item was observed according to OECD 404 with 3 rabbits. Therefore 0.5 ml aliquots were applied under a 2.5 cm square gauze pad onto the intact rabbit skin for 4h. Very slight erythema was observed in all three animals following removal of the bandages. The skins were normal after 24h. In summary, a single semi-occlusive application of the test item to intact rabbit skin for four hours elicited very slight transient dermal irritation.

 

Conclusion

Based on the available data, only slight irritations were observed immediately after removal of the patch. Therefore, the substance is considered to be not irritating to the skin.

 

Eye irritation:

In the key study (Cognis, 1999) the eye irritant effect of the test item was investigated according to OECD Guideline No. 405 and EEC Guideline B.5. Three female albino rabbits were exposed to 0.1 mL of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours as well as 7 and 14 days after dosing. Well-defined to moderate signs of irritation were observed on the treated eyes. Based on the results from the 24, 48 and 72 hour readings, the following mean values were calculated: cornea opacity 1.0, iris lesion 1.0, redness of conjunctiva 2.67 and edema 2.0. All reactions were fully reversible within 14 days.

In another BASF study (BASF, 2005) the potential of the test item to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL of the test substance to one eye of three White New Zealand rabbits according to OECD guideline 405. About 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 28. Slight or moderate corneal opacity, moderate iritis, slight to severe conjunctival redness, slight to severe conjunctival chemosis and slight to severe discharge were observed in the animals during the course of the study. Additional findings like small retraction in the eyelid, suppuration, contracted pupil, discharge of blood, loss of corneal tissue, injected scleral vessels in a circumscribed area or circular and marginal vascularization of the cornea in a circumscribed area were observed in the animals during the observation period. All ocular reactions were reversible within 21 days at the latest. The average score (24 to 72 hours) for irritation was calculated to be 1.7 for corneal opacity, 1.0 for iris, 2.8 for conjunctival redness and 2.6 for chemosis.

 

The acute eye irritation of the test item was tested according to OECD 405 (BASF, 1987). Three white rabbits received 0.1 mL undiluted test item each. Slight effect at the cornea (grading 1), slight signs of iritis (only in 24h reading), well defined conjunctivae redness and slight to severe chemosis could be observed. Within 21 day of investigation some effects already survived/increases (opacity increased from grading 1 to 2 or 3). This increase in corneal opacity from day 3 to day 8 is very unusual, and it can be assumed that this effect is not substance specific. Therefore based on this finding and in combination with several other studies available where no serious eye damage was observed, the study was rated as less reliable and the increase and irreversible effect was assumed as not substance related.

 

In another study (Cray Valley, 1995) to assess the eye irritation potential of the test item according to EEC Guideline B.5 and OECD Guideline 405 three rabbits were each administered a single ocular dose of 0.1 ml of the test substance and observed for seven days after instillation. A single instillation into the eye of the rabbit elicited corneal opacification (0.9) and well defined conjunctival irritation (iris lesion 0; redness 1.1; chemosis 0.67). All reactions had resolved 3 or 7 days after instillation.

 

In a study (Cytec, 1984), which followed the method described in FIFRA (Federal Insecticide, Fungicide, and Rodenticide Act), the test item was tested for its eye irritant potential in rabbits. Therefore 0.1 mL undiluted test substance was instilled into the eyes of 6 white rabbits. After 24h the treated eye was rinsed. The test item produced moderate to severe but reversible ocular irritation. All six animals exhibited corneal opacity and ulceration and moderate to severe conjunctival irritation (redness, chemosis, discharge; some necrosis). Based on the results from the 24, 48 and 72 hour readings, the following mean values were calculated: cornea opacity 1.67, iris lesion 0.4, redness of conjunctiva 2.67 and edema 2.3. All eyes were free of significant irritation within 7 to 10 days after test material administration.

 

A further (pre)study (Cytec, 1992) was performed to assess the eye irritation potential of the test item to the rabbit. The method followed was that described in EEC Guideline B.5. Only one rabbit was administered a single ocular dose of 0.1 ml of the test substance and observed for three days after instillation. Severe ocular lesions were reported and diffuse crimson-red coloration of the conjunctivia with marked swelling and haemorrhaging of the nictating membrane was observed. Mean values were calculated to be: cornea opacity 2.0, iris lesion 1.0, redness of conjunctiva 2.0 and edema 3.0. The pilot rabbit was killed, on humane grounds, three days after instillation and no further animals were treated. Consequently, no data is available about reversibility of the finding. The severity of effects was comparable to other studies, so reversibility is considered likely.

 

Conclusion

Based on the available data, well-defined to moderate signs of irritation were observed on the treated eyes. Therefore, the substance is considered to be irritating to the eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available data on skin and eye irritation are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the available data, the substance is not considered to be classified for skin irritation but for eye irritation, Cat. 2, H319 under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.