Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with diethylamine

Endpoint summary

Description of key information

Two reliable studies are available to evaluate the irritant potential of Diethylamine modified ethoxylated trimethylolpropane triacrylate.
Diethylamine modified ethoxylated trimethylolpropane triacrylate is slightly irritant for skin (Shakleton 1982) and irritant for eyes (Van Huygevoort 2002).
No data is available on irritation potential on respiratory tract.

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:

August-September 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The objective was 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 used is that described in the US Federal Register 1973, Vol.38, No.187, Section 1500:41.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS = Healthy females
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: in grid bottomed galvanised metal cages.
- Diet (e.g. ad libitum): 90-95g of a commercially available pelleted rabbit diet were provided for each animal at a similar time each day.
- Water (e.g. ad libitum): An automatic watering system provided a constant summply of drinking water to the cages.
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no details, but air-conditionned-room
- Photoperiod (hrs dark / hrs light): 10h/14h

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

No preparation of the supplied material was necessary.
0.5 ml of the test material was applied to each of two 2.5 cm square surgical lint pads attached to "sleek" plastic adhesive wrapping. The lint suares were then placed in contact with the animal's skin, one lint square in contact with abraded skin and one lint square with intact skin, bilateral to the midline, and secure in position by the attached "Sleek" adhesive tape. The entire trunk of the animal was then encircled with a length of elastic adhesive bandage 7.5 cm wide.

Duration of treatment / exposure:

24h

Observation period:

The reaction sites were assessed at 1 hour and at 48 hours after patch removal.

Number of animals:

6

Details on study design:

At least one hour before dosing the rabbits were placed in restraining stocks and the dorsal surface of the rabbits closely clipped ove an area consisting of approximately 10% of the total surface area, using an Oster model A.2 clipper with Angra blade.
The left flank was then lightly abraded with the point of 25 x 0.6 mm sterila disposable hypodermic needle. The abrasions were sufficiently deep to damage the stratum corneum but not to penetrate the dermis. the skin of the right flank remainded intact.

After a contact period of 24 hours the adhesive tapes and lint patches were removed from the animals. One hour was then allowed to permit irritation from the adhesive tapes to subsade then the reaction sites were assessed using the scoring system of Draize.

The values obtained for erythema at both abraded and intact sites at the 24 and 72 hour readings were summed and the total divided by six, the number of rabbits, to give an average score for erythema. The values obtained for oedema were treated in a similar manner to give an average score for aedema. A primary irritation score was calculated by adding the total value obtained for erythema to tje total of value obsained for oedema dividing by six to give an average of the total score. This average was then divided by four to give a value referred to as the primary irritation score.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

1.08

Max. score:

4

Reversibility:

no data

Remarks on result:

other: Intact skin / Individual scores = 2 - 1 - 0.5 - 0.5 - 0.5 - 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

no data

Remarks on result:

other: Intact skin / individual scores = 1 - 0 - 0 - 0 - 0 - 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

no data

Remarks on result:

other: Abraded skin / Individual scores = 2 - 1 - 1 - 0.5 - 1.5 - 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

6 rabbits

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

no data

Remarks on result:

other: Abraded skin / Individual scores = 1 - 0.5 - 0 - 0 - 0.5 - 2

Irritant / corrosive response data:

The average scores produced by the group of 6 rabbits were 4.8 for erythema and 2.3 for oedema, giving a primary irritation score of 1.8.
No data on reversibility of effects are showed.

Other effects:

no data

Interpretation of results:

GHS criteria not met

Remarks:

not skin irritating

Conclusions:

According to this study, Diethylamine modified ethoxylated trimethylolpropane triacrylate is considered as slightly irritant but it is not classified as skin irritant according to CLP criteria.

Executive summary:

The objective of this study was to investigate the degree of irritation produced to the abraded and intact skin of 6 albino rabbits following 24 hours occluded contact with Diethylamine modified ethoxylated trimethylolpropane triacrylate.

Erythema and/or oedema were observed in all animals exposed to the substance (intact and abraded skin). However the effect are not severe, each score is equal or smaller than 2 (out of 4).

Diethylamine modified ethoxylated trimethylolpropane triacrylate is considered as slightly irritant but it is not classified as irritant according to CLP criteria.

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:

From December 24, 2001 to January 28, 2002

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:

1987

Deviations:

yes

Remarks:

animals not weighed at the end of the study

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 7-11 weeks
- Weight at study initiation: 1.45-2.03 kg
- Housing: Housed individually in labelled cages with perforated floors
- Diet: Standard laboratory rabbit diet (Charles River breeding and maintenance diet for rabbits, Altromin, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: Approximately 21 ± 3 °C
- Humidity: 30-70 %
- Air changes: Approximately 15 air changes/h
- Photoperiod: 12 h dark / 12 h artificial fluorescent light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: After 24 h observation, 2 % fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.

SCORING SYSTEM: Draize (1977) scoring system

TOOL USED TO ASSESS SCORE: Eye examination was performed using an ophthalmic examination lamp.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- Corneal injury was seen as opacity (maximum grade 1) and epithelial damage (maximum 75% of the corneal area) leads to development of pannus (neovascularisation of the cornea) in one animal 7 days after instillation.
- Corneal injury had resolved within 7 days in two animals and within 14 days in the other animal.
- Iridial irritation (grade 1) was observed in all animals and had resolved within 72 h.
- Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 7 days in one animal and within 14 days in the other two animals.
- Reduced elasticity of the eyelids was noted in one animal 72 h after instillation.
- Remnants of the test substance were present on the outside of the eyelids of one animal on Days 1, 2 and 3.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Table 1: Ocular reactions

Rabbit Number, sex & body weight	Region of eye		Time after treatment
			1 h	24 h	48 h	72 h	7 days	14 days
22 (male & 2031 g) Sentinel	Cornea	Opacity	1	1	1	1	0	0
		Area	3	2	3	1	0	0
		Fluor area (%)		50		25	0
	Iris		0	1	1	0	0	0
	Conjunctivae	Redness	2	2	3	3	1	0
		Chemosis	4	3	2	2	0	0
		Discharge	3	2	1	1	0	0
	Comments		c	c	c	f	-	-
107 (male & 1451 g)	Cornea	Opacity	1	1	1	1	0	0
		Area	2	3	3	2	0	0
		Fluor area (%)		75		35	0
	Iris		0	1	1	0	0	0
	Conjunctivae	Redness	2	3	3	2	0	0
		Chemosis	3	3	2	1	0	0
		Discharge	2	2	1	1	0	0
	Comments		-	-	-	-	-	-
109 (male & 1529 g)	Cornea	Opacity	1	1	1	1	0	0
		Area	1	3	3	2	0	0
		Fluor area (%)		75		35	0
	Iris		0	1	1	0	0	0
	Conjunctivae	Redness	2	3	3	2	1	0
		Chemosis	4	3	2	1	0	0
		Discharge	2	2	2	1	0	0
	Comments		-	-	-	-	p	-

 

Fluor area (%): green staining (percentage of total corneal area) after fluorescein treatment.

 

c - Remnants of the test substance on the outside of the eyelids.

f - Reduced elasticity of the eyelids.

p - Pannus (neovascularisation of the cornea)

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions, Diethylamine modified ethoxylated trimethylolpropane triacrylate is irritating to the eyes.

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of Diethylamine modified ethoxylated trimethylolpropane triacrylate in one eye, while the contralateral eye remained untreated and served as control. The study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 21 days later, after considering the degree of eye irritation observed in the first animal. The eyelids were then gently held together for about one second to prevent loss of the test material, and then released. The eyes were examined 1 and 24 h after instillation. After 24 h observation, 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. The eyes were also examined 48 and 72 h, 7 and 14 days after the treatment. Draize (1977) scoring system was followed to grade the ocular reactions. 

 

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Corneal injury was seen as opacity (maximum grade 1) and epithelial damage (maximum 75% of the corneal area) leads to development of pannus (neovascularisation of the cornea) in one animal 7 days after instillation. Corneal injury had resolved within 7 days in two animals and within 14 days in the other animal. Iridial irritation (grade 1) was observed in all animals and had resolved within 72 h. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 7 days in one animal and within 14 days in the other two animals. Reduced elasticity of the eyelids was noted in one animal 72 h after instillation. Remnants of the test substance were present on the outside of the eyelids of one animal on Days 1, 2 and 3. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 1, 1 for cornea score; 0.7, 0.7, 0.7 for iris score; 2.7, 2.7, 2.7 for conjunctivae score and 2.3, 2, 2 for chemosis score. In this study, Diethylamine modified ethoxylated trimethylolpropane triacrylate (ACTILANE 715) is an eye irritant on male rabbits.

  

Under the test conditions, Diethylamine modified ethoxylated trimethylolpropane triacrylate is Irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation (Haynes 1982)

The objective of this study was to investigate the degree of irritation produced to the abraded and intact skin of 6 albino rabbits following 24 hours occluded contact with Diethylamine modified ethoxylated trimethylolpropane triacrylate.

Erythema and/or oedema were observed in all animals exposed to the substance (intact and abraded skin). However the effect are not severe, each score is equal or smaller than 2 (out of 4).

Diethylamine modified ethoxylated trimethylolpropane triacrylate is considered as slightly irritant but it is not classified as skin irritant according to CLP criteria.

 

Eye irritation (Van Huygevoort 2002)

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 3 healthy male rabbits of the New Zealand White strain were exposed to 0.1 mL of Diethylamine modified ethoxylated trimethylolpropane triacrylate in one eye, while the contralateral eye remained untreated and served as control.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Corneal injury was seen as opacity (maximum grade 1) and epithelial damage (maximum 75% of the corneal area) leads to development of pannus (neovascularisation of the cornea) in one animal 7 days after instillation. Corneal injury had resolved within 7 days in two animals and within 14 days in the other animal. Iridial irritation (grade 1) was observed in all animals and had resolved within 72 h. Irritation of the conjunctivae was seen as redness, chemosis and discharge, which had completely resolved within 7 days in one animal and within 14 days in the other two animals. Reduced elasticity of the eyelids was noted in one animal 72 h after instillation. Remnants of the test substance were present on the outside of the eyelids of one animal on Days 1, 2 and 3. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 1, 1, 1 for cornea score; 0.7, 0.7, 0.7 for iris score; 2.7, 2.7, 2.7 for conjunctivae score and 2.3, 2, 2 for chemosis score.

In this study, Diethylamine modified ethoxylated trimethylolpropane triacrylate is an eye irritant on male rabbits.

  

Justification for classification or non-classification

Based on the available data, no classification for skin irritation of the registered substance is required according to the Regulation EC N°1272/2008.

Based on the available data, the registered substance should be classified as eye irritating (Eye irrit.2, H319) according to the Regulation EC N°1272/2008.