Propylidynetrimethyl trimethacrylate

Endpoint summary

Description of key information

No signs of skin irritation in a GLP study conducted according to OECD guideline 404 (null scores for erythema and edema in all animals) were observed. Only slight signs of eye irritation were observed in a GLP study conducted according to OECD guideline 405.
So, in conclusion, TMPTMA is considered to be not skin or eye irritating.

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:

From July 05 to 08, 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

Deviations:

yes

Remarks:

systemic effects not followed; animals not weighed at the end of the study

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) (BCM IPS Limited, London, UK), ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

Three males

Details on study design:

TEST SITE
- Area of exposure: Dorsal flank area
- Type of wrap if used: Test material (0.5 mL) was applied beneath a gauze (2.5 cm X 2.5 cm), placed directly on the test sites and then secured in position with surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24H

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Very slight erythema was observed at the application sites which subsided within 24 hours
- See table 1 for individual animal scores

Other effects:

No

Table 1: Individual skin reactions

Rabbits No.		62 Male	63 Male	64 Male
Erythema/Eschar	1 hour	1	1	1
	24 hours	0	0	0
	48 hours	0	0	0
	72 hours	0	0	0
Mean (24 hours + 48 hours + 72 hours)		0	0	0
Oedema	1 hour	0	0	0
	24 hours	0	0	0
	48 hours	0	0	0
	72 hours	0	0	0
Mean (24 hours + 48 hours + 72 hours)		0	0	0

Interpretation of results:

GHS criteria not met

Remarks:

not skin irritating

Conclusions:

Under the test conditions, TMPTMA is not classified as irritating to the skin according to the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a primary dermal irritation GLP study performed according to OECD guideline 404, three New-Zealand white male rabbits were dermally exposed to 0.5 mL of TMPTMA, under a semi-occlusive bandage (25 cm X 25 cm) for 4 hours to clipped skin of dorsal flank area. Animals then were observed for 72 hours. Irritation was scored by the method of Draize (1959).

 

Very slight erythema was observed at the application sites which subsided within 24 hours. Mean individual scores at 24, 48 and 72 hours after removal of the test material for the 3 animals were 0, 0, 0 for erythema/oedema score. In this study, TMPTMA is not a dermal irritant on male rabbits.

 

Under the test conditions, TMPTMA is not classified as irritating to the skin according to the criteria of the CLP Regulation (EC) N° 1272-2008.

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 July 11 to 21, 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no data on non-ocular local and systemic adverse effects

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): Certified Rabbit Diet (Code 5322) (BCM IPS Limited, London, UK), ad libitum
- Water (e.g. ad libitum): Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hour): 15/hour
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Three males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Not applicable

SCORING SYSTEM: Draize (1977) scoring system

TOOL USED TO ASSESS SCORE: Eye examinations were performed using light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

for each animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

for each animal

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

for each animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

- Minimal conjunctival irritation was noted in all treated eyes 1 and 24 hours after treatment and in one treated eye at the 48 hour observation; irritation completely resolved within 72 hours
- See table 1 and 2 for further details

Other effects:

No data

Table 1: Individual eye irritation scores

Animal	Time after dosing (hours)	Cornea		Iris	Conjunctivae
		Opacity	Area		Redness	Chemosis	Discharge
126 Male	1	0	0	0	1	0	1
	24	0	0	0	1	0	0
	48	0	0	0	1	0	0
	72	0	0	0	0	0	0
30 Male	1	0	0	0	1	1	1
	24	0	0	0	1	0	0
	48	0	0	0	0	0	0
	72	0	0	0	0	0	0
31 Male	1	0	0	0	1	1	1
	24	0	0	0	1	0	0
	48	0	0	0	0	0	0
	72	0	0	0	0	0	0

Table 2: Mean (24, 48 and 72 hours) value eye irritation scores

Animal	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
126 Male	0	0	0.7	0
30 Male	0	0	0.3	0
31 Male	0	0	0.3	0

Interpretation of results:

GHS criteria not met

Remarks:

not eye irritating

Conclusions:

Under the test conditions, TMPTMA is not classified as irritating to the eye according to the CLP Regulation (EC) N° (1272-2008).

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 undiluted TMPTMA in their right eye (under local anaesthesia) while the other eye corresponded to the control. The eyes were examined unwashed and the changes were observed at 1, 24, 48 and 72 hours after dosing and graded according to the method of Draize (1977).

 

Minimal conjunctival irritation was noted in all treated eyes 1 and 24 hours after treatment and in one treated eye at the 48 hour observation. The irritation completely resolved within 72 hours. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.3, 0.3 for conjunctivae score and 0, 0, 0 for chemosis score.

 

Under the test conditions, TMPTMA is not classified as irritating to the eye according to the CLP Regulation (EC) N° 1272-2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation
A recent GLP study (2005) conducted according to OECD guideline 404, using TMPTMA, showed that mean individual scores at 24, 48 and 72 h after removal of the test material for 3 rabbits were 0, 0, 0 for erythema/oedema score. This study was chosen as key study because it was the most recent study and because other studies had less details about test substance and animal housing conditions. Another study performed in similar conditions confirmed this result. A study conducted in drastic conditions (24 h exposure in occusive conditions) showed only slight signs of skin irritation.

In a primary dermal irritation GLP study (1996) performed according to OECD guideline 404, three New-Zealand white rabbits were dermally exposed to 0.5 mL of TMPTMA, under a semi-occlusive conditions for 4 hours to clipped skin of dorsal flank area. Animals were then observed for 72 hours. Irritation was scored by the method of Draize (1959). Very slight erythema was observed at the application sites which subsided within 24 hours. Mean individual scores at 24, 48 and 72 hours after removal of the test material for the 3 animals were 0, 0, 0 for erythema/oedema score. In this study, TMPTMA is not a dermal irritant in rabbits.

 

Eye irritation

A recent GLP study (2005) conducted according to OECD guideline 405, using TMPTMA, showed that mean individual scores at 24, 48 and 72 h after exposure of 3 rabbits were 0, 0, 0 for cornea score; 0, 0, 0 for iris score; 0.7, 0.3, 0.3 for conjunctivae score and 0, 0, 0 for chemosis score. This study was chosen as key study because it was the most recent study and because other studies and less details about test substance and animal housing conditions.

In another GLP eye irritation study (1999) conducted similarly to OECD guideline 405, no signs of irritation were observed in 6 rabbits.

Justification for classification or non-classification

In studies conducted according to OECD guidelines, no signs of eye and skin irritation that could lead to classification were observed. Therefore, TMPTMA is not classified according to the CLP Regulation (EC) N° (1272-2008).