1,3-Propanediol, 2,2-bis(hydroxymethyl)-, allyl ether

Endpoint summary

Description of key information

A skin irritation study in rabbits conducted according to OECD test guideline 404 is available. The maximum mean score for erythema was 0.67 and for oedema, the maximum mean score was 0.33 and therefore below the trigger for classification. Based on the results of this study, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether is not classified for eye irritation according to the CLP Regulation.

A eye irritation study in rabbits conducted according to OECD test guideline 405 is available. The calculated mean scores for redness, discharge, chemosis, iris and corneal lesions for all animals at 24, 48 and 72h after treatments were 0. Based on the results of this study, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether is not classified for eye irritation according to the CLP Regulation.

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:

04/05/1988 - 07/05/1988

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:

(1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Buckmasters, Henham, Hertfordshire, England
- Age at study initiation: approximately 8 to 13 weeks
- Weight at study initiation: 1.9 - 2.8 kg
- Housing: Individually housed in metal cages with perforated floors
- Diet: Ad libitum (SDS Standart Rabbit Diet)
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: approximately 19°C
- Humidity: 30 - 70%
- Air changes: 19 per hr
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

with an electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

3 male

Details on study design:

TEST SITE
- Area of exposure: dorso- lumbar region
- Coverage: approximately 10 cm square
- Type of wrap if used: Elastoplast elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, the treatment site was washed using water to remove any residual test substance
OBSERVATION TIME POINTS
Day 1 (approximately 30 minutes after removal of the patches and Days 2 (24hrs),3 (48hrs) and 4 (72 hrs)

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 (beef redness) to eschar formation preventing grading of erythema 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 approximately 1mm) 3
Severe oedema (raised more than 1mm and extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72hrs

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Very slight erythema accompanied by very slight oedema was observed in all three animals after removal of the dressings. All reactions had resolved by day 3 or 4 of the study

Other effects:

No adverse local or systemic effects were observed

Dermal reactions

Rabbit Number and Sex		Day
		1*	2	3	4
#1 Male	Erythema	1	1	1	0
	Oedema	1	1	0	0
#2 Male	Erythema	1	1	1	0
	Oedema	1	1	0	0
#3 Male	Erythema	1	1	0	0
	Oedema	1	1	0	0

* Approximately 30 minutes after removal of the dressing

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether produced very slight dermal irritation effects. However, the test material does not meet the requirement for classification as an irritant to the skin according to the Annex VI of the Regulation (EC) No 1272/2008 (CLP).

Executive summary:

The skin irritation potential of 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether was investigated in a rabbit study (OECD 404). 0.5mL of the test material was applied under semi-occlusive conditions for a 4 hour period to the shorn dorsal of three rabbits. Animals were observed on Day 1 (30 minutes after removal of the patches) and on Days 2, 3 and 4 for oedema and erythema and skin irritation was assessed. Very slight erythema accompanied by very slight oedema was observed in all three animals after removal of the dressings. All reactions had completely resolved Day 3 or 4 of the study. For each animal, the maximum mean score for erythema was 0.67 and for oedema, the maximum mean score was 0.33. 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether does not therefore meet the requirement for classification as a skin irritant according to the CLP Regulation.

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:

5 July 1993 - 9 July 1993

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:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Chesire, U.K.
- Age at study initiation: 12 - 16 weeks old
- Weight at study initiation: 2.44 - 2.58 kg
- Housing:Suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20- 23 °C
- Humidity: 59- 65 %
- Air changes: 15 per hr
- Photoperiod: 12 hrs dark /12 hrs light

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied : 0.1 mL

Duration of treatment / exposure:

Not applicable, the eyes were not rinsed after the instillation of the test item

Observation period (in vivo):

1, 24,48 and 72 hours after treatment

Number of animals or in vitro replicates:

3 animals

Details on study design:

- 0.1 mL of test substance was instilled in the right eye of test animals
- Washing: The eyes were not rinsed after application of the test material

SCORING SYSTEM:Draize scale, according to OECD TG 405

TOOL USED TO ASSESS SCORE: Light source from a standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Minimal conjunctival redness was noted in all treated eyes 1hr after treatment but all eyes appeared normal at the 24-hr observation.

Other effects:

Residual test material was noted around the treated eye of all animals 1 hr after treatment

Scores for irritation

Animal No. /Sex	Region of the eye		Hours (h) after treatment				Mean^a
			1h	24h	48h	72h
101/ F	Cornea	Opacity	0	0	0	0	0
		Area involved	0	0	0	0
	Iris		0	0	0	0	0
	Conjuctiva	Redness	1	0	0	0	0 0
		Chemosis	0	0	0	0
		Discharge	0^b	0	0	0
34/ M*	Cornea	Opacity	0	0	0	0	0
		Area involved	0	0	0	0
	Iris		0	0	0	0	0
	Conjuctiva	Redness	1	0	0	0	0 0
		Chemosis	0	0	0	0
		Discharge	0^b	0	0	0
97/ F*	Cornea	Opacity	0	0	0	0	0
		Area involved	0	0	0	0
	Iris		0	0	0	0	0
	Conjuctiva	Redness	1	0	0	0	0 0
		Chemosis	0	0	0	0
		Discharge	0^b	0	0	0

a Mean of 24, 48 and 72 hour readings

b Residual test material around treated eye

*One drop of ophthaine was instilled into each eye 1-2 minutes before dosing

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether induced no significant eye irritation to test animals. The test substance is not classified as irritating to the eyes according to the criteria of the Annex VI of the Regulation (EC) No 1272/2008 (CLP)

Executive summary:

In an eye irritation study performed according to OECD guideline 405 and in compliance with GLP, 0.1 mL of undiluted test material 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether was instilled into the right eye of three New Zealand White Rabbits. The eyes were not rinsed after the instillation of the test item. The left eye remained untreated and served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. No corneal or iridial effects were noted during the study. Residual test material was noted around the treated eye of all animals 1 hour after treatment. Additionally, minimal conjunctival redness was noted in all treated eyes 1 hour after treatment but all eyes appeared normal at the 24-hour observation. The calculated mean scores for redness, discharge, chemosis, iris and corneal lesions for all animals at 24, 48 and 72h after treatments were 0. Based on the results of this study, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether is not classified for eye irritation according to the CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential of 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether was investigated in a rabbit study (OECD 404). 0.5 mL of the test material was applied under semi-occlusive conditions for a 4 hour period to the shorn dorsal of three rabbits. Animals were observed on Day 1 (30 minutes after removal of the patches) and on Days 2, 3 and 4 for oedema and erythema and skin irritation was assessed. Very slight erythema accompanied by very slight oedema was observed in all three animals after removal of the dressings. All reactions had completely resolved Day 3 or 4 of the study. For each animal, the maximum mean score for erythema was 0.67 and for oedema, the maximum mean score was 0.33. 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether does not therefore meet the requirement for classification as a skin irritant according to the CLP Regulation.

Eye irritation

The eye irritation potential of 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether was investigated in a rabbit study (OECD 405).0.1 mL of the undiluted test material was instilled into the right eye of three New Zealand White Rabbits.  Animals were observed at 1, 24, 48 and 72 hours after dosing. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. No corneal or iridial effects were noted during the study. Residual test material was noted around the treated eye of all animals 1 hour after treatment. Additionally, minimal conjunctival redness was noted in all treated eyes 1 hour after treatment but all eyes appeared normal at the 24-hour observation. The calculated mean scores for redness, discharge, chemosis, iris and corneal lesions for all animals at 24, 48 and 72h after treatments were 0. Based on the results of this study, 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether is not classified for eye irritation according to the CLP Regulation.

Justification for classification or non-classification

Based on the results of the skin abd eye irritation studies, the submission substance 1,3-propanediol, 2,2- bis(hydroxymethyl) -, allyl ether does not require classification for skin or eye irritation according to the CLP Regulation.