N,N-Diethylacrylamide

Endpoint summary

Description of key information

Skin irritation:

A single occlusive application of test item to intact and abraded rabbit skin for 24 hours elicited well-defined to moderate dermal reactions and is classified as moderate irritant.

Eye irritation:

Instillation of test item into rabbit eye elicited severe ocular lesions. Due to the severity of the reaction no further animals were exposure to the test item.

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 1993-05-18 to 1993-05-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulation, Title 16, Section 1500.41

GLP compliance:

yes

Specific details on test material used for the study:

Batch No.: not specified
Purity: not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfied (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: approximately 13 to 14 weeks
- Weight at study initiation: 2.9 to 3.3 kg
- Housing: be housed individually in plastic cages with perforated floors
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30 to 70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hours period

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 100 mm x 100 mm
- Type of wrap if used: "Elastoplast " elastic adhesive dressing backed with "Sleek" waterproof strapping.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treament sites were washed with warm water (30 to 40 °C)

OBSERVATION TIME POINTS: on Day 2 (i.e. approximately 30 min after removal of dressings) and on Day 4 (equivalent to 24 and 72 hours after exposure).

SCORING SYSTEM: Draize
- Method of calculation: the numberical scores for erythema and oedema at both 24 and 72 hour readings for both intact and abraded skin sites were added together and divided by 24 to give the primary irritation index (PII)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.5

Max. score:

1

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.5

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Remarks on result:

other: abraded skin

Remarks:

only scored at 24 h and 72 h, not determined at 48h

Irritant / corrosive response data:

Very slight to well-defined erythema with or without very slight to slight oedema was seen at the intact and abraded sites of all six animals at the 24 hours reading. By the 72 hours reading very slight to moderate erythema and oedema was seen in all six animals. Harding of the skin was seen at the abraded site of two animals at the 72 hours reading. Very slight to well-defined erythema with or without very slight to slight oedema was seen at the intact and abraded sites of all six animals at the 24 hours reading. By the 72 hours reading very slight to moderate erythema and oedema was seen in all six animals. Harding of the skin was seen at the abraded site of two animals at the 72 hours reading.

Dermal reaction observed after application of test item

Rabbit number and sex	E=Erythema    O=Oedema	24 hours		72 hours
		intact	abraded	intact	abraded
1939 female	E	1	1	1	1
	O	0	0	1	1
1946 female	E	2	2	2	2
	O	2	2	2	2
1941 male	E	2	2	2	b3
	O	2	2	2	3
1942 male	E	2	2	2	b3
	O	1	2	2	3
1943 male	E	2	2	2	3
	O	1	2	2	2
1944 female	E	1	2	1	3
	O	0	2	1	2

Interpretation of results:

other: classified as a moderate irritant

Conclusions:

A single occlusive application of test item to intact and abraded rabbit skin for 24 hours elicited well-defined to moderate dermal reactions and is classified as moderate irritant.

Executive summary:

The study was performed to assess the skin irritation potential of the test item to the rabbit. The method followed in Code of Federal Regulations, Title 16, Section 1500.41.

 

Six rabbits were each administered a dermal dose of 0.5 ml of test substance to one intact and one abraded skin site and observed for three days.

 

A single occlusive application on test item to intact and abraded rabbit skin for 24 hours elicited well-defined to moderate dermal reactions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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 1993-05-24 to 1993-06-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

GLP compliance:

yes

Specific details on test material used for the study:

Batch No.: not specified
Purity: not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: England
- Age at study initiation: approximately 14 weeks age
- Weight at study initiation: 3334g
- Housing: be housed individually in a plastic cage with a perforated floor
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19
- Humidity (%): 30 to 70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hours period

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1

Details on study design:

The eye were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.

One animal was treated in advance of the others, to ensure that if severe response was produced. No further animals would be exposed.

A 0.1 mL amount of the test substance was placed into the everted lid of one eye.

The eyelids were then gently held together for one second before releasing. The contralateral eye reminded untreated.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

A corneal opacity developed one day after instillation. (Dulling and stripping of the epithelial cells were seen one hour after installation).

Iridial inflammation was observed one hour after instillation and 24 hours after installation has developed to Grade 2.

A beefy red colouration of the conjunctive accompanied by considerable swelling with partial eversion of the eyelids was observed. Blanching was observed in the nictating membrane.

Due to the severity of the reaction no further animals were exposure to the test item.

Ocular reations observed after instillation of the test item

rabbit number and sex	region of eye		1 hour	day after installation
				1	2	3	4	7	14	21
1849 male*	cornea		DA	1	1	1	1	1	1	0
	iris		1	2	1	1	1	0	0	0
	conjunctiva	redness	B2	B2	B2	B3	B3	B2	B2	0
		chemosis	2	2	2	2	2	1	1	0

* pilot animal

A stripping of the nictating

B blanching on the nictating membrane

D dulling of the normal lustre of the cornea

Conclusions:

Instillation of test item into rabbit eye elicited severe ocular lesions.
Due to the severity of the reaction no further animals were exposure to the test item.

Executive summary:

The study was performed to assess the eye irritation potential of the rabbit. The method followed was in EEC methods for the determination of toxicity, Directive 84/449/EEC, part B, Method B.5. Acute toxicity (eye irritation).

 

One rabbit was administered a single ocular dose of 0.1 mL of the test item and observed for 21 days after instillation.

 

A single instillation of the test item into eye of the rabbit elicited severe ocular lesions.

 

In view of the severity of the ocular reactions seen no further testing was performed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation/corrosion:

Mean scores at 24, 48 & 72 hours for erythema were >2.3 in at least 2 of 3 tested animals (actual value: mean scores at 24/72h for erythema were 2.5 in 4 of 6 tested animals).

Serious eye damage/eye irritation:

Mean scores at 24, 48 & 72 hours for corneal opacity were >1 (actual value 1), for iris were >1 (actual value 1.3), for conjunctival redness were >2 (actual value 2.3) and for chemosis were >2 (actual value 2).

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.2.2 & 3.3.2, this substance should be classified as Skin irritation category 2 and Eye irritation category 2.