Reaction mass of N-[3-(dimethylamino)propyl]stearamide and N-[3-(dimethylamino)propyl]hexadecan-1-amide

Endpoint summary

Description of key information

Skin and eye irritation of the test item has been evaluated in in vivo OECD 404 and 405 GLP studies.

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:

1981

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Description: white waxy soìid
Container: plastic screw-top container
Sponsor's identification: DMAPSA
Date of arrival: 24 July 1990
Storage conditions: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.42-2.62 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet and water (e.g. ad libitum): Free access to mains drinking water and food (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K. ) was allowed throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-27
- Humidity (%): 64-73
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5g

VEHICLE
- Amount(s) applied: 0.5mL of distilled water

Duration of treatment / exposure:

4h

Observation period:

1, 24, 48, 72h and 7d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal/ flank area
- Type of wrap if used: 2.5cm x 2.5 cm gauze patch
The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked i n distiIIed water.
- Time after start of exposure: 4h after application

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : 1, 24, 48, 72h and 7d

SCORING SYSTEM:
- Method of calculation: scale of Draize J.H. (1959)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 3d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 3d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 3d

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritant / corrosive response data:

Very sìight to well-defined erythema was noted at all treatment sites one to 48 hours after treatment. Well-defined erythema persisted at two treated skin sites at the 72-hour observation. L'ght brown scabbing at the remainìng treated skin site precluded evaluation of the skin responses at this time. At the 7-day observation no erythema was observed at the three treatment sites but incidents of hyperkerinisation and glossy skin were noted.
Very slight to slìght oedema was noted at two treated skin sites up to the 48 or 72-hour observations. Very slight to moderate oedema was noted at the remaining treatment site during the study but evaluation of oedema was not possible at the 72-hour observation time at this site due to other adverse dermal reactions.

Individual scores are provided below for skin irritation

	Observation time	Rabbit 1 (male)	Rabbit 2 (male)	Rabbit 3 (male)
Eythema formation	1h	1	2	2
	24h	2	2	2
	48h	2	2	2
	72h	2	2	? eSp
	7d	0 Hy	0 Hy	0 Gl
Oedema formation	1h	1	1	1
	24h	2	2	3
	48h	1	2	2
	72h	0	1	?0d
	7d	0	0	0

Hy = possible hyperkeratinisation

Sp = scab appears restricted to skin surface

Od = well-defined oedema

GL = glossy skin

?e = presence of adverse dermal reactions precludes macroscopic observation of erythema

Interpretation of results:

GHS criteria not met

Conclusions:

The test material DMAPSA, was classified as a moderate irritant to rabbit skin. No corrosive effects were noted.
The test material was also classified as 'irritant according to EEC Iabelìing regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are requìred.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals

(1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC. The results may be used as a basis for classification and labelling under Commission Directive 83/467/EEC and the U.K. Approved Code of Practice "Classification and Labelling of Substances Dangerous for Supply".

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema, well-defined to moderate oedema, hyperkeratinisation, hardened light brown scab and glossy skin. In one animal adverse dermal reactions precluded macroscopic observation of erythema and oedema at the 72 -hour observation.

The test material DMAPSA, was classified as a moderate irritant to rabbit skin. No corrosive effects were noted.

The test material was also classified as 'irritant according to EEC Iabelìing regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are requìred.

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

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

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Test material: DMAPSA (Octadecanamide, N-(3-(dimethylamino)propyl)-) (CAS No. 7651-02-7).
Date of receipt: 24th July 1990.
Description: White waxy solid.
Storage: In original container at room temperature.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.14 kg
- Housing: The animal was housed in a suspended metal cage
- Diet and water (e.g. ad libitum): Free access to mains drinking water and food (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.) was allowed throughout the study.
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 62-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL (corresponding to 64.3 mg)

Duration of treatment / exposure:

24h

Observation period (in vivo):

1 & 24h

Number of animals or in vitro replicates:

1

Details on study design:

SCORING SYSTEM: grades of Drajze J.H. (1959)
TOOL USED TO ASSESS SCORE: Examinat'ion of the eye was facilitated by use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

other: The animal showed signs of pain and discomfort 24-h after treatment and therefore was kiIIed in accordance with Home Office Guidelines

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

other: The animal showed signs of pain and discomfort 24-h after treatment and therefore was kiIIed in accordance with Home Office Guidelines

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Max. score:

3

Reversibility:

other: The animal showed signs of pain and discomfort 24-h after treatment and therefore was kiIIed in accordance with Home Office Guidelines

Remarks on result:

other: unable to score for redness due to white appearance of the conjunctival and nictitating menbranes.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: The animal showed signs of pain and discomfort 24-h after treatment and therefore was kiIIed in accordance with Home Office Guidelines

Irritant / corrosive response data:

Diffuse corneal opacity, iridial inflammation and severe conjunctìval irritation were observed within 24 hours following treatment. In addition sloughing of the conjunctival and nictitating membrane, haemorrhage of the conjunctivaì membrane, blood stained discharge and a white appearance of the nictitating and conjunctival membrane were observed.
Twenty-four hours after treatment the animal showed signs of pain and discomfort and therefore was kiIIed in accordance with Home Office Guidelines.

Individual scores are provided below for eye irritation

Time after treatment	1h	24h
Cornea
E = degree of opacity	d	3
F = area of oapacity	4	4
Score (ExF)x5	0	60
Iris
D	1	1
Score (Dx5)	5	5
Conjunctivae
A = Redness	2	? SLHW
B = Chemosis	3	4
C = Discharge	3	3 BL
Score (A+B+C)x2	16	14-20
Total score	21	79-85

 

D = dulling of the normal lustre of the corneal surface

BL = blood stained discharge

SL = sloughing of the conjunctival and nictitating membranes

H = haemorrhage of the conjunctival membrane

W = nictitating and conjunctival membranes white in appearance

? = unable to score for redness due to white appearance of the nictitating and conjunctival membranes

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test material, DMAPSA, was regarded as at least a severe irritant to the rabbit eye (based on one rabbit only).
The test material, DMAPSA, was also considered as a severe irritant to the rabbit eye according to EEC Iabelling regulations.
It is reasonable to assume the symbol "Xi" and highest risk phrase R 41 "RISK 0F SERI0US DAMAGE T0 EYES" are therefore required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand tlhite rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals

(1987) N0.405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 67/548/EEC. The results may be used as a basis for classification and labelling under Commission Directive 83/467/EEC and the U.K. Approved Code of Practice "Classification and Labelling of Substances Dangerous for Supply".

A single application of the test material to the non-irrigated eye of one rabbit produced diffuse corneal opacity, irridial inflammation and severe conjunctival irritation. In addition sloughing of the conjunctival and

nictitating membrane, haemorrhage of the conjunctival membrane, blood stained discharge and a white appearance of the nictitating and conjunctival membranes were observed.

The test material produced a maximum total score of 79 - 85 and was regarded as at least a severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit).

The test material, DMAPSA, was regarded as at least a severe irritant to the rabbit eye (based on one rabbit only).

The test material, DMAPSA, was also considered as a severe irritant to the rabbit eye according to EEC Iabelling regulations.

It is reasonable to assume the symbol "Xi" and highest risk phrase R 41 "RISK 0F SERI0US DAMAGE T0 EYES" are therefore required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

The test item is not classified for skin corrosion/irritation hazards based on CLP criteria.

The test item produces a positive response with corneal opacy of 4 in the only tested animal after 24h. The animal showed signs of pain and discomfort 24-h after treatment and therefore was kiIIed in accordance with Home Office Guidelines. Reversibility is theefore not demonstrated.

The test item is classified as Eye damage (H318) based on CLP criteria.