Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Molecular formula:
Not relevant
IUPAC Name:
Reaction mass of N-[3-(Dimethylamino)propyl]stearamide and N-[3-(Dimethylamino)propyl]hexadecan-1-amide
Test material form:
solid
Details on test material:
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.
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.

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.