Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-09-12 To 1978-10-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
Pre-GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): P0434 (dodecyl dimethyl amine oxide)
- Molecular formula (if other than submission substance): Not available
- Molecular weight (if other than submission substance): 235.7
- Substance type: Pure active substance
- Physical state: Liquid
- Analytical purity: Not available
- Impurities (identity and concentrations): None
- Composition of test material, percentage of components: See below
- Isomers composition: Not available
- Purity test date: Not available
- Lot/batch No.: Not available
- Expiration date of the lot/batch: Not available
- Stability under test conditions: Not available
- Storage condition of test material: Room temperature
- Other: None

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kings Wheel
- Age at study initiation: Young adult
- Weight at study initiation: Males: 1608.6 gm, Females: 2031.5 gm
- Housing:Individually in stainless steel cages with stainless steel slatted flooring
- Diet (e.g. ad libitum): Purins Lab Rabbit Chow (By Ralston Purina Company)
- Water (e.g. ad libitum): Tap water, from bottles with tubules made of refined steel, ad libitum
- Acclimation period: minimum 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 46-72
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): 12/12 (Fluorescent lighting)


IN-LIFE DATES: From: 1978-09-12 To: 1978-10-18

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml P0434
- Concentration (if solution): Undiluted


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
Group I: Eyes of animals were not rinsed, and observations are noted directly.
Group II: Eyes of animals were rinsed after 4 seconds by spraying 20 ml of lukewarm tap water after application.
Observation period (in vivo):
At 1 hour, 1,2,3,4,7,14,21,28 and 35 days.
Number of animals or in vitro replicates:
3 animals of either sex per group.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes of Group II animals were rinsed by spraying 20 ml of lukewarm tap water from a hypodermic syringe fitted with a snubbed 18 gauge needle into the eye under moderate pressure.
- Time after start of exposure: 4 seconds after application.


SCORING SYSTEM: Draize scoring system


TOOL USED TO ASSESS SCORE: A Pen light

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
till day 35. Vascularization was observed from day 21 onwards till the end of study (day 35)
Remarks on result:
other: No rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: No rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: No rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: No rinse
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
till day 35. Vascularization was observed from day 21 onwards till the end of study (day 35)
Remarks on result:
other: No rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: No rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: No rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: No rinse
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
till day 35. Vascularization was observed from day 21 onwards till the end of study (day 35)
Remarks on result:
other: No rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: No rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: No rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Cornea was normal throughout the study
Remarks on result:
other: Rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: Rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: Rinse
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: Rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: Rinse
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
till day 35. Vascularization was observed from day 21 onwards till the end of study (day 35)
Remarks on result:
other: Rinse
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iris was normal throughout the study.
Remarks on result:
other: Rinse
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
20
Reversibility:
fully reversible within: 14 days
Remarks:
Vascularization was observed from day 21 onwards till the end of study (day 35)
Remarks on result:
other: Rinse
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: Rinse
Other effects:
None

Any other information on results incl. tables

Table 1: The eye irritation response of animals (Group I - No rinse) exposed to undiluted P0434 (27.8% DDAO) (study# 21599)

Animal number Observation time Cornea Cornea Score Iris Iris Score Conjunctivae Conjunctivae Score
A (Degree of density) B (Area of cornea involved) AxBx5 A Ax5 A (Redness) B (Chemosis) C (Discharge) A+B+Cx2
Animal #1 1 hour 0 0 0 0 0 1 2 3 12
Day 1 1 4 20 0 0 1 2 3 12
Day 2 1 4 20 0 0 1 2 2 10
Day 3 1 4 20 0 0 1 2 2 10
Day 4 1 4 20 0 0 1 2 1 8
Day 7 1 4 20 0 0 1 1 1 6
Day 14 1 4 20 0 0 0 0 0 0
Day 21* 1 4 20 0 0 0 0 0 0
Day 28* 2 4 40 0 0 0 0 0 0
Day 35* 2 4 40 0 0 0 0 0 0
                     
Animal #2 1 hour 0 0 0 0 0 1 2 3 12
Day 1 1 4 20 0 0 1 2 2 12
Day 2 1 4 20 0 0 1 1 1 6
Day 3 1 4 20 0 0 1 1 1 6
Day 4 1 4 20 0 0 1 0 0 2
Day 7 1 4 20 0 0 1 0 0 2
Day 14 1 4 20 0 0 0 0 0 0
Day 21* 1 4 20 0 0 0 0 0 0
Day 28* 2 2 20 0 0 0 0 0 0
Day 35* 2 2 20 0 0 0 0 0 0
                     
Animal #3 1 hour 0 0 0 0 0 1 1 2 8
Day 1 1 4 20 0 0 1 2 1 8
Day 2 1 4 20 0 0 1 1 1 6
Day 3 1 4 20 0 0 1 1 1 6
Day 4 1 4 20 0 0 1 1 1 6
Day 7 1 4 20 0 0 1 1 1 6
Day 14 1 4 20 0 0 0 0 0 0
Day 21* 1 4 20 0 0 0 0 0 0
Day 28* 1 4 20 0 0 0 0 0 0
Day 35* 1 4 20 0 0 0 0 0 0

* Vascularization was observed. Vascularization refers to the invasion of the cornea by blood vessels.

Table 2: The eye irritation response of animals (Group II- Rinse) exposed toundiluted P0434 (27.8% DDAO) (study# 21599)

Animal number Observation time Cornea Cornea Score Iris Iris Score Conjunctivae Conjunctivae Score
A (Degree of density) B (Area of cornea involved) AxBx5 A Ax5 A (Redness) B (Chemosis) C (Discharge) A+B+Cx2
Animal #4 1 hour 0 0 0 0 0 1 2 3 12
Day 1 0 0 0 0 0 1 2 1 8
Day 2 0 0 0 0 0 1 0 1 4
Day 3 0 0 0 0 0 1 0 1 4
Day 4 0 0 0 0 0 1 0 0 2
Day 7 0 0 0 0 0 1 0 0 2
Day 14 0 0 0 0 0 0 0 0 0
                     
Animal #5 1 hour 0 0 0 0 0 1 2 2 10
Day 1 1 1 5 0 0 1 2 1 8
Day 2 1 1 5 0 0 1 0 1 4
Day 3 1 1 5 0 0 1 0 1 4
Day 4 1 1 5 0 0 1 0 0 2
Day 7 0 0 0 0 0 1 0 0 2
Day 14 0 0 0 0 0 0 0 0 0
                     
Animal #6 1 hour 0 0 0 0 0 1 2 3 12
Day 1 1 2 10 0 0 1 2 1 8
Day 2 1 2 10 0 0 1 0 1 4
Day 3 1 2 10 0 0 1 0 2 6
Day 4 1 2 10 0 0 1 0 2 6
Day 7 1 3 15 0 0 1 0 2 6
Day 14 1 2 10 0 0 0 0 0 0
Day 21* 1 2 10 0 0 0 0 1 2
Day 28* 1 2 10 0 0 0 0 1 2
Day 35* 1 2 10 0 0 0 0 0 0

* Vascularization was observed. Vascularization refers to the invasion of the cornea by blood vessels.

Overall irritation/ Corrosion results: For Rinse Group

Irritation parameter  Basis  Time point    Max.score  Reversibility  Remarks 
Overall irritation score  mean 1 hour   3.0 3.0  not fully reversible within:35 days  Rinse 
Cornea score  mean: all animals with grade 0  1 hour  not fully reversible within:35 days  Rinse 
Iris score    1 hour, 1,2,3,4,7,14,21,28 and 35 days  No iridal response was observed.  Rinse 
Conjunctival redness score  mean: all animals with grade 1 1 hour, 1,2,3,4 and 7 days  fully reversible within:14 days  Rinse 
Conjunctival chemosis score  mean  1 hour and day 1  fully reversible within: day 2  Rinse 
Overall irritation score  mean  day 1  3.67  3.67  not fully reversible within:35 days  Rinse 
Cornea score  mean: Two animals with grade 1 and one with grade 0 day 1,2,3,4  >0 -<1  not fully reversible within:35 days  Rinse 
Overall irritation score  mean  days 2,3,4  1.67  1.67  not fully reversible within:35 days  Rinse 
Conjunctival chemosis score  mean: all animals with grade 0  days 2,3,4,7,14,21,28 and 35 days   0 fully reversible within:2 days  Rinse 
Overall irritation score mean  day 7  1.33  1.33  not fully reversible within:35 days  Rinse 
Cornea score mean:one animal with grade 1 and two eith grade 0  day 7, 14  >0 - <1   not fully reversible within:35 days Rinse 
Conjunctival redness score  mean:all animals with grade 0  day 14,21,28 and 35  0  0  fully reversible within:14 days Rinse 
Overall irritation score  mean  day 14, 21,28 and 35  0.33   0.33  not fully reversible within:35 days Rinse 
Cornea score  mean:one animals with grade 1 and two with grade 0  day 14, 21, 28 and 35  >0 - <1   1 not fully reversible within:35 days  Rinse 

GHS Classification:

Animal #  GHS Classification  What it means? Cornea  Iris  Conjunctival redness Conjunctival chemosis  Days to clear by individual animal 
 No rinse (Group I)              
 1 Irreversible eye irritation  1.0   1.0 2.0  Cornea not reversible by 35 days 
 2 Irreversible eye irritation  1.0  0  1.0 1.33  Cornea not reveersible by 35 days 
Irreversible eye irritation  1.0   1.0 1.33 Cornea not reversible by 35 days 
Rinse (Group II)               
 1  1 Irreversible eye irritation  0.0   0  1.0  0.67 Fully reversible within 14 days 
 2  1 Irreversible eye irritation   1.0  0 1.0   0.67 Fully reveersible within 14 days 
 3  1 Irreversible eye irritation   1.0  0  1.0 0.67  Cornea not fully reversible by 35 days 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
P0434 (27.8% Dodecyl dimethyl amine oxide) causes irreversible irritation to the rabbit eye.
Executive summary:

The eyes of two groups of 3 rabbits were instilled with 0.1 ml of undiluted P0434 (27.8% DDAO). The eyes of the first group of 3 rabbits were not rinsed and the eyes of the second group of 3 rabbits were rinsed, approximately 4 seconds following instillation of the test material, with 20 ml of lukewarm distilled water.

Group I: The maximum average score was 4.0 at 1day. The observable response included irreversible corneal opacity in all three animals till 35 days, no iridic response was observed, conjunctival redness with grade 1 was observed which was fully reversed within 14 days and conjunctival chemosis upto grade 2 was observed which was fully reversed within 14 days.

Group II: The maximum average score was 3.67 at one day. The observable response included irreversible corneal opacity in one animal till 35 days, no iridic response was observed,conjunctival redness with grade 1 was observed which was fully reversed within 14 days and conjunctival chemosis up to grade 2 was observed which was fully reversed within 2 days.

From these observations it can be concluded that the test material P0434 (27.8% dodecyl dimethyl amine oxide) is causing irreversible irritation to the rabbit eye. Thus 27.8% DDAO can be classified as GHS category 1.