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:
Aug - Sep 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material in an amount of 0.1 g was inserted into the conjunctival sac of the left eye of the rabbits and the lids were gently closed for a few seconds. The right eye was not treated and served as an untreated control. In 3 of the 9 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline. The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7 and was scored for each individual rabbit.
GLP compliance:
no
Remarks:
pre-GLP study

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine
EC Number:
279-459-6
EC Name:
Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine
Cas Number:
80410-33-9
Molecular formula:
C90H132NO9P3
IUPAC Name:
tris[2-({4,6,12,14-tetra-tert-butyl-8,10-dioxa-9-phosphatricyclo[9.4.0.0^{2,7}]pentadeca-1(11),2(7),3,5,12,14-hexaen-9-yl}oxy)ethyl]amine
Test material form:
solid

Test animals / tissue source

Species:
rat
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited
- Weight at study initiation: 2 -3 kg
- Housing: individually
- Diet: standard rabbit food (NAFAG, No. 814, Gossau SG); ad libitum
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 12 / 12


Only rabbits with normal ophthalmic findings were used for these tests.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
- removal of test substance: approx. 30 sec
- no removal of test substance: until end of observation period
Observation period (in vivo):
until 7 days after application of the test substance
Number of animals or in vitro replicates:
3 males and 6 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 9 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of physiological saline.

SCORING SYSTEM:
CORNEA:
A Opacity and degree of density (most dense area scored)
No opacity - 0
Scattered or diffuse area, details of iris clearly visible - 1
Easily discernible translucent areas, details of iris slightly obscured - 2
Opalescent areas, no details of iris visible, size of pupil barely discernible - 3
Opaque, iris invisible - 4

B Area of cornea involved
One quarter (or less) but not zero - 1
Greater than one quarter, but less than half - 2
Greater than half, but less than three quarters - 3
Greater than three quarters, up to whole area - 4

A X B X 5 Maximum possible score = 80

IRIS:
A Values
Normal - 0
Folds above normal, congestion, swelling, circumcornea injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) - 1
No reaction to light, hemorrhage, gross destruction (any or all of these) - 2

A X 5 Maximum possible score = 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctiva excluding cornea and iris)
Vessels normal - 0
Vessels definitely injected above normal - 1
More diffuse, deeper crimson red, individual vessels not easily discernible - 2
Diffuse beefy red - 3

B Chemosis
No swelling - 0
Any swelling above normal (includes nictitating membrane) - 1
Obvious swelling with partial eversion of lids - 2
Swelling with lids about half closed - 3
Swelling with lids about half closed to completely closed - 4

C Discharge
No discharge - 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) - 1
Discharge with moistening of the lids and hairs just adjacent to lids - 2
Discharge with moistening of the lids and hairs, and considerable area around the eye - 3

(A -K B + C) X 2 Maximum possible score = 20

Calculation of the primary eye irritation index:
The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4 and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.

Index 0 = none
0.1 - 10.9 = minimal
11.0 - 25.9 = slight
26.0 - 55.9 = moderate
56.0 - 84.0 = marked
above 84.0 = extreme

TOOL USED TO ASSESS SCORE: slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
other: mean of 1/2/3/4 and 7 days after exposure
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Remarks:
rinsed eye
Basis:
mean
Time point:
other: mean of 1/2/3/4 and 7 days after exposure
Score:
0.1
Reversibility:
fully reversible within: 2 days after exposure
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
primary irritation index in unrinsed eyes = 0
primary irritation index in rinsed eyes = 0.1

Any other information on results incl. tables

No symptoms of intoxication were observed throughout the test period.

Table 1: Calculation of the primary irritation index

Time after exposure days

mean reaction score

 

 

unrinsed eyes (A)

rinsed eyes (B)

cornea

iris

conjunctiva

cornea

iris

conjunctiva

 

1

 

0

 

0

 

0

 

0

 

0

 

0.7

2

0

0

0

0

0

0

3

0

0

0

0

0

0

4

0

0

0

0

0

0

7

0

0

0

0

0

0

subtotal

0

0

0

0

0

0.7

total

 

0

0.7

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Executive summary:

Under the conditions of this experiment the test material was found to cause no irritation when applied to the rabbit eye mucosa (primary irritation index: 0) and a minimal irritation when the application site was rinsed (primary irritation index: 0.1).