Tris[2-[[2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl]oxy]ethyl]amine

Eye irritation

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

Test material information

Constituent 1

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:

2-[(2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)oxy]-N,N-bis{2-[(2,4,8,10-tetra-tert-butyldibenzo[d,f][1,3,2]dioxaphosphepin-6-yl)oxy]ethyl}ethanamine

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

Results

Results 1

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

Results 2

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).