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Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Remarks:
Originally, the test was carried out for the purpose of another regulation- registration in the US according to TSCA - US EPA OPPTS 870.240 Acute Eye irritation [EPA712-C-98-195]
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 3 - January 6, 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Originally, the tst was carried out for the purpose of another rgulation- Registration in the US according to TSCA US EPA OPPTS 870.2400 Acute eye irritation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF 12- NOUSAN-8147
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 1-hydroxypropan-2-yl diethylphosphinate and 2-hydroxypropyl diethylphosphinate
Cas Number:
2230512-72-6
Molecular formula:
C7H17O3P
IUPAC Name:
Reaction mass of 1-hydroxypropan-2-yl diethylphosphinate and 2-hydroxypropyl diethylphosphinate
Test material form:
liquid
Details on test material:
R&D level

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Housing: The animals were singly housed in suspended stainless steel caging which
conforms to the size recommendations in the most recent Guide for the Care and Use
of Laboratory Animals (Natl. Res. Council, 20 11). Enrichment (e.g., toy) was placed
in each cage. Litter paper was placed beneath the cage and was changed at least three
times per week.
Animal Room Temperature and Relative Humidity Ranges: 20-23"C and 42-47%,
respectively.
Animal Room Air Changes/Hour: 13. Airflow measurements are evaluated regularly
and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 6 days
Food: Envigo Teklad Global High Fiber Rabbit Diet® #2031. A designated amount
of the diet (approximately ISO grams/day) and a Premium Timothy Cube™ (Ontario
Dehy Inc.) were available to each rabbit.
Water: Filtered tap water was supplied ad libitum.
Contaminants: There were no known contaminants reasonably expected to be found
in the food or water at levels which would have interfered with the results of this
study. Analyses of the food and water are conducted regularly and the records are
kept on file at Product Safety Labs

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml of test substance
Duration of treatment / exposure:
up to 72 hours post instilation
Observation period (in vivo):
1, 24, 48, 72 hours (Draize method)
Number of animals or in vitro replicates:
3
Details on study design:
PROCEDURE
A. Preparation and Selection of Animals
Prior to test initiation, both eyes of a group of animals were examined using a white I ight source
and a fluorescein dye procedure. One drop of ophthalmic fluorescein sodium dye was instilled
into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) after
instillation of the fluoresccin and then evaluated for corneal damage using an ultraviolet light
Source. Prior to test substance instillation, the eyes were re-examined and scored for
abnonnalities according to the "Scale for Scoring Ocular Lesions" (Draize et aI., 1944; see Table
4). Three healthy, naive animals (not previously tested) without pre-existing ocular irritation
were selected for test.
A systemic analgesic (Buprenorphine SR®) was administered to relieve potential discomfort
associated with eye irritation which provides therapeutic relief for periods of up to 76 hours.
Prior to test substance instillation, 0.1 mg/kg of body weight of the analgesic was administered to
the animals and at appropriate intervals to maintain therapeutic blood levels.
B. Preparation of Test Substance
The test substance was instilled as received and mixed well prior to use.
The pH was determined for the test substance prior to the instillation and was within a pH range
of 2 and 11.5, therefore testing proceeded. The procedure used and the results are retained in the
raw data.
C. Instillation
Prior to instillation, 1-2 drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic
Solution USP, 0.5%) were placed into both the treated and control eye of each animal. One-tenth
of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of
each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then
gently held together for about one second before releasing to minimize loss of the test substance.
The other eye of each rabbit remained untreated with the test substance and served as a control.
The rabbits were then returned to their designated cages.
D. Ocular Scoring
Ocular irritation was evaluated using a white light source in accordance with the Draize method
of scoring (Draize et aI., 1944; see Table 4) at I, 24, 48, and 72 hours post-instillation. The
fluorescein dye evaluation procedure described in Section 5.A. was used in the treated eye at 24
hours to verity the absence of corneal damage. Individual scores were recorded for each animal.
In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were
noted. The average score for all rabbits at each scoring period was calculated to aid in data
interpretation.
E. Classification of Eye Scores
The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all
rabbits was used to classity the test substance by the system of Kay and Calandra (Kay &
Calandra, 1962).
F. Cage-Side Observations
The animals were observed for signs of gross toxicity and behavioral changes at least once daily
during the test period.
G. Body Weights
Individual weights of animals were recorded shortly before instillation of the test substance
(initial) and at the completion of testing (tenninal). Additional body weights were taken to
determine the appropriate amount of analgesic. These additional body weights were recorded in
the raw data but are not reported.
H. Study Termination
Once testing was complete, the animals were released for euthanasia and humanely euthanized.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
48 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
48 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
>= 0
Max. score:
80
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
48 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
48 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
72 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
>= 0
Max. score:
10
Reversibility:
other:
Remarks:
no indication of irritation
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
>= 2
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: minimal irritation (Kay and Calandra, 1962) see attached classification of eye score table
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
>= 4
Max. score:
20
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other:
Remarks:
mildly irritation (Kay and Calandra, 1962) see attached classification of eye score table
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
>= 2
Max. score:
20
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: minimaly irritation (Kay and Calandra, 1962) see attached classification of eye score table
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
>= 0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
>= 4
Max. score:
20
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: mildly irritation (Kay and Calandra, 1962) see attached classification of eye score table
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
>= 0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
>= 0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
>= 0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
>= 0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
>= 1
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
>= 1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: minimal irritation (Kay and Calandra, 1962) see attached classification of eye score table
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
>= 1
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
>= 0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
One hour after test substance instillation, minimal conjunctivitis was noted for all treated eyes.
There was no corneal opacity or iritis observed in any treated eye during this study. The overall
incidence and severity of irritation decreased with time. All animals were free of ocular irritation
by 72 hours (study termination). see attached table 3

Any other information on results incl. tables

All animals appeared active and healthy and gained body weight during the study. see attached table 2.

Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse clinical effects,

or abnormal behavior. Individual cage side observations in the attached table 1.

Applicant's summary and conclusion

Interpretation of results:
other: Not subject to classification under GHS
Conclusions:
Under the conditions of this study, E17-194T is considered as mildly irritating to the eye
Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for

E17-194T to produce irritation from a single instillation via the ocular route. Under the

conditions of this study, the test substance is classified as mildly irritating to the eye.

One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy

rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated

by the Draize method of scoring (Draize, Woodard, & Calvery, 1944; see Table 4).

One hour after test substance instillation, minimal conjunctivitis was noted for all treated eyes.

There was no corneal opacity or iritis observed in any treated eye during this study. The overall

incidence and severity of irritation decreased with time. All animals were free of ocular irritation

by 72 hours (study termination).