E17-194T, (P,P-diethyl, monoester with 1,2 propanediol)_

Endpoint summary

Description of key information

Primary eye irritation in Rabbits,

Primary skin irritation in Rabbits

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 18, 2017-January 2, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Originally, the test was carried out for the purpose of another regulation- Registration in the US- according to TSCA US EPA OPPTS 870.2500, Acute dermal irritation.
[EPA 712-C-98-196].

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Qualifier:

according to guideline

Guideline:

other: JMAFF 12-Nousan-8147 (2000)

GLP compliance:

yes

Specific details on test material used for the study:

Composition: 100%
Physical description: Clear transparent liquid
Stability: Test substance was expected to be stable for the duration of the study
Expiration date: November 3, 2020

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or test system and environmental conditions:

Number of animals: 3
Sex: Female, nulliparous and non-pregnant
Species/strain: Rabitt/New Zealand albino
Age/body weight: Young adults (13-14 weeks)/ 2641-2976 gr at experimental start
Source: Received from Robinson Services Inc. on Nov 15 and Dec. 13, 2017
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: 19-23"C and 42-53%,
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: 13 or 33 days
Food: Envigo Teklad Global High Fiber Rabbit Diet® #2031. A designated amount
of the diet (approximately 150 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Five-tenths of a mililiter of the material was applied to the skin of each dose.

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

30-60 min after patch removal after the appropriate patch removal and subsequent evaluations were performed approx. 24, 48, 72 hr after removal of the four-hour patch.

Number of animals:

3

Details on study design:

PROCEDURE
Preparation and selection of animals: On the day before application, a group of animals was prepared by clipping the dorsal area of the trunk.
On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healty, naive animals (not previously tested) without pre-existing skin irritation were selected for test. Initially, only one rabbit was placed on test. Since no significant dermal irritation was observed at the dose sites on this animal, the test was completed with two additional rabbits.
Preparation of test substance: The test substance was applied and mixed well prior to use. The pH was determined for the test substance prior to the application and was within the pH range of 2 and 11.5., therefore testing proceeded. The procedure used and the results are retained in the raw data.
Application of test substance: Initial testing was conducted on one rabbit to determine the irritation/corrosion potential of the test substance. Three dose site, each approximately 6-cm2, were delieated on this raddit. Five-tenths of a mililiter of the test substance was applied to the skin of each dose site and covered with 1-inch x 1-inch, 4-ply qauze pad. The pads and entire trunk of animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the patches. An Elizabethan collar was placed on the rabbit after removal of the 3-minute patch and it was returned to its designated cage. The pads were removed at the appropriate intervals (3 minutes, 1 hour and 4 hours). All dose sites were evaluated for corrosion 30-60 minutes after patch removal. Subsequent evaluations were performed approximately 24, 48, 72 hours after removal of the four hour patch. Since there was no corrosion observed at any of the dose sites for this animal, two additional rabbits (each with one patch only for a 4- hour exposure period), were selected for further testing and treated in the same manner as described above with an additional evaluation at 7 days.
After the 3-minute and 1-hour exposure periods, the pads were removed and the dose sites were cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.
After the 4-hour exposure period, the pads and collars were removed and the dose sites were cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.
Evaluation of dose sites: indevidual dose sites were scored according to the Draize scoring system at approximately 30-60 minutes, 24, 48 and 72 hours and/or 7 days after patch removal in addition to evaluation for corrosion at these intervals for the first animal only.
The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minute, 24, 48 and 72-hour scoring and dividing by the number of evaluation intervals.
the resulting Primary Dermal Irritation Index (PDII) was classified as follows:
PDII Classification
0 Non-irritating
>0-2.0 Slightly irritating
2.1-5.0 Moderately irritating
> 5.0 Severly irritaiting

Cage side Observations: The animals were observed for signs of gross toxicity and behavioral changs at least once daily during the test period.
Body weights: Individual weights of animals were recorded shortly before application of the test substance (initial) and at the completion of testing (terminal).
Study termination: Once testing was complete, the animals were released for euthanasia and humanely euthanized.
Statistical analysis was limited to the calculation of the mean irritation score.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: PDI for 30-60 min, 24, 48 and 72 hr

Score:

ca. 0.7

Reversibility:

other: Edema within 24 hr, Erythema within 7 days

Remarks on result:

other: slightly irritating

Irritation parameter:

erythema score

Remarks:

3 minute exposre

Basis:

animal #1

Time point:

other: 30-60 min after patch removal

Score:

1

Irritation parameter:

erythema score

Remarks:

3 minute exposure

Basis:

animal #1

Remarks:

time after removal 4 hr patch

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 24 hr

Irritation parameter:

erythema score

Remarks:

1 hr exposure

Basis:

animal #2

Time point:

other: 30-60 min after patch removal

Score:

0

Irritation parameter:

erythema score

Remarks:

1 hr exposure

Basis:

animal #2

Remarks:

time after removal 4 hr patch

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #3

Time point:

other: 30-60 min after patch removal

Score:

1

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 48 hr

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #4

Time point:

other: 30-60 min after patch removal

Score:

1

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #4

Time point:

24/48 h

Score:

0

Max. score:

1

Reversibility:

not fully reversible within: 48 hr

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #4

Time point:

other: 72 hr / 7 d

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 7d

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #5

Time point:

other: 30-60 min after patch removal

Score:

1

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 24 hr

Irritation parameter:

erythema score

Remarks:

4 hr exposure

Basis:

animal #5

Time point:

7 d

Score:

0

Irritation parameter:

edema score

Remarks:

3 minutes exposure

Basis:

animal #1

Time point:

other: 30-60 min after patch removal

Score:

0

Irritation parameter:

edema score

Remarks:

3 minute exposure

Basis:

animal #1

Remarks:

time after removal of 4 hr patch

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Remarks:

1 hour exposure

Basis:

animal #2

Time point:

other: 30-60 min after patch removal

Score:

0

Irritation parameter:

edema score

Remarks:

1 hour exposure

Basis:

animal #2

Remarks:

time after removal of 4 hr patch

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Remarks:

4 hour exposure

Basis:

animal #3

Time point:

other: 30-60 min after patch removal

Score:

1

Irritation parameter:

edema score

Remarks:

4 hr exposure

Basis:

animal #3

Remarks:

time after patch removal

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 24 hr

Irritation parameter:

edema score

Remarks:

4 hour exposure

Basis:

animal #4

Remarks:

time after patch removal

Time point:

other: 30-60 min

Score:

1

Irritation parameter:

edema score

Remarks:

4 hour exposure

Basis:

animal #4

Remarks:

time after patch removal

Time point:

other: 24/48/72 hr and 7 d

Score:

0

Reversibility:

fully reversible within: 24 hr

Irritation parameter:

edema score

Remarks:

4 hour exposure

Basis:

animal #5

Remarks:

time after patch removal

Time point:

other: 30-60 min, 24 hr / 48 hr / 72 hr / 7 d

Score:

0

Irritant / corrosive response data:

No visible necrosis (corrosion) of the skin tissue was observed at the 3-minute, 1-hour and 4-hour dose sites during the study.

Other effects:

All animals appeared active and healty and gained body weight during the study. There were no other signs of gross toxicity, adverse clinical effects, or abnormal behavior.

3 -minute exposure site:

Very slight erythema was observed at the dose site within 30 -60 minutes after patch removal, which resolved by 24 hours for the first animal.

1 -hour exposure site:

No dermal irritation was noted at the 1 -hour exposure site for the first animal

4 -hour exposure site:

Within 30 -60 minutes of patch removal, all three treated sites exhibited very slight erythema and/or very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by day 7 (study termination)

Interpretation of results:

GHS criteria not met

Conclusions:

The primary Dermal Index for this substance is 0.7.
Under the conditions of the study, E17-194T is slightly irriating to skin.

Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential for E17 -194T to produce irritation after a single topical application.

initially one rabbit was tested, to determine the irritation/corrosion of the test substance. Three dose sites, each approx. 6 -cm2, were delineated on this animal. 5/10 of a mililiter were applied to the skin of each dose site. The pads and entire trunk of the animal were wrapped with semi occlusive 3 -inch Micropore tape. The patches were removed at the appropriate intervals (3 min, 1hr and 4 hr). All dose sites were evaluated according to Draize method of scoring.

Results: The primary Dermal Index for this substance is 0.7. Under the conditions of the study, E17-194T is  slightly irriating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

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)

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

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.

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

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

not subject to classification under GHS