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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Toxi-Coop ZRT.

Test material

Constituent 1
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Thymidine

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult rabbits
- Weight at study initiation: 3200 - 3430 g
- Housing: Animals were housed individually in metal cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 25 days for the first animal, 26 days for the second animal, 27 days for the third animal

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70 %
- Photoperiod: 12 hours light, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES:
- From: 04 February 2013
To: 06 February 2013

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g
Duration of treatment / exposure:
The test item (finely ground) was placed into the conjunctival sac of left eye of each animal. The untreated right eye served as control. 0.1 g of the test item was used for the study in pure state, as a single dose. The eyes of the test animals were washed out 1 hour after test item application.
Observation period (in vivo):
Treated and control eyes were examined at 1, 24, 48 and 72 hours after the application.
Number of animals or in vitro replicates:
Three animals used sequentially.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: The eyes of the test animals were washed out with physiological saline solution (NaCl 0.9 %) 1 hour after test item application of, because the test item had not been removed from the eye of test animal by physiological mechanisms at the first observation time point.

SCORING SYSTEM
- The eye irritation scores were evaluated according to the scoring system by Draize (1979) and OECD 405 (02 October 2012)

TEST PROCEDURE
Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals with normal eye condition, any with ocular lesions were rejected.
In the first step an initial test was performed using one animal. The test item was placed into the conjunctival sac of the left eye. The eyelids were held closed gently for about one second to prevent any loss of the test item. The contralateral eye served as control.
In the initial test a slight irritant effect was observed 1 hour after treatment. The observed effect was fully reversible within 24 hours. The confirmatory test was conducted using a second animal. As in the first animal, slight irritant effects were observed 1 hour after treatment, but fully reversible within 24 hours. Following treatment of the second animal, the second confirmatory test was conducted using a third animal.
Again a slight irritant effect was observed 1 hour after the treatment. As in the first two animals effects were fully reversible within 24 hours.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Pre-existing test data
1. Determined physical-chemical properties and the chemical reactivity did not reveal potential corrosion/irritation effects to the eye.
2. A dermal toxicity test according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity) did not reveal any systemic toxicity effects up to the limit dose (2000 mg/kg bw). Further, no corrosion or severe irritation was noted (see Toxi-Coop ZRT. Study no. 698.321.3773).
3. An in vivo skin irritation test according to EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion) did not reveal any corrosion or irritation effects (see Toxi-Coop ZRT. Study no. 698.550.4157).
4. In a preceding in vitro test according to EU Method B.48 and OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants), no ocular corrosion or severe irritation potential was observed (see Toxi-Coop ZRT. Study no. 698.549.3770).
Based on the information available further in vivo testing for eye irritation/corrosion was carried out.
In vivo eye irritation/corrosion data
Treated and control eyes were examined at 1, 24, 48 and 72 hours after the application.
One hour after the treatment hyperemic blood vessels (score 1) were observed in treated eyes of all animals.
24 hours after the treatment all animals were free of symptoms.
48 hours after the treatment all animals were free of symptoms.
72 hours after the treatment all animals were free of symptoms.
72 hours after the treatment the study was terminated, as no primary irritation symptoms were observed.
During the study the control eyes of animals were symptom-free.
Acute Eye Irritation Study of
Test Item LZ3547 in Rabbits page 19 of 51
General state and the behaviour of animals were normal throughout the study period. No systemic toxicity including clinical signs of pain and distress were observed on the day of the treatment and during the 72-hour observation period.
Other effects:
There were no notable body weight changes during the contact and observation periods.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, the test item applied to the rabbits' eye mucosa caused slight conjunctival irritant effects after one hour, only. The slight redness observed was fully reversible within 24 hours. There were no signs of irritation observed 24, 48 and 72 hours.
Executive summary:

A study was carried out according to EU Method B.5, OECD Guideline 405 (Acute Eye Irritation / Corrosion) and OPPTS 870.2400. The testing of eye irritation/corrosion followed a tiered approach. Existing human and/or animal data, and/or in vitro data from validated and internationally accepted methods showing effects on eyes was assessed. All available information was evaluated to determine the need for in vivo eye testing.

Pre-existing data

Substance physical-chemical properties and chemical reactivity, a study on acute dermal toxicity according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity) and in vivo dermal irritation testing according to EU Method B.4 and OECD Guideline 404 (Acute Dermal Irritation / Corrosion) revealed no systemic toxicity or local effects, including corrosion or severely irritating properties. In a preceding in vitro test using the Isolated Chicken Eye model according to EU Method B.48 and OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants), no ocular corrosion or severe irritation potential was observed either.

Based on the information available further in vivo testing for eye irritation/corrosion was carried out.

Eye irritation data

The acute eye irritation study with the test item was performed in New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method (Draize, 1959; OECD Guideline 405, 2012).

The test item (finely ground) was placed into the conjunctival sac of left eye of each animal. The untreated right eye served as control. 0.1 g of the test item was used for the study in pure state, as a single dose. The eyes of the test animals were washed out 1 hour after test item application.

Treated and control eyes were examined at 1, 24, 48 and 72 hours after the application.

1 hour after the single application of the test item into the eye of the rabbits, slight redness was noted.

24 hours after treatment all animals were free of symptoms.

72 hours after treatment the study was terminated, as all animals were symptom free without signs of corrosion or irritation observed.

During the study the control eyes of animals were symptom-free.

No systemic toxicity was observed. The general state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation periods.

In conclusion, the test item applied to the rabbits' eye mucosa caused slight conjunctival irritant effects. However, the slight redness observed was fully reversible within 24 hours.