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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)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 01805 1216
- Expiration date of the lot/batch: 03 2018
- Purity test date: 03 2017

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: 11-12 weeks old
- Weight at study initiation: 2906-3220 g
- Housing: animals were housed individually in metal cage
- Diet (e.g. ad libitum): S&K LAP rabbbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11-12-13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3
- Humidity (%): 30-70 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12-12

Test system

Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the test item was used for the study in undiluted form, as a single dose.
Duration of treatment / exposure:
The eyes of the test animals were not washed out 24 hour after test item application, because the test item had been removed from the eye of test animal by physiological mechanisms.
Observation period (in vivo):
3 weeks
Number of animals or in vitro replicates:
3
Details on study design:

SCORING SYSTEM: Draize (1959) and OECD 405 (24 April 2002)

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 1,2,3
Time point:
24/48/72 h
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
conjunctivae score
Basis:
animal: 1,2,3
Time point:
24/48/72 h
Score:
>= 0 - <= 3
Max. score:
3
Reversibility:
fully reversible within: 3 weeks
Irritant / corrosive response data:
Treated and control eyes were examined at 1, 24, 48 and 72 hours then 1, 2 and 3 weeks after the application.
One hour after treatment some hyperemic blood vessels (score 1) were observed in all animals. The swelling of the conjunctivae was different from normal (score 1) in two animals (No.: 774, 785). Discharge with moistening of the lids and hairs just adjacent to lids (score 2) was recorded in animal No.: 790. Diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in animal No.: 785. The area of cornea involved was greater than three quarters, up to the whole area (score 4).
24 hours after treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2), the swelling of the conjunctiva with lids about half closed (score 3) and the discharge of the conjunctivae moistened lids and hairs on considerable area around the treated eye (score 3) were recorded in two animals (No.: 774, 785). Besides, easily discernible translucent areas of the cornea were found and the details of iris were slightly obscured (score 2) in same animals. The area of cornea involved was greater than three quarters, up to the whole area (score 4). Animal No.: 790 became free of symptoms.
48 hours after treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) and the swelling of the conjunctiva with lids about half closed (score 3) were observed in two animals (No.: 774, 785). Discharge of the conjunctivae moistened lids and hairs on considerable area around the treated eye (score 3) were recorded in animal No.: 774. Discharge with moistening of the lids and hairs just adjacent to lids (score 2) was detected in animal No.: 785. Easily discernible translucent areas of the cornea were found and the details of iris were slightly obscured (score 2) in two animals (No.: 774, 785). The area of cornea involved was greater than three quarters, up to the whole area (score 4). Besides, another sign as pinkish discharge around the eye was observed in two animals (No.: 774, 785). Animal No.: 790 was free of symptoms.
72 hours after treatment some hyperemic blood vessels (score 1) were observed in animal No.: 774. Diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) was recorded in animal No.: 785. The swelling of the conjunctiva with lids about half closed (score 3) was detected in animal No.: 774 and the swelling of the conjunctivae was different from normal (score 1) in animal No.: 785. Discharge of the conjunctivae moistened lids and hairs on considerable area around the treated eye (score 3) was recorded in animal No.: 774.
slightly obscured (score 2) in animal No.: 774 and diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in animal No.: 785. The area of cornea involved was greater than three quarters, up to the whole area (score 4) in both animals. Animal No.: 790 was free of symptoms.
1 week after treatment some hyperemic blood vessels (score 1) were observed in two animals (No.: 774, 785). The swelling of the conjunctivae was different from normal (score 1) in animal No.: 774. Discharge of the conjunctivae moistened lids and hairs on considerable area around the treated eye (score 3) was recorded in animal No.: 774. Diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in animal No.: 774. The area of cornea involved was greater than half, but less than three quarters (score 3).
2 weeks after treatment some hyperemic blood vessels (score 1) were observed in animal No.: 774. The swelling of the conjunctivae was different from normal (score 1) in animal No.: 774. Diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in animal No.: 774. The area of cornea involved was greater than half, but less than three quarters (score 3). Two animals (No.: 785, 790) were free of symptoms.
3 weeks after the treatment the study was finished, because all animals were free of symptoms.
During the study the control eyes of animals were symptom-free.
Detailed eye irritation results are shown in Appendix I.
The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
cornea opacity : 2.00, 1.66, 0.00
iris : 0.00, 0.00, 0.00
redness : 1.66, 2.00, 0.00
chemosis : 3.00, 2.33, 0.00
discharge : 3.00, 1.66, 0.00
No systemic toxicity was observed on the day of the treatment and during the 21-day observation period. The body weight of animals corresponded to their species and age. Sign of pain and distress as discharge was observed in all animals between the treatment day and Day 9.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
In conclusion, test item 3,4-O-dimethyl methyldopa monohydrochloride monohydrate (DMAKS) applied to the rabbits' eye mucosa caused slight to severe conjunctival and slight to moderate cornea irritant effects which were fully reversible within 3 weeks.
On basis of the conjunctivae irritation sign as chemosis observed in animals, the test item should be classified as “R36 – Irritating to eyes” according to Directive 2001/59/EC.
According to Regulation (EC) No. 1272/2008, the test item should be classified into “Category 2 (reversible effects on the eye/irritating to eyes)” on basis of conjunctivae irritation sign as chemosis and cornea opacity.