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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
Study period:
7 October 2009 - 17 November 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
zinc(2+) 3-hydroxypropane-1,2-bis(olate)
EC Number:
700-107-9
Cas Number:
87189-25-1
Molecular formula:
(C3H6O3Zn)n
IUPAC Name:
zinc(2+) 3-hydroxypropane-1,2-bis(olate)
Details on test material:
- Substance type: Organic
- Physical state: Powder
- Storage condition of test material: At room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain as stated in the report: New Zealand white Crl:KBL (NZW) SPF
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, 88353 Kisslegg
- Age at study initiation: ca. 9 months
- Weight at study initiation: 2300 - 2600 g
- Housing: individually in terulan cages
- Diet ad libitum: Ssniff K-H maintenance diet for rabbits
- Water ad libitum: tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated left eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 ml bulk volume (about 49 mg of the comminuted test item) into the right eye.
Duration of treatment / exposure:
24 h after single application into the conjunctival sac of the right eyelid the eye was rinsed with hand warm tap water.
Observation period (in vivo):
Readings were 1, 24, 48 and 72 h after application and on day 7 in 2/3 of the animals.
Mortality was checked twice each workday and once daily at weekends.
Since all effects were fully reversible within 7 days the study was discontinued thereafter.
Number of animals or in vitro replicates:
3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE:
- Washing: 24 h after treatment the treated eye was rinsed with hand warm tap water

EVALUATION:
For evaluation, the calculation of the mean values of corneal opacity, iris, conjunctival redness and chemosis for readings 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account. The evaluation is based on the criteria of the OECD Harmonized Integrated Classification System that was in place on the date of report signature (November 2009). In addition to specific observations recommended by the regulatory authorities, evaluations were made of discharge from the eye and the area of cornea affected by the lesions.

SCORING SYSTEM:
Cornea opacity:
Degree of density (the most dense area is taken for reading)
Grading
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent area, details of iris slightly obscured
3 Nacreous area, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of cornea involved (The assessment of these ocular reactions is performed independent of the quoted guidelines)
Grading
1 > 0 ≤ ¼, 2 > ¼ < ½, 3 > ½ < ¾, 4 > ¾

Iris:
Grading
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these observations or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae redness (Refers to palpebral and bulbar conjunctivae, not to cornea and iris):
Grading
0 Blood vessels normal
1 Some blood vessels definitely hyperaemic (injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse beefy red

Chemosis:
Lids and/or nictitating membrane
Grading
0 No swelling
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half closed
4 Swelling with lids more than half closed

Discharge (The assessment of these ocular reactions is performed independent of the quoted guidelines)
Grading
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs, and considerable area around the eye

Descriptions of any ocular findings not covered by this scale were recorded.

TOOL USED TO ASSESS SCORE:
otoscope lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
cornea opacity score
Basis:
other: animal # 2 and # 3
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.2
Max. score:
4
Remarks on result:
other: Corneal opacity was only seen in one animal.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable, since no effects on iris were seen
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1.3
Max. score:
4
Remarks on result:
other: All animals showed chemosis graded 4 after 1h, which decreased (grade 1 and 2) within 24 h.
Other effects:
Slight discharge (grade 1) was noted in all animals after 1 h, which disappeared after 48 h latest.
No clinical observations were reported in the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met