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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:
February 18, 1980 - March 3, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
non-GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Body weights were 2.0 to 3.5 kg
- Housing: Individually, according to the 'Guide for the care and use of laboratory anminals' (DHEW Publication no. (NIH) 78-23, 1978).
- Diet: daily 100 grams Purina Rabbit Chow supplemented by whole oats
- Water: ad libitum

ENVIRONMENTAL CONDITIONS: standard laboratory conditions

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Amount applied (volume or weight with unit): 0.1 mL into the right eye of each animal.
Duration of treatment / exposure:
Single instillation on day 1
Observation period (in vivo):
Eyes were examined before testing and at 24, 48 and 72 hours and at 4 and 7 days; any with persistent changes were examined again on day 10 and if needed also on day 15.
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
STUDY DESIGN
0.1 mL the test material was applied into the right eye of each of 6 animals.

TREATMENT
In accordance with OECD 405 (1981). The test substance is placed in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about one second. The other eye serves as control.

REMOVAL OF TEST SUBSTANCE
-Washing: No

SCORING SYSTEM
The primary occular irritation potential of the testing material was assessed with procedure of Draize, H.J. "Appraisal of the Safety of chemicals in foods, drugs and cosmetics", Assoc. of food and drug officials of the U.S., Austin, Texas (1959).

OBSERVATIONS
- Irritation: The eyes of each animal were examined approximately 24, 48 and 72 hours and 4 and 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. Additionally at 24 hours and 7 days, the eyes were examined with fluorescein stain under an UV light. Any persistent changes on day 7 were re-evaluated on day 10 using a hand held opthalmoscope and the fluorescein method. The irritation was assessed according to Draize as laid down in OECD 405 (1981).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
other: mean of 6 animals
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
other: fully reversible 1 on day 7, 3 on day 10, 1 on day 15, 1 judged irreversible at day 10
Remarks on result:
other: mean score per animal: 1.33/2/1/1/2/1.66
Irritation parameter:
iris score
Basis:
other: mean of 6 animals
Time point:
24/48/72 h
Score:
0.39
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score per animal: 0/0.33/0/0.66/0.66/0.66
Irritation parameter:
conjunctivae score
Basis:
other: mean of 6 animals
Time point:
24/48/72 h
Score:
1.61
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score per animal: 1.33/2/1.33/1/2/2
Irritation parameter:
chemosis score
Basis:
other: mean of 6 animals
Time point:
24/48/72 h
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: mean score per animal: 0.66/0/0/1/2/1.66
Irritant / corrosive response data:
All six animals developed opacity of the cornea within 24 hours after being dosed. Three rabbits had iritis at 48 hours and four at 72 hours. By Day 7 iritis had subsided in all rabbits and opacity had cleared in one eye. One rabbit had developed pannus. By Day 10 two rabbits still had opacity. In one there were ghost vessels and slight scarring adjudged irreversible. The second animal was retained until Day 15 at which time the opacity had cleared and the Draize score was 0.

Any other information on results incl. tables

Ocular Irritant response data (for the undiluted test substance)

  Time after administration
  24 hours 48 hours 72 hours Day 4 Day 7 Day 10 15 days
Animal number  1/2/3/4/5/6
Corneal Opacity 2/2/1/1/2/1 1/2/1/1/2/2 1/2/1/1/2/2 1/2/1/2/2/2 0/1/1/1/2/1  -/0/0/0/1/1  -/-/-/-/-/0
Cornea - Area 3/4/4/4/4/4 3/4/3/4/4/4 3/3/3/4/4/4 3/3/3/4/4/4 0/1/1/1/4/1  -/0/0/0/4/1  -/-/-/-/-/0
Iris 0/0/0/0/0/0 0/0/0/1/1/1 0/1/0/1/1/1 0/1/0/1/1/1 0/0/0/0/0/0  -/0/0/0/0/0  -/-/-/-/-/0
Conjunctivae               
 - Redness 2/2/2/1/2/2 1/2/1/1/2/2 1/2/1/1/2/2 1/2/1/1/2/2 0/0/0/0/0/0  -/0/0/0/0/0  -/-/-/-/-/0
 - Chemosis 1/0/0/0/2/2 1/0/0/1/2/2 0/0/0/2/2/1 0/0/0/2/2/1 0/0/0/0/0/0  -/0/0/0/0/0  -/-/-/-/-/0
 - Discharge  2/1/1/3/3/3 1/1/0/2/3/2 0/0/0/2/2/3 0/2/0/1/1/2 0/0/0/0/0/0  -/0/0/0/0/0  -/-/-/-/-/0
Control  0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0  -/0/0/0/0/0  -/-/-/-/-/0
Weighted score 40/46/26/28/54/34 21/46/17/33/59/57 17/39/17/35/57/57 17/43/17/53/55/55 0/5/5/5/40/5  -/0/0/0/20/5  -/-/-/-/-/0
Total 228 233 222 240 60 25 0
Primary ocular irritation score 38.00 38.83 37.00 40.00 10.00 4.17 0

Mean scores per animal over three timepoints (24-72 hours):

Corneal Opacity: 1.33/2/1/1/2/1.66: this means that 6/6 have a score >= 1 (CLP limit for classification as irritant, if at least in 2 of 3 animals)

Iritis: 0/0.33/0/0.66/0.66/0.66: this means that 0/6 have a score >= 1 (CLP limit for classification as irritant, if at least in 2 of 3 animals)

Redness: 1.33/2/1.33/1/2/2: this means that 3/6 animals have scores of >= 2 (CLP limit for classification as irritant, if at least in 2 of 3 animals)

Chemosis: 0.66/0/0/1/2/1.66: this means that 1/6 animals have a score of >= 2 (CLP limit for classification as irritant, if at least in 2 of 3 animals)

Applicant's summary and conclusion

Interpretation of results:
other: Serious Eye Damage, Category 1
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Under the conditions of this study, the mean eye irritation scores observed in the animals following grading at 24, 48 and 72 hours indicate an eye irritation potential. However, as in one animal irreversible effects were observed, Dimeth Cyclormol is considered to cause serious eye damage.
Executive summary:

Dimeth Cyclormol was tested in an eye irritation test in rabbits similar to OECD 405 but non-GLP and therefore scored Klimish 2. The right eye of six rabbits was treated with 0.1 ml of the undiluted test article.

Cornea opacity: Mean grade of 24, 48 and 72 hours is 1.5 (6/6 eyes scored >= 1; less than 4/6 eyes scored 3) indicating eye irritation. Opacity occurred within 24 hours after being dosed and one rabbit developed pannus. By day 10 two rabbits still had opacity. In one animal ghost vessels and slight scarring were adjudged irreversible and scoring was terminated. The opacity seen in the other animal had cleared by day 15.

Iris: Mean score during during 24 to 72 hours is 0.39 (less than 4/6 eyes scored 1). By day 7 iritis had subsided in all rabbits.

Conjuctivae: Mean score during 24 to 72 hours is 1.61 (less than 4/6 eyes scored 2).

Conjunctival chemosis: Mean score during 24 to 72 hours is 0.89 (less than 4/6 eyes scored 2).

In conclusion: Based solely on the scores the substance is an eye irritant. In view of the one animal showing irreversible effects, scar formation, the final conclusion is that the substance causes serious eye damage.