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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:
10 April 2009 to 14 April 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Daltolac XR 159
- Lot/batch No.: RZW023
- Physical Description: Light yellow viscous liquid
- Composition/Purity: Reaction mass of 2,2'-Oxydiethanol, propoxylated and formaldehyde polymer with benzenamine and 2-methyloxirane
Stability: The test article was expected to be stable under standard laboratory conditions for the duration of testing.
Storage Conditions: Room temperature (10-30ºC)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
Total Number: Three
Gender: Female
Age Range: 12 weeks at start of dosing; records of dates of birth for animals used in this study are retained in the Calvert archives.
Body Weight Range: 2.4 to 2.5 kilograms at the outset (Day 1) of the study.
Animal Source: Harlan, Oxford, MI
Experimental History: Purpose-bred and experimentally naïve at the outset of the study.
Identification: Ear tag and cage card

ENVIRONMENTAL CONDITIONS
Housing: Animals were individually housed in compliance with USDA Guidelines. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
Lighting: 12 hours light/12 hours dark
Room Temperature: 16.7 to 21°C
Relative Humidity: 26 to 58%
Food: All animals had access to PMI Rabbit Diet (certified) as per Calvert SOP. The lot number(s) and specifications of each lot used are archived at Calvert. No contaminants were known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which are maintained in the Calvert archives.
Water: Tap water was available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP’s. No contaminants were known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis are maintained in the Calvert archives.
Acclimation: Study animals were acclimated to their housing for a minimum of 5 days prior to dosing.

IN-LIFE DATES: From: 10 April 2009 To: 14 April 2009

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
The test article was administered once, directly into the eye (conjunctive sac).
A dose of 0.1 ml of the liquid was instilled into the right eye of each rabbit.
Duration of treatment / exposure:
Once
Observation period (in vivo):
prior to dose, and at 1, 24, 48 and 72 hours post-dose and on Day 5.
Number of animals or in vitro replicates:
Three
Details on study design:
The primary skin irritation study was initiated prior to this study. Since the pH of the test material was 6 and the test article was not found to be severely irritating or corrosive to the skin of any rabbit, this study was conducted. In the interest of animal welfare, based on the results of the primary skin irritation study and at the discretion of the Study Director and Calvert DLAM, one animal was dosed and evaluated at one hour post-dose before the remaining two animals were dosed.
Within 24 hours before administration of the test article, both eyes were examined. All animals placed on study were found acceptable.
Each animal received 0.1 ml of undiluted liquid test article. A pre-anesthetic was applied to both eyes of each rabbit. The preanesthetic was 2 drops of Tetracaine applied to the corneal surface approximately 5 minutes prior to dose application. The test article was placed in the conjunctive sac of the right eye in one animal after gently pulling the lower lid away from the eyeball. The lid were then gently held together for approximately one second in order to limit loss of the material. One animal was dosed and evaluated at one hour post-dose before the remaining two animals were dosed. The eyes of the three rabbits remained unrinsed after instillation of the test article. The right eye of each animal was treated with the test article and the left eye served as the untreated control.
Since there were no adverse reactions after administration of the test article to the first animal, or at the 1-hour examination a severe reaction was not observed in the treated eye of any of the animals, the treated animals were maintained on study. The scores of both eyes were documented in the raw data.

Scoring system: An animal has exhibited a positive reaction if the test substance has produced at any observation one or more of the following signs:
opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae of a light hyperemia of the circumcorneal blood vessels) or an observatons swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids or a diffuse crimson colour with individual vessels not easily discrenible.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour post-dose
Score:
11.7
Max. score:
110
Reversibility:
fully reversible within: 5 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
9.3
Max. score:
110
Reversibility:
fully reversible within: 5 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hours
Score:
4.7
Max. score:
110
Reversibility:
fully reversible within: 5
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 hours
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 5 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Same result for all 3 animals
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Other effects:
none

Any other information on results incl. tables

Body weight data are presented in the table below:

Animal No.

Initial body weight

Final body weight

2913F

2.4

2.6

2914F

2.5

2.7

2915F

2.5

2.6

Ocular Observations/Post Treatment - Right Eye
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2913 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 1 0 0 0 0
  Ax5= 0 5 0 0 0 0
  Conjunctivae            
  A. Redness 0 1 1 1 1 0
  B. Chemosis 0 1 0 0 0 0
  C. Discharge 0 3 3 2 1 0
  (A+B+C)x2= 0 10 8 6 4 0
               
  Total Score 0 15 8 6 4 0
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2914 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 0 0 0 0 0
  Ax5= 0 0 0 0 0 0
  Conjunctivae            
  A. Redness 0 1 1 0 1 0
  B. Chemosis 0 1 0 0 0 0
  C. Discharge 0 3 3 2 1 0
  (A+B+C)x2= 0 10 10 4 2 0
               
  Total Score 0 10 10 4 2 0
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2915 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 1 0 0 0 0
  Ax5= 0 5 0 0 0 0
  Conjunctivae            
  A. Redness 0 1 1 0 0 0
  B. Chemosis 0 1 1 0 0 0
  C. Discharge 0 3 3 2 0 0
  (A+B+C)x2= 0 10 10 4 0 0
               
  Total Score 0 10 10 4 6 0
TOTAL GROUP SCORE   0 35 28 14 6 0
GROUP MEAN SCORE   0 11.7 9.3 4.7 2 0
Ocular Observations/Post Treatment - Left Eye
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2913 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 0 0 0 0 0
  Ax5= 0 0 0 0 0 0
  Conjunctivae            
  A. Redness 0 0 0 0 0 0
  B. Chemosis 0 0 0 0 0 0
  C. Discharge 0 0 0 0 0 0
  (A+B+C)x2= 0 0 0 0 0 0
               
  Total Score 0 0 0 0 0 0
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2914 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 0 0 0 0 0
  Ax5= 0 0 0 0 0 0
  Conjunctivae            
  A. Redness 0 0 0 0 0 0
  B. Chemosis 0 0 0 0 0 0
  C. Discharge 0 0 0 0 0 0
  (A+B+C)x2= 0 0 0 0 0 0
               
  Total Score 0 0 0 0 0 0
Animal#   Pre-Dose 1h 24h 48h 72h Day5
2915 F Cornea            
  A. Opacity-Degree 0 0 0 0 0 0
  B. Are Involved 0 0 0 0 0 0
  Axbx5=            
  Iris            
  A. Values 0 0 0 0 0 0
  Ax5= 0 0 0 0 0 0
  Conjunctivae            
  A. Redness 0 0 0 0 0 0
  B. Chemosis 0 0 0 0 0 0
  C. Discharge 0 0 0 0 0 0
  (A+B+C)x2= 0 0 0 0 0 0
               
  Total Score 0 0 0 0 0 0
TOTAL GROUP SCORE   0 0 0 0 0 0
GROUP MEAN SCORE   0 0 0 0 0 0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on the EEC and GHS criteria, Daltolac XR 159 was determined to be a non-irritant.
Executive summary:

The purpose of this study was to determine the potential irritant and/or corrosive effects of the test article on eyes of rabbits.

The test article, Daltolac XR 159, was administered (0.1 ml) into the conjunctival sac of the right eye of three New Zealand White rabbits. Upon instillation, the eye was held closed for approximately 1 second to prevent loss of material. The left eye of each animal served as an untreated control. Both eyes of all animals were examined and scored for ocular irritation prior to dose and at 1, 24, 48 and 72 hours post-dose and on Day 5.   

In the animals receiving Daltolac XR 159, iritis was observed in one of three rabbits at 1 hour post treatment. Scores for conjuctival redness, chemosis and/or discharge were observed at 1, 24, 48 and/or 72 hour post-dose. There was no irritation present on Day 5 and the in-life study was terminated.