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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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Name: Ethanol, 2,2'-oxybis-, reaction products with ammonia, morpholine derivs. residues
Physical state: liquid
Appearance: brown liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Amine C8
- Substance type: no data
- Physical state: viscous amber liquid
- Storage condition of test material: 15-30 °C, room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan or any other USDA approved vendor
- Age at study initiation: young adult (12-18 weeks) at start of dosing; records of dates of birth for animals used in this study will be retained in the Calvert archives.
- Weight at study initiation: 2.0-3.0 kilograms at the outset (Day 1) of the study.
- Housing: Animals are housed individually in compliance with USDA Guidelines. The room in which the animals will be kept will be documented in the study records. no other species will be kept in the same room.
- Diet (e.g. ad libitum): All animals will have access to PMI certified Hi-Fiber Rabbit Diet or equivalent as per Calvert SOP, unless otherwise specified. The lot number and specifications of each lot used are archived in the facility records at Calvert. No contaminants are 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 will be maintained in the Calvert archives.
- Water (e.g. ad libitum): Tap water is 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 are 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 will be maintained in the Calvert archives.
- Acclimation period: study animals were acclimated to their housing for a minimum of seven days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 21°C
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL


Duration of treatment / exposure:
Only once instilled
Observation period (in vivo):
mortality/morbidity: once daily
clinical observations: prior to dose administration and then daily
ocular observations: at 1 (± 15 minutes), 24, 48 and 72 hours (± 1 hour); if there is no evidence of irritation at 72 hours, the study will be complete. Extended observations may be necessary if there is persistent corneal involvement or other ocular irritation is observed to determine the progress of the lesions and their reversibility or irreversibility. If the cornea, iris or conjunctivae have not healed completely by Day 8, the unhealed animals will be retained and reexamined on Days 15 and 22, if injury persists. In addition to the observations of the cornea, iris and conjunctivae, any other lesions, which are noted, will be recorded and reported. The grades of ocular reaction according to Draize will be manually recorded at each examination.
Body weight: prior to dose administration
Number of animals or in vitro replicates:
Three
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of the animals will remain un-rinsed for at least 24 hours after instillation of the test article. The treated eyes may be gently washed out (if necessary) using room temperature physiological saline.
- Time after start of exposure: see above

SCORING SYSTEM: An animal has exhibited a positive reaction if the test article 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 or light hyperemia of the circum corneal blood vessels) or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids or a diffuse crimson color with individual vessels not easily discernible.
EEC classification of ocular irritants: The total ocular irritation score for the 24, 48 and 72 hour invertvals are individually added for corneal opacity, iris lesion, conjunctival redness and conjunctival edema. For a group of the three animals, the calculated mean scores will remain expressed individually and compared to the EEC ocular evaluation criteria. Scores for two or more animals above the appropriate mean will classify the test article in that particular category. A test substance will be classified as a nonirritant, irritating to the eyes (R36) or risk of serious damage to eye (R41 Risk Phrase) based on the EEC Ocular Evaluation Criteria.

Globally harmonized system of classification evaluation criteria: for this classification system, the 24-, 48- and 72- hours scores will be added separately for each animal and each total divided by 3 (three time points) to yield the individual mean scores for each animal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24 hours post dose
Score:
26
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48 hours
Score:
31
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72 hours
Score:
32.67
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: day 5
Score:
30.67
Max. score:
110
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 8 days
Score:
28.67
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
4
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0.67
Max. score:
4

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the data of this EPA OPPTS 870.2400 and EC Method B.5 study and according to the criteria of the CLP Regulation, the test substance is classified as irritating to eyes (category 2).