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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:
Initiation date: October 7, 1980; Termination date: October 14, 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): EHS-152
- Physical state: Clear, colourless liquid:
- Lot/batch No.: B-0228 (8-18-80)
- Storage condition of test material: Room temperature in a locked test compound cabinet

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: J & J Research Farms, Hamilton, Ohio
- Age at study initiation: Young adult
- Weight at study initiation: Body weights ranged from 2.10 to 2.35 kg
- Housing: The rabbits were individually housed in wire-bottomed cages suspended above the droppings.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow, 5322 were offered ad libitum
- Water (e.g. ad libitum): Water offered ad libitum
- Acclimation period: The rabbits were quarantined and acclimated to laboratory conditions for 7 days prior to initiation of the study. Animals were observed twice daily during the quarantine period. Approximately 24 hours prior to application of the test material both eyes of each animal in the test group were examined using fluorescein dye procedures. All animals employed in this study were without eye defects or irritation.

ENVIRONMENTAL CONDITIONS
Room conditions, as well as availability of adequate food and water, were checked and any noteworthy conditions recorded.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL:
Exactly 0.1 ml of the undiluted test material was instilled.
Duration of treatment / exposure:
SIngle application.
Observation period (in vivo):
Grading for irritation and injury were made at 1, 24, 48 hours and at 4 and 7 days.
Number of animals or in vitro replicates:
A total of nine rabbits were used (6 not rinsed and 3 rinsed).
Details on study design:
Experimental Design:
The study utilized one dose level (0.1 ml) administered to the right eye of each rabbit, the left eye served as the untreated control.

Test Material Administration:
Exactly 0.1 ml of the undiluted test material was instilled with a sterile syringe in the right eye of each animal by gently pulling the lower lid (conjunctival cul-de-sac) away from the eyeball to form a cup into which the test substance was dropped. Following instillation of the test material the eye lids were held closed for 1 second and then released. Thirty seconds after instillation of the test material, the treated eyes of 3 rabbits were gently held open and irrigated with three 60 cc syringes filled with lukewarm water for one minute.

Bofy Weights:
All animals selected for the study were weighed on the day of exposure and on the day of termination.

Observations and Mortality:
All animals were observed closely for gross signs of systemic toxicity and mortality at frequent intervals during the day of dosing and at least twice daily thereafter for a total of 8 days.

Necropsy;
All animals were sacrificed by Euthanasia T-61 and a gross necropsy performed on the visceral and thoracic cavities.

SCORING SYSTEM:
Grading for irritation and injury were made at 1, 24, 48 and 72 hours and at 4 and 7 days, using the standard scoring system of Draize (see Table 1 in attached background material).

Fluoroscein examinations were used to facilitate evaluation of potential corneal damage.

Calculation of the Acute Eye Irritation Index:
The maximum score at any one time examination and scoring period is 110 points which indicates maximal irritation and damage to all three ocular tissues, zero score indicates no irritation. Mean value scores were calculated and used to determine the primary irritation index and assing a classification based upon the values presented in Table 2 (see attached background material).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Primary Irritation Index
Basis:
mean
Remarks:
(based on conjuctiva)
Time point:
other: 4 Day
Score:
0.33
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Primary Irritation Index for non rinsed animals
Irritation parameter:
other: Primary Irritation Index
Basis:
mean
Remarks:
(based on conjuctiva)
Time point:
other: 1 hour
Score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Primary Irritation Index for rinsed animals
Irritant / corrosive response data:
Individual eye irritation scores and means are presented in Table 3 (see attached background material). Positive scored noted involved the conjunctiva varying in degrees of redness, chemosis, and discharge at day 4 for one not rinsed animal and at 1 hour for all three rinsed animals. No signs of corneal damage were noted upon fluorescein examinations.

A summary of the mean scores and the primary eye irritation index is presented in Table 4 (see any other information on results incl. tables). For non-rinsed animals a score at day 4 of 0.33, using the Draize method, classifies EHS-152 as non-irritating.
For rinsed animals a score at 1 hour of 2.0, using the Draize method, was obtained and classifies the substance as practically non-irritating.
Other effects:
Body Weight and Weight Change Data:
Body weights at the termination of the study ranged from 2.30 to 2.60 kilograms. Body weights gains appeared normal.

Observations and Mortality:
No animal exhibited signs of systemic toxicity and no deaths occurred during the investigation.

Necropsy:
Examinations of the thoracic and visceral cavities of the test animals at necropsy revealed no significant findings.

Any other information on results incl. tables

Table 4

 

Not rinsed (6 animals)

 

Tissue

Examination Intervals

1 hr

24 hr

48 hr

72 hr

4 day

7 day

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

0

0

0

0

2

0

Total

0

0

0

0

2

0

Mean

0

0

0

0

0.33

0

 

Primary Eye Irritation Index = 0.33

 

Rinsed (3 animals)

 

Tissue

Examination Intervals

1 hr

24 hr

48 hr

72 hr

4 day

7 day

Cornea

0

0

0

0

0

0

Iris

0

0

0

0

0

0

Conjunctiva

6

0

0

0

0

0

Total

6

0

0

0

0

0

Mean

2

0

0

0

0

0

 

Primary Eye Irritation Index = 2

                                                                                

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
When EHS-152 was instilled into one eye of each of nine albino rabbits (6 not rinsed and 3 rinsed). No signs of systemic toxicity or mortality were observed and the primary irritation index of 0.33 classifies EHS-152 as non-irritating. Irrigation with water increased the score to 2.0 at 1 hour and the classification to practically non-irritating.
Based on the results the substance does not meet the criteria for classification according to CLP.
Executive summary:

The objective of the study was to determine the irritative potential of the test material following a single dose to the eye of albino rabbits.

The study utilized one dose level (0.1 ml) administered to the right eye of each rabbit, the left eye served as the untreated control. A total of nine rabbits were used (6 not rinsed and 3 rinsed).

When EHS-152 was instilled into one eye of each of nine albino rabbits (6 not rinsed and 3 rinsed). No signs of systemic toxicity or mortality were observed and the primary irritation index of 0.33 classifies EHS-152 as non-irritating. Irrigation with water increased the score to 2.0 at 1 hour and the classification to practically non-irritating.

Based on the results the substance does not meet the criteria for classification according to CLP.