Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 04 to April 01, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted similarly to OECD guideline 405 with only minor deviations: no data on purity and bodyweights not followed
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
yes
Remarks:
no data on purity and bodyweights not followed
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no data on purity and bodyweights not followed
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Desiccant L-10
- Source: Pennwalt Corporation, USA
- Physical state: Light blue, clear liquid
- Date of receipt: January 4, 1985
- Lot/batch No.: 8158
- Storage condition of test material: Room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland, Inc., Denver, USA
- Age at study initiation: Young adults
- Housing: Individually housed in suspended, stainless steel cages
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326), ad libitum
- Water (e.g. ad libitum): Municipal water supply (Elizabethtown Water Co.), ad libitum
- Acclimation period: 35 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70 °F
- Humidity (%): 30-70%
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Both eyes of 3 rabbits were washed after 20 sec; the eyes of the 6 others were not rinsed
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
Nine (8 males, 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated and control eyes of six animals remained unwashed. Twenty seconds after the test substance was administered, both eyes of the remaining three animals were rinsed for one minute with lukewarm tap water.

SCORING SYSTEM: Draize scoring system (1959)

TOOL USED TO ASSESS SCORE: Fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
3.4
Max. score:
4
Reversibility:
not reversible
Remarks:
all animals died within 9 days
Remarks on result:
other: eyes unwashed
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
1.4
Max. score:
2
Reversibility:
not reversible
Remarks:
all animals died within 9 days
Remarks on result:
other: eyes unwashed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
1.54
Max. score:
3
Reversibility:
not reversible
Remarks:
all animals died within 9 days
Remarks on result:
other: eyes unwashed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
2.27
Max. score:
4
Reversibility:
not reversible
Remarks:
all animals died within 9 days
Remarks on result:
other: eyes unwashed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
4
Reversibility:
other: reversible in one animal within 14 days; irreversible in 2 animals within 21 days
Remarks on result:
other: eyes washed
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
1.1
Max. score:
2
Reversibility:
other: reversible in one animal within 14 days; irreversible in 2 animals within 21 days
Remarks on result:
other: eyes washed
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
2.4
Max. score:
3
Reversibility:
other: reversible in one animal within 14 days; irreversible in 2 animals within 21 days
Remarks on result:
other: eyes washed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
all animals
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
4
Reversibility:
other: reversible in one animal within 14 days; irreversible in 2 animals within 21 days
Remarks on result:
other: eyes washed
Irritant / corrosive response data:
- Desiccant L-10 produced severe ocular irritation in all animals.
- All nine animals exhibited moderate to severe conjunctival irritation (redness, chemosis, discharge), conjunctival necrosis, iridial damage and extensive corneal opacity and/or ulceration. - Effects were slightly less severe in the washed eyes. 1/3 animal was free of ocular irritation within 14 days post-instillation. Remaining animals continued to exhibit severe irritation (including corneal opacities) at termination of the study (Day 21).
- All animals with non-washed eyes had severe irritation prior to being found dead or prior to sacrifice for humane reasons on Day 9.
- Other signs of severe irritation seen in some animals included pannus (neovascularization of the cornea) bulging of the cornea (considered indicate of intraocular pressure), the presence of white fluid in the anterior chamber, a dark red band in the iris and blue or white discoloration of the iris.
Other effects:
- Mortality: 3/6 rabbits with non-washed eyes were found dead on Days 1, 5 or 7. Surviving animals in this group were killed on Day 9 for humane reasons because of severe ocular effects. All three animals with washed eyes survived throughout the study.
- Clinical signs of toxicity: All animals with non-washed eyes exhibited decreased food consumption. One animal which died exhibited coarse tremors, prostration and hypothermia. No unusual signs were seen in animals with washed eyes.
- Necropsy: One animal, which died on Day 7, had discoloration of the lungs and liver and a number of gastrointestinal lesions; other observations revealed evidence of autolytic changes and/or antemortem stress.

Any other information on results incl. tables

Table 1: Individual eye irritation scores

 

Animal

Time after dosing

Conjunctivae

Iris

Corneal opacity

Redness

Chemosis

6123 M

1 hour

0

2

+

3

24 hours

1

2

1

3

48 hours

1

2

1

3

72 hours

1

2

2

3

Day 7

3

2

2

4

Day 10*

 

Mean (24, 48 and 72 hours)

1

2

1.3

3

6125 M

1 hour

1

3

1

3

24 hours

1

2

1

3

48 hours

2

2

1

3

72 hours

1

2

1

3

Day 7*

 

Mean (24, 48 and 72 hours)

1.3

2

1

3

6126 F

1 hour

0

2

Ne

4

24 hours

1

2

1

4

48 hours

NC

2

2

4

72 hours

NC

3

2

4

Day 7

3

2

2

4

Day 10*

 

Mean (24, 48 and 72 hours)

2.3

2.3

1. 7

4

6127 M

1 hour

1

2

1

3

24 hours

1

3

Ne

4

48 hours

1

3

2

4

72 hours

2

3

2

4

Day 7

3

2

2

4

Day 10*

 

Mean (24, 48 and 72 hours)

1.3

3

2

4

6128 M

1 hour

1

3

1

3

24 hours

1

2

1

3

48 hours

2

2

1

3

72 hours

2

2

1

3

Day 7*

 

Mean (24, 48 and 72 hours)

1.7

2

1

3

6129 M

1 hour

0

2

Ne

4

24 hours*

 

6130 M#

1 hour

1

3

1

3

24 hours

1

3

1

3

48 hours

2

3

1

3

72 hours

3

3

2

3

Day 7

3

2

2

3

Day 14

1

1

+

3

Day 21

0

1

0

3

Mean (24, 48 and 72 hours)

2

3

1.3

3

6131 M#

1 hour

1

3

+

2

24 hours

2

3

1

2

48 hours

3

2

1

1

72 hours

3

2

1

1

Day 7

3

1

0

+

Day 14

0

0

0

0

Mean (24, 48 and 72 hours)

2. 7

2.3

1

1.3

6103 M#

1 hour

1

3

+

1

24 hours

2

3

1

1

48 hours

3

2

1

1

72 hours

3

3

1

1

Day 7

3

2

+

2

Day 14

2

1

+

2

Day 21

1

1

+

2

Mean (24, 48 and 72 hours)

2.7

2. 7

1

1

* Animals found dead

# Eyes washed 20 sec post-instillation

Ne: Not evaluated due to severity of response; score considered to be maximum (2) for calculation of mean value

NC: Not evaluated due to necrosis in conjunctiva, score considered to be maximum (3) for calculation of mean value

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, arsenic acid is classified as ‘R41 Risk of serious damage to eyes’ according to the criteria of Annex VI of the Directive 67/548/EEC and ‘Irreversible effects on the eye (Category 1)’ in CLP Regulation (EC) No. 1272/2008.
Executive summary:

In an eye irritation study conducted similarly to the OECD Guideline 405 and in compliance with GLP, 9 (8 males, 1 female) rabbits of the New Zealand White strain were exposed to 0.1 mL of undiluted Desiccant L-10 (arsenic acid) in their right eye while the other eye corresponded to the control. Treated and control eyes of six animals remained unwashed. Twenty seconds after instillation, both eyes of the remaining three animals were rinsed for one minute with lukewarm tap water. The eyes were observed at 1, 24, 48 and 72 hours and 7, 10, 14, 17 and 21 days after instillation and graded according to the method of Draize (1959).

 

All nine animals exhibited moderate to severe conjunctival irritation (redness, chemosis, discharge), conjunctival necrosis, iridial damage and extensive corneal opacity and/or ulceration. Effects were slightly less severe in the washed eyes. 1/3 animal with washed eyes was free of ocular irritation within 14 days post-instillation. Remaining animals continued to exhibit severe irritation (including corneal opacities) at termination of the study (Day 21). All animals with non-washed eyes had severe irritation prior to being found dead or prior to sacrifice for humane reasons on Day 9. Mean individual scores at 24, 48 and 72 h after exposure for animals with unwashed eyes were 3, 3, 4, 4, 3 for cornea score; 1.3, 1, 1.7, 2, 1 for iris score; 1, 1.3, 2.3, 1.3, 1.7 for conjunctivae score and 2, 2, 2.3, 3, 2 for chemosis score. Mean individual scores at 24, 48 and 72 h after exposure for animals with washed eyes were 3, 1.3, 1 for cornea score; 1.3, 1, 1 for iris score; 2, 2.7, 2.7 for conjunctivae score and 3, 2.3, 2.7 for chemosis score.

 

Under the test conditions, arsenic acid is classified as ‘R41 Risk of serious damage to eyes’ according to the criteria of Annex VI of the Directive 67/548/EEC and ‘Irreversible effects on the eye (Category 1)’ in CLP Regulation (EC) No. 1272/2008.

This study is acceptable and satisfies the guideline requirement for an eye irritation study (OECD 405).