Registration Dossier

Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-chlorophthalic anhydride
EC Number:
204-179-8
EC Name:
3-chlorophthalic anhydride
Cas Number:
117-21-5
Molecular formula:
C8H3ClO3
IUPAC Name:
4-chloro-1,3-dihydro-2-benzofuran-1,3-dione

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male and female New Zealand White rabbits, at least 10 weeks of age, weighing 2.01 to 2.46 kg were obtained from Millbrook Breeding Labs. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages with hardwood chip bedding. They were provided food and tap water ad libitum. Room temperature was 68 ± 5°F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Approximately 24 hours prior to dosing, the eyes of the animals selected for the test were examined to insure that the eyes were free of abnormality, damage and disease. The animals were dosed in the left eye at a volume of 0.1 mL (equivalent to 100 mg).
Duration of treatment / exposure:
The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The eyes were rinsed within two hours of instillation as the test substance was not removed from the eye by physiological mechanisms.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours according to the definitions provided below. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start and on Days 6 and 17, when applicable.
Number of animals or in vitro replicates:
3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
2.2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal: #1, #2
Remarks:
mean value; not determinable in animal 3 due to discharge
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: animal #2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2, #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
3.1
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
Moderate corneal involvement was noted at the one hour mark in all three test eyes. At Day 6, this developed into pannus in two test eyes. The findings resolved in one animal by Day 8. Mild iritis was observed in two animals at 24 hours. The iris could not be observed in the third animal at 24 and 48 hours due to profound swelling, but iritis was noted at 72 hours, and continued in this animal through Day 6. Iris involvement persisted in the remaining two animals through the determination of irreversibility. Moderate conjunctival involvement was noted in all three test eyes by the one hour observation point. Involvement persisted through the conclusion of the study. Irreversible change was observed in one animal in the form of conjunctival ulceration/scarring.
Other effects:
All animals gained weight and no systemic signs of toxicity were observed during the course of the study.

Any other information on results incl. tables

·        Rabbit No.

Effects at 1 hour

Effects at 24 hours

FE

Effects at 48 hours

FE

 

Cornea

Iris

Conj

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44207

1

3

0

2*

3

2

3

1

3**

3

2

4

3

3

1

3^

3

2

3

 

44208

2

3

0

2*

3

2

3

1

3*

3

2

2

2

3

0

3^

3

2

2

 

44209

2

4

0

2*

3

2

4@

**

3*

4

2

4@

2

4@

**

3*

4

2

4@

 

 

Rabbit No.

Effects at 72 hours

FE

Effects at Day 4

FE

Effects at Day 5

FE

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44207

3

2

1

3^

3

3

2

3

3

1

3^

3

3

3

3

2

1

2^

3

3

2

 

44208

1

3

0

3*

2

2

2

1

2

1

3*

2

2

1

1

1

1

3*

2

1

1

 

44209

3

4@

1

3*

3

3

4@

3

4@

**

3^

4

3

4@

3

4@

1

3^

4

3

4@

 

 

Rabbit No.

Effects at Day 6

FE

Effects at Day 7

FE

Effects at Day 8

FE

 

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44207

3~

2

1

2

3

3

2

-

-

-

-

-

-

-

-

-

-

-

-

-

-

 

44208

1

1

0

2*

2

1

1

1

1

0

2*

2

0

0

0

0

0

2

2

0

0

 

44209

3~

4@

1

3

4

3

4@

-

-

-

-

-

-

-

-

-

-

-

-

-

-

 

 

Rabbit No.

Effects at Day 9

FE

Effects at Day 10

FE

Effects at Day 11

FE

 

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44208

0

0

0

2**

2

0

0

0

0

0

1**

2

0

0

0

0

0

2**

2

0

0

 

 

Rabbit No.

Effects at Day 12

FE

Effects at Day 13

FE

Effects at Day 14

FE

 

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44208

0

0

0

1

2

0

0

0

0

0

1

2

0

0

0

0

0

1*

2

0

0

 

 

Rabbit No.

Effects at Day 15

FE

Effects at Day 16

FE

Effects at Day 17

FE

 

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

Cornea

Iris

Conj

IS

A

 

O

A

I

R

C

O

A

I

R

C

O

A

I

R

C

 

44208

0

0

0

1*

2

0

0

0

0

0

1

2

0

0

0~~

0

0

1*

2

0

0

 

O: Opacity; A: Area; I: Iritis; Conj: Conjunctivae; R: Redness; C: Chemosis; FE: Fluorescein Exam; IS: Intensity of Staining

* Discharge - clear

** Discharge - thick, white mucous

^ Discharge - red-tinged

~ Irreversible – Pannus

~~ Irreversible – ulceration of conjunctival membrane with scarring

@ Difficult or unable to read due to swelling

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance is considered to be corrosive to the eye.
Executive summary:

Eye irritation was determined in a study performed according to OECD 405 and in compliance with GLP criteria. In this study, 3 New Zealand White rabbits (male and female) were exposed to 0.1 mL (100 mg) of test substance in the left eye. The eyes were rinsed within two hours of instillation as the test substance was not removed from the eye by physiological mechanisms. The eyes were examined at 1, 24, 48 and 72 hours on the basis of effects on the cornea, iris, conjunctivae redness and chemosis. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start and on Days 6 and 17, when applicable. All animals gained weight and no systemic signs of toxicity were observed during the course of the study. The test substance caused irreversible change in the eye in the form of pannus and conjunctival ulceration/scarring and is therefore considered to be corrosive to the ocular tissue.