Registration Dossier

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:
4 April 2003 to 7 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully Guideline- and GLP-compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Resin 835 A (Lot:0161852)
- Molecular formula (if other than submission substance): main component C20H28O2
- Molecular weight (if other than submission substance): main component 300 g/mol
- Physical state: solid melt
- Composition of test material, percentage (w/w) of components: 56 % dehydroabietic acid, 20 % dihydroabietic acid, 9.8 % neutral components, 9 % non ident. rosin acids, 4 % Pimaric acids
- Purity test date: 11 March 2003
- Lot/batch No.: 0161852
- Expiration date of the lot/batch: 17 June 2003
- Storage condition of test material: at approx. 20 °C in a fume cupboard

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kisslegg, Germany
- Weight at study initiation: 2.9 to 3.05 kg
- Housing: no data
- Diet (e.g. ad libitum): ssniff K-H (V2333) ad lib. and hay (approx. 15 g daily)
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 50 +/- 20 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 8 April 2003 To: 6 May 2003

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g
Duration of treatment / exposure:
24 h
Observation period (in vivo):
up to 7 days p.a.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 h after administration the treated eyes were wahsed out thoroughly with isotonic saline at approx. 37 °C- The eyes were also washed out at designated examination times at whoch discharge was observed or a corneal examination with fluorescin was performed.

EYE EXAMINATION
The eyes were examined 1, 24, 48 and 72 hours after administration of the test substance. At 24 and 72 hours and after 7 days, the eyes were further examined for corneal lesions under UV light after instillation of one drop of a 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded when apparent. Since effects were still present in the eyes of two animals after 72 hours, further examination were carried out after 7 days.

SCORING SYSTEM:
CORNEA
Opacity : degree of density (reading should be taken from most dense area)
No ulceration or opacity ................................................................................................... 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details
of iris clearly visible ......................................................................................................... 1
Easily discernible translucent area; details of iris slightly obscured ................................ 2
Nacrous area; no details of iris visible; size of pupil barely discernible .......................... 3
Opaque cornea; iris not discernible through the opacity .................................................. 4

Affected area (opacity or stained by fluoresceine test)
0 = no translucence
1 = punctate to 1/4 2 = more than 1/4 to 1/2
3 = more than 1/2 to 3/4 4 = more than 3/4 to 4/4

IRIS
Normal ............................................................................................................................ 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia;
or injection; iris reacting to light (a sluggish reaction is considered to be an effect) ..... 1
Haemorrhage, gross destruction, or no reaction to light................................................. 2
Not assessable................................................................................................................. 9

CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
Normal ............................................................................................................................ 0
Some blood vessels definitely hyperaemic (injected) .................................................... 1
Diffuse, crimson color, individual vessels not easily discernible................................... 2
Diffuse beefy red ............................................................................................................ 3
Not assessable................................................................................................................. 9
Chemosis (refers to lids and/or nictating membranes)
Normal ............................................................................................................................ 0
Some swelling above normal.......................................................................................... 1
Obvious swelling, with partial eversion of lids .............................................................. 2
Swelling, with lids about half closed.............................................................................. 3
Swelling, with lids more than half closed....................................................................... 4
Discharge
No discharge ................................................................................................................... 0
Any amount different from normal (does not include small amounts normally observed in inner canthus) ............ 1
Discharge with moistening of the lids and hairs just adjacent to the lids....................... 2
Discharge with moistening of the lids hairs and considerable area around the eye ....... 3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24, 48 and 72 h p.a.
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24, 48 and 72 h p.a.
Score:
0.11
Max. score:
0.33
Reversibility:
fully reversible within: 48 h p.a.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24, 48 and 72 h p.a.
Score:
1.22
Max. score:
1.67
Reversibility:
fully reversible within: 7 days p.a. latest
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
for all 3 animals
Time point:
other: 24, 48 and 72 h p.a.
Score:
0.22
Max. score:
0.33
Reversibility:
fully reversible within: 48 h p.a.

Any other information on results incl. tables

One hour up to 48 respectively 72 hours after administration the animals showed some definitely injected blood vessels up to diffuse beefy red color. Obvious swellings of the conjunctivae with partial eversion of lids was noted in all animals 1 hour after application. 24 hours after administration two animals showed slight swellings. One animal showed a moderately reddened iris 24 hours after administration. One hour after administration one animal showed serous eye discharge discolored by the compound. The two other animals showed white mucous eye discharge. 7 days after administration all signs of irritation had disappeared.

Individual data:

Animal

Day

 

Opacity Grade

Opacity Area

Iris

Redness

Chemosis

Discharge

No.

No.

Time Slot

 

 

 

 

 

 

163

1

Treatment

 

 

 

 

 

 

 

 

1 hour after treatment

0

0

0

2

3

2

 

2

24 hours after treatment

0

0

0

2

0

0

 

3

48 hours after treatment

0

0

0

1

0

0

 

4

72 hours after treatment

0

0

0

0

0

0

167

1

Treatment

 

 

 

 

 

 

 

 

1 hour after treatment

0

0

0

2

2

2

 

2

24 hours after treatment

0

0

1

3

1

0

 

3

48 hours after treatment

0

0

0

1

0

0

 

4

72 hours after treatment

0

0

0

1

0

0

 

8

7 days after treatment

0

0

0

0

0

0

168

1

Treatment

 

 

 

 

 

 

 

 

1 hour after treatment

0

0

0

2

2

2

 

2

24 hours after treatment

0

0

0

1

1

0

 

3

48 hours after treatment

0

0

0

1

0

0

 

4

72 hours after treatment

0

0

0

1

0

0

 

8

7 days after treatment

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: EU
Conclusions:
Testing of Resin 835 A (Lot: 0161852) for primary eye irritation in the rabbit showed that the substance is not irritating to eyes according to the classification criteria of Directive 2001/59/EC.
Executive summary:

An amount of 100 mg Resin 835 A (Lot: 0161852) was administered once to the conjunctival sac of the left eye of three female New Zealand White rabbits. The treated eyes were washed out 24 hours after the administration of the test substance. The untreated eyes served in each case as a control.

The test substance caused no severe irritating effects in the eyes of the animals.

Based on the system of evaluation defined by the EC, the following group mean scores for ocular lesions after 24, 48 and 72 hours were calculated:

Redness of conjunctiva : 1.22

Opacity of cornea : 0.0

Chemosis of conjunctiva : 0.22

Iris : 0.11

No clinical signs of systemic toxicity were observed.

Summarizing, testing for primary eye irritation in the rabbit showed that Resin 835 A (Lot: 0161852) is not irritating to eyes according to the classification criteria of Directive 2001/59/EC.