Reaction mass of Resin acids and Rosin acids, hydrogenated, potassium salts and potassium [1R-(1α,4aβ,10aα)]-1,2,3,4,4a,9,10,10a-octahydro-7-isopropyl-1,4a-dimethylphenanthren-1-carboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From 6 DEC 2004 to 14 DEC 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD Guideline 405 and GLPs.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Resin acids and Rosin acids, hydrogenated, potassium salts

EC Number:

273-572-4

EC Name:

Resin acids and Rosin acids, hydrogenated, potassium salts

Cas Number:

68990-01-2

Molecular formula:

no data available

IUPAC Name:

Resin acids and Rosin acids,hydrogenated, potassium salts

Details on test material:

-Test material (as cited in report): Resin acids and Rosin acids, hydrogenated, potassium salts
-Batch/Lot number: X29363-079
-Physical state: Solid, tan chunks
-Supplier: Eastman Chemical Company, Kingsport, TN

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS:
-Source: Covance Research Products, Inc., Denver, Pennsylvania, USA
-Sex: not specified
-Age: at least three months old
-Acclimation period: 5 days
-Housing: individually in suspended stainless steel mesh cages
-Diet: Certified High Fiber Rabbit Diet (PMI #5325), ad libitum
-Water: local municipality, ad libitum
-Method of animal identification: uniquely-numbered ear tags and cage cards

ENVIRONMENTAL CONDITIONS:
-Temperature (°C): 20.0-22.7
-Humidity (%): 33.6-61.9
-Photoperiod: 12 hours light/12 hours dark

IN-LIFE DATES:
-Experimental Start Date: 2004-12-06
-Experimental Completion Date: 2004-12-14

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated right eye served as the control for each animal

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

3 rabbits: one eye (left) exposed; the eyes were not irrigated after instillation of the test substance.
3 rabbits: one eye (left) exposed; the eyes were immediately irrigated with distilled water after instillation of the test substance.

Observation period (in vivo):

1, 24, 48, 72 hours and 7 days after instillation of the test substance

Number of animals or in vitro replicates:

6

Details on study design:

Preparation of animals:
Both eyes of each rabbit selected for the study were examined within 24 hours prior to administration of the test substance. Any animal showing eye irritation, ocular defects, or pre-exisiting corneal injury was not used.

Test substance exposure:
A single dose of 0.1 g of the test substance was placed into the conjunctival sac of the left eye. The treated eyes of three rabbits were immediately washed with running distilled water; the eyes of three rabbits were not irrigated.

Clinical Observations:
Eyes were observed immediately after instillation of the test substance and at 1, 24, 48, and 72 hours thereafter. Observations included indications of immediate sensory irritation and estimations of chemosis and redness of the adnexal structures. Also evaluated were effects on the iris, the presence of corneal opacity, and/or discharge from the eye. Eyes were treated with a 2% ophthalmic solution of fluorescein at 24 hours and observed for staining.

Grading the irritant response:
The eyes were examined and grade of ocular reactions recorded for each animal at all observation periods. Grading was conducted according to OECD Guideline 405 (Grading for Ocular Lesions) and is described below:

Grading of Ocular Lesions
Cornea
0 = No ulceration or opacity
1 = Scattered or diffuse areas of opacity (other than slight dulling or normal luster), details of iris clearly visible
2 = Easily discernible translucent area, details of iris slightly obscured
3 = Nacreous area, no details of iris visible, size of pupil barely discernible
4 = Opaque cornea, iris not discernible through the opacity

Area of Corneal Opacity
1 = One-quarter or less, but not zero
2 = Greater than one-quarter up to one-half
3 = Greater than one-half up to three-quarters
4 = Greater than three-quarters up to the whole area

Iris
0 = Normal
1 = Markedly deepened folds, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combinations of any thereof, iris still reacting to light (sluggish reaction is positive)
2 = No reaction to light, hemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness: refers to palpebral and bulbar conjunctivae excluding cornea and iris
0 = Blood vessels normal
1 = Some blood vessels definitely injected
2 = Diffuse crimson red, individual vessels not easily discernible
3 = Diffuse beefy red

Chemosis; lids and/or nictitating membranes
0 = No swelling
1 = Any swelling above normal (including nictitating membranes)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids more than half closed

Body weight determinations:
Animals were not weighed.

Necropsy:
Necropsies were not performed at the conclusion of the test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hours, 7 days

Score:

0

Max. score:

4

Remarks on result:

other: No corneal effects were observed in either washed or unwashed eyes.

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hours, 7 days

Score:

0

Max. score:

2

Remarks on result:

other: No effects on the iris were observed in washed or unwashed eyes.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 hour

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means were calculated for unwashed eyes only: Redness (Grade 1) was noted in 2/3 unwashed eyes; Redness (Grade 2) was noted in 1/3 unwashed eyes. Redness (Grade 1) was observed in all washed eyes.

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means calculated for unwashed eyes only: Redness (Grade 2) noted in 3/3 unwashed eyes at 24, 48 and 72 hours. Redness (Grade 1) observed in 3/3 washed eyes at 24-hr observation and in 2/3 washed eyes at 48 hours. All washed eyes were normal at 72 hours.

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 hour

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means were calculated for unwashed eyes only: No chemosis was observed in washed or unwashed eyes at the 1-hour observation.

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means were calculated for unwashed eyes only: Chemosis (Grade 2) was observed in 3/3 unwashed eyes. No chemosis was observed in washed eyes.

Results 7

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 48 hours

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means calculated for unwashed eyes only: Chemosis (Grade 3) observed in 2/3 and (Grade 1) observed in 1/3. Due to severity of effects in unwashed eyes, eyes were treated with 0.5% tetracaine hydrochloride anesthetic. No chemosis observed in washed eyes.

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72 hours

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Means were calculated for unwashed eyes only: Chemosis (Grade 2) was observed in 2/3 unwashed eyes; the other unwashed eye was normal. No chemosis was observed in washed eyes.

Other effects:

Staining was not evident for unwashed or washed eyes when tested with fluorescein dye 24 hours after administration of the test substance. Irrigation of the treated eyes was palliative.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Resin acids and Rosin acids, hydrogenated, potassium salts was irritating when instilled into the eyes of three New Zealand White rabbits under the conditions used in this study. There were no signs of adverse effects on the cornea or iris at any time during the study. Mean scores for conjunctival redness in unwashed eyes were 2 at the 24-, 48- and 72-hour examinations. Mean scores for chemosis were 2, 2.33 and 1.33 at the 24-, 48-, and 72-hour examinations, respectively. All treated unwashed eyes were normal within 7 days of exposure. Immediate washing was palliative. When the test material was instilled into rabbit eyes followed by immediate flushing of the eyes, there were no adverse effects on the cornea or iris, and there was no evidence of chemosis. Conjunctival redness (Grade 1) in washed eyes was seen only at the 24- and 48-hour examinations. Resin acids and Rosin acids, hydrogenated, potassium salts is considered to be an eye irritant in rabbits.

Resin acids and Rosin acids, hydrogenated, potassium salts is not classified for Serious Eye Damage/ Eye Irritation in Annex I of Directive 67/548/EEC. Resin acids and Rosin acids, hydrogenated, potassium salts meets the criteria for classification for Serious Eye Damage/Eye Irritation (Category 2B) according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and is classified as Category 2 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Executive summary:

In an acute ocular irritation study, 0.1 g of Resin acids and Rosin acids, hydrogenated, potassium salts was instilled into the conjunctival sac of one eye of each of six New Zealand White rabbits. Immediately after instillation, the eyes of three rabbits were washed with running distilled water and the eyes of the other three rabbits were not irrigated. The eyes were examined at 1, 24, 48, 72 hours, and 7 days post-instillation according to OECD Guideline 405. There were no adverse effects on the cornea or iris in either washed or unwashed eyes. Signs of irritation in unwashed eyes included slight to severe chemosis and slight to moderate redness of the conjunctivae. In washed eyes, signs of irritation were limited to slight redness of the conjunctivae. Irritation was fully reversible in the unwashed eyes by 7 days and in washed eyes by 72 hours. Based on the results of this study, Resin acids and Rosin acids, hydrogenated, potassium salts is considered to be an ocular irritant.