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Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted methods for an eye irritation study.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted methods for an eye irritation study.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and Day 4 and Day 7
Score:
0
Max. score:
80
Remarks on result:
other: For the 6 unwashed eyes, no irritant effect from the test substance was noted for the cornea during the 7-day observation period. Cornea scores = Opacity Grade x Area Involved x 5
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and Day 4 and Day 7
Score:
0
Max. score:
10
Remarks on result:
other: For the 6 unwashed eyes, no irritant effect from the test substance was noted for the iris during the 7-day observation period. Iris scores = Iris Grade x 5
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48 h
Score:
0.67
Max. score:
20
Remarks on result:
other: For 2/6 unwashed eyes, redness (Grade 1) of the conjunctivae was noted. No other signs of redness were noted for the remaining 4 unwashed eyes during these two examination periods. No signs of discharge or chemosis were evident for the 6 unwashed eyes.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0.33
Max. score:
20
Remarks on result:
other: For 1/6 unwashed eyes, redness (Grade 1) of the conjunctivae was noted. No other signs of redness were noted for the remaining 5 unwashed eyes during this examination period. No signs of discharge or chemosis were evident for the 6 unwashed eyes.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 4 and 7 days
Score:
0
Max. score:
20
Remarks on result:
other: No irritant effect from the test substance was noted for the conjunctivae during the 4- and 7-day examinations. Conjunctiva scores = Redness Grade + Chemosis Grade + Discharge Grade x 2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritant / corrosive response data:
No signs of corneal opacity, iris irritation, discharge, or chemosis were seen during the study. Redness (Grade 1) was noted for 2 of the 6 unwashed eyes at the 24- and 48-hour examinations and for 1 of the 6 unwashed eyes at the 72-hour examinations. Complete reversibility of the irritant effects was seen at the Day 4 examinations.
Other effects:
For the 3 washed eyes, no signs of irritation were present during the 7-day observation period. Irrigation of the eyes was palliative. There were no abnormal systemic signs noted during the observation period and all animals gained weight normally.

Conjunctiva scores = Redness Grade + Chemosis Grade + Discharge Grade x 2 (Maximum grade possible = 20).

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) was, at most, slightly irritating when instilled into the eyes of New Zealand albino rabbits. There was no evidence of adverse effects on the cornea or iris. Signs of irritation were limited to slight redness of the conjunctivae in 2 of 6 unwashed eyes. One eye was normal by the 72-hour observation and the other eye was normal by Day 4. .

Based on the minimal eye irritation scores obtained in this study, PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) is not classifiable for eye irritation according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

This data is being read across from the source study that tested Resin acids and Rosin acids, esters with pentaerythritol based on category read across that is explained in the category justification document attached in Section 13 of the dossier.

In a primary eye irritation study, 100 mg of undiluted PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) was instilled into the conjunctival sac of one eye of each of 9 New Zealand White rabbits (6 eyes were unwashed and 3 were washed). Animals were then observed for 7 days. Ocular reactions were scored at 24, 48, and 72 hours, and 4 and 7 days according to the Draize scale of weighted scores. For the 6 unwashed eyes, no signs of corneal opacity, iris irritation, discharge, or chemosis were seen during the study. Redness (Grade 1) was noted for 2 of the 6 unwashed eyes at the 24- and 48-hour examinations and for 1 of the 6 unwashed eyes at the 72-hour examinations. Complete reversibility of the irritant effects was seen at the Day 4 examinations. For the 3 washed eyes, no signs of eye irritation were noted during the study. Irrigation of the eyes was palliative. There were no abnormal systemic signs noted during the observation period for washed or unwashed eyes. Based on the results of this study, PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) is considered to be, at most, a slight ocular irritant in this study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Resin acids and Rosin acids, polymerized, esters with glycerol
Cas Number:
68475-37-6
Molecular formula:
Not applicable as the substance is a UVCB.
IUPAC Name:
Resin acids and Rosin acids, polymerized, esters with glycerol
Details on test material:
-Name (according to study report): PC 12-99
-Physical state: amber resin
-Date of receipt: 1982-01-15
-pH of the test substance: 5.39
-Purity: No data (responsibility of Sponsor)
-Sample storage: No data

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
-Source: Perfection Breeders, Inc., Douglassville, Pennsylvania, USA
-Animals: 9 (3 eyes washed and 6 eyes unwashed)
-Sex: male and female
-Acclimation period: 5 days
-Weight at study initiation: 2-3 kg
-Housing: Individually in cages
-Diet: Wayne Rabbit Ration available ad libitum
-Water: fresh tap water (drinking water) available ad libitum
-Identification method: each animal was ear tagged and animal cages marked with group number and dose level
-Method of Randomization: selection based upon body weight
-Cage sanitization: Waste material was removed daily. Cages and feeders were sanitized every 2 weeks.

ENVIRONMENTAL CONDITIONS:
-Room temperature (°C): maintained at 20 +/- 3
-Relative humidity (%): maintained at 30-70
-Light: 12 hour light/dark cycle

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The remaining untreated eye of each rabbit served as a control.
Amount / concentration applied:
100 mg applied to one eye of each rabbit
Duration of treatment / exposure:
single dose
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
9
Details on study design:
Twenty-four hours prior to administration of the test substance, both eyes of each rabbit were examined using 2% fluorescein stain. Prior to installation of the test substance, the eyes were re-examined. The test substance was placed into the right eye of 9 animals by gently pulling the lower lid away from the eyeball to form a cup. After installation, the upper and lower lids were gently held together for one second to prevent loss of the material. The treated eyes of 3 rabbits were rinsed for one minute with lukewarm water immediately following administration of the test material. The contralateral eye of the 9 rabbits remained untreated and served as a control. Eyes were examined at 24, 48, and 72 hours, and 4 and 7 days following treatment. The grades of ocular reaction were recorded at each examination using the grading system for irritation according to the method of Draize et al. (1944). The maximum possible scores for eye irritation reactions (excluding necrosis) in this system are: cornea, 80; iris, 10 and conjunctivae, 20. Body weights were recorded on Days -1, 1, and 7.

Reference:
Draize JH, Woodward G, and Calvery HO (1944). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharmacol. Exp. Ther. 82, 377–390.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and Day 4 and Day 7
Score:
0
Max. score:
80
Remarks on result:
other: For the 6 unwashed eyes, no irritant effect from the test substance was noted for the cornea during the 7-day observation period. Cornea scores = Opacity Grade x Area Involved x 5
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and Day 4 and Day 7
Score:
0
Max. score:
10
Remarks on result:
other: For the 6 unwashed eyes, no irritant effect from the test substance was noted for the iris during the 7-day observation period. Iris scores = Iris Grade x 5
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48 h
Score:
0.67
Max. score:
20
Remarks on result:
other: For 2/6 unwashed eyes, redness (Grade 1) of the conjunctivae was noted. No other signs of redness were noted for the remaining 4 unwashed eyes during these two examination periods. No signs of discharge or chemosis were evident for the 6 unwashed eyes.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0.33
Max. score:
20
Remarks on result:
other: For 1/6 unwashed eyes, redness (Grade 1) of the conjunctivae was noted. No other signs of redness were noted for the remaining 5 unwashed eyes during this examination period. No signs of discharge or chemosis were evident for the 6 unwashed eyes.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 4 and 7 days
Score:
0
Max. score:
20
Remarks on result:
other: No irritant effect from the test substance was noted for the conjunctivae during the 4- and 7-day examinations. Conjunctiva scores = Redness Grade + Chemosis Grade + Discharge Grade x 2
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: Individual animal scores not provided; only mean scores available
Irritant / corrosive response data:
No signs of corneal opacity, iris irritation, discharge, or chemosis were seen during the study. Redness (Grade 1) was noted for 2 of the 6 unwashed eyes at the 24- and 48-hour examinations and for 1 of the 6 unwashed eyes at the 72-hour examinations. Complete reversibility of the irritant effects was seen at the Day 4 examinations.
Other effects:
For the 3 washed eyes, no signs of irritation were present during the 7-day observation period. Irrigation of the eyes was palliative. There were no abnormal systemic signs noted during the observation period and all animals gained weight normally.

Any other information on results incl. tables

Conjunctiva scores = Redness Grade + Chemosis Grade + Discharge Grade x 2 (Maximum grade possible = 20).

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) was, at most, slightly irritating when instilled into the eyes of New Zealand albino rabbits. There was no evidence of adverse effects on the cornea or iris. Signs of irritation were limited to slight redness of the conjunctivae in 2 of 6 unwashed eyes. One eye was normal by the 72-hour observation and the other eye was normal by Day 4. .

Based on the minimal eye irritation scores obtained in this study, PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) is not classifiable for eye irritation according to Directive 67/548/EEC, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

In a primary eye irritation study, 100 mg of undiluted PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) was instilled into the conjunctival sac of one eye of each of 9 New Zealand White rabbits (6 eyes were unwashed and 3 were washed). Animals were then observed for 7 days. Ocular reactions were scored at 24, 48, and 72 hours, and 4 and 7 days according to the Draize scale of weighted scores. For the 6 unwashed eyes, no signs of corneal opacity, iris irritation, discharge, or chemosis were seen during the study. Redness (Grade 1) was noted for 2 of the 6 unwashed eyes at the 24- and 48-hour examinations and for 1 of the 6 unwashed eyes at the 72-hour examinations. Complete reversibility of the irritant effects was seen at the Day 4 examinations. For the 3 washed eyes, no signs of eye irritation were noted during the study. Irrigation of the eyes was palliative. There were no abnormal systemic signs noted during the observation period for washed or unwashed eyes. Based on the results of this study, PC 12-99 (Resin acids and Rosin acids, esters with pentaerythritol) is considered to be, at most, a slight ocular irritant in this study.