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Toxicological information

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 OECD Guideline 405.
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:
read-across: supporting information
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD Guideline 405.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48, and 72 hours, and 7 days
Score:
0
Max. score:
4
Remarks on result:
other: No irritant effect from the test substance was noted for the cornea during the 7-day observation period.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, and 72 hours, and 7 days
Score:
0
Max. score:
2
Remarks on result:
other: No irritant effect from the test substance was noted for the irises during the 7-day observation period.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: At 24 hours, erythema (Grade 1) was noted for all three treated eyes. Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: At 24, 48, and 72 hours, erythema (Grade 1) was noted for two of three treated eyes. Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Swelling (chemosis) (Grade 2) was noted at 1 hour post-dose for all three treated eyes. The chemosis resolved in all eyes by the 24-hour observation time.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Swelling (chemosis) (Grade 2) had been noted at 1 hour post-dose for all three treated eyes. The chemosis resolved in all eyes by the 24-hour observation time.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
No signs of corneal opacity or iris irritation were seen during the study. Conjunctival redness (Grade 1) was noted for all eyes at the 1-hour examinations and for two of three eyes at the 24-, 48-, and 72-hour examinations. Chemosis (Grade 2) was noted for all eyes but was limited to the 1-hour examinations. Fluorescein staining was not evident for any of the three eyes when tested at the 24-hour examinations.
Other effects:
There were no abnormal systemic signs noted during the observation period.

Mean scores for corneal opacity, iris lesions, conjunctival redness and conjunctival edema (chemosis) were calculated for individual animals at 24, 48, and 72 hours after test substance application. Individual means are provided in the table below.

 

Individual Irritation Scores and Means at 24-, 48- and 72-Hours

ANIMAL TIME (HR) Corneal Opacity Iris Lesions Conjunctival Redness Chemosis
440 24 0 0 1 0
  48 0 0 1 0
  72 0 0 1 0
Individual Mean   0 0 1 0
442 24 0 0 0 0
  48 0 0 0 0
  72 0 0 0 0
Individual Mean   0 0 0 0
443 24 0 0 1 0
  48 0 0 1 0
  72 0 0 1 0
Individual Mean   0 0 1 0
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
The study found that Resin acids and Rosin acids, hydrogenated, Me esters is slightly irritating, but not corrosive to rabbit eyes. There were no signs of corneal opacity or iris lesions in any of the treated animals. Chemosis (Grade 2) was present in all animals at the one hour observation only and conjunctival redness (Grade 1) was present in two of three animals at 24, 48 and 72 hours. The irritant effects were fully reversible in 7 days. None of the three animals tested had an individual mean value of ≥1 for corneal opacity, ≥1 for iritis, ≥2 for conjunctival redness or ≥2 for chemosis from gradings at 24, 48, and 72 hours.

Based on the results of this study, this material was not considered to be irritating to rabbit eyes, and therefore, presents a low irritation hazard upon eye contact under conditions of normal use. Scores were insufficient to classify Resin acids and Rosin acids, hydrogenated Me esters as Category 1 (corrosive) or Category 2 (irritating) to eyes according to 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, hydrogenated, methyl esters 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, young adult New Zealand white rabbits (3 females) were exposed to 0.1 mL of undiluted Resin acids and Rosin acids, hydrogenated, Me esters in one eye. Animals were then observed for 7 days. Ocular reactions were scored according to the scale prepared by Draize (1944) for grading the severity of ocular lesions. The eyes of all rabbits were treated with fluorescein dye at 24 hours and examined. The test material caused minimal eye irritation which was completely reversible in seven days. Based on the results of this study, Resin acids and Rosin acids, hydrogenated, Me esters is not considered to be an eye irritant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The body weight of one of the animals, Animal 440 (2464 g) was slightly below the body weight range as specified in the protocol (2.5 - 3.5 kg).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Identity (according to study report): Hercolyn D-E
-Chemical name (IUPAC): Methyl ester of rosin, partially hydrogenated
-Purity: Not reported
-Batch No.: MTM 0009
-Appearance: Light amber liquid resin
-Specific gravity: 1.02 grams/liter at 25 °C
-Vapor Pressure: < 0.1 mm Hg at 25 °C
-Boiling Point: approximately 360 °C
-Stability: Stable
-Solubility: Soluble in alcohols, ethers, vegetable and mineral oils
-Storage: At ambient temperature in the dark
-Date test material received: March 4, 1986

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
-Source: The Broekman Institute, Someren, Netherlands
-Date received at Testing Laboratory: April 10, 1986
-Animals: 3 females
-Age: young adults (12 to 14 weeks at time of arrival)
-Quarantine period: 7 days followed by 4 days of acclimation
-Weight at Study Initiation: 2464 - 2923 g
-Housing: 1/cage in plastic cages with perforated floors
-Bedding: placed beneath the cages and changed at least 3x/week
-Diet: Feed standard laboratory diet (100 g/day) obtained from Hope Farm, Woerden (LK-01 pellets)
-Water: Tap water ad libitum
-Identification method: uniquely ear marked (No. 440, 442, and 443)
-Method of Animal Distribution: no data

ENVIRONMENTAL CONDITIONS:
-Room temperatur (°C): 20 - 22
-Relative humidity (%): 40 - 80
-Light: 12 hour light/12 hour dark cycle

IN-LIFE DATES:
-Date of experiment initiation: April 21, 1986
-Date of experiment termination: April 28, 1986

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The remaining untreated eye of each rabbit served as a control.
Amount / concentration applied:
0.1 mL for one eye of each rabbit
Duration of treatment / exposure:
single dose
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 females
Details on study design:
-Conducted according to OECD Guidelines for Testing of Chemicals, Guideline No. 405: Acute Eye Irritation/Corrosion, May 12, 1981.

-Test material administration: The test material was administered as received. An amount of 0.1 mL was placed by syringe into the conjunctival sac of the left eye of each rabbit. After instillation, the lids were held together for two seconds to insure adequate distribution of the test material. The right eye remained untreated and served as a control.

-Observations: The treated eye of each rabbit was examined for irritation of the cornea, iris, and conjunctiva at 1, 24, 48, and 72 hours, and 7 days post dose. Ocular reactions were scored according to the scale of weighted scores for grading severity of ocular lesions (Draize, 1944). The eyes of all rabbits were examined with sodium fluorescein at 24 hours. The general health of the rabbits was monitored at each observation time.

-Body weights: recorded pretest

Reference:
Draize et al., 1944. J. Pharmacol. Exp. Ther. 83:377-390.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1, 24, 48, and 72 hours, and 7 days
Score:
0
Max. score:
4
Remarks on result:
other: No irritant effect from the test substance was noted for the cornea during the 7-day observation period.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1, 24, 48, and 72 hours, and 7 days
Score:
0
Max. score:
2
Remarks on result:
other: No irritant effect from the test substance was noted for the irises during the 7-day observation period.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: At 24 hours, erythema (Grade 1) was noted for all three treated eyes. Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: At 24, 48, and 72 hours, erythema (Grade 1) was noted for two of three treated eyes. Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: Redness (erythema) resolved in all eyes by the 7 day observation time.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 hour
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Swelling (chemosis) (Grade 2) was noted at 1 hour post-dose for all three treated eyes. The chemosis resolved in all eyes by the 24-hour observation time.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, and 72 hours and 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Swelling (chemosis) (Grade 2) had been noted at 1 hour post-dose for all three treated eyes. The chemosis resolved in all eyes by the 24-hour observation time.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
No signs of corneal opacity or iris irritation were seen during the study. Conjunctival redness (Grade 1) was noted for all eyes at the 1-hour examinations and for two of three eyes at the 24-, 48-, and 72-hour examinations. Chemosis (Grade 2) was noted for all eyes but was limited to the 1-hour examinations. Fluorescein staining was not evident for any of the three eyes when tested at the 24-hour examinations.
Other effects:
There were no abnormal systemic signs noted during the observation period.

Any other information on results incl. tables

Mean scores for corneal opacity, iris lesions, conjunctival redness and conjunctival edema (chemosis) were calculated for individual animals at 24, 48, and 72 hours after test substance application. Individual means are provided in the table below.

 

Individual Irritation Scores and Means at 24-, 48- and 72-Hours

ANIMAL TIME (HR) Corneal Opacity Iris Lesions Conjunctival Redness Chemosis
440 24 0 0 1 0
  48 0 0 1 0
  72 0 0 1 0
Individual Mean   0 0 1 0
442 24 0 0 0 0
  48 0 0 0 0
  72 0 0 0 0
Individual Mean   0 0 0 0
443 24 0 0 1 0
  48 0 0 1 0
  72 0 0 1 0
Individual Mean   0 0 1 0

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
The study found that Resin acids and Rosin acids, hydrogenated, Me esters is slightly irritating, but not corrosive to rabbit eyes. There were no signs of corneal opacity or iris lesions in any of the treated animals. Chemosis (Grade 2) was present in all animals at the one hour observation only and conjunctival redness (Grade 1) was present in two of three animals at 24, 48 and 72 hours. The irritant effects were fully reversible in 7 days. None of the three animals tested had an individual mean value of ≥1 for corneal opacity, ≥1 for iritis, ≥2 for conjunctival redness or ≥2 for chemosis from gradings at 24, 48, and 72 hours.

Based on the results of this study, this material was not considered to be irritating to rabbit eyes, and therefore, presents a low irritation hazard upon eye contact under conditions of normal use. Scores were insufficient to classify Resin acids and Rosin acids, hydrogenated Me esters as Category 1 (corrosive) or Category 2 (irritating) to eyes according to 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, young adult New Zealand white rabbits (3 females) were exposed to 0.1 mL of undiluted Resin acids and Rosin acids, hydrogenated, Me esters in one eye. Animals were then observed for 7 days. Ocular reactions were scored according to the scale prepared by Draize (1944) for grading the severity of ocular lesions. The eyes of all rabbits were treated with fluorescein dye at 24 hours and examined. The test material caused minimal eye irritation which was completely reversible in seven days. Based on the results of this study, Resin acids and Rosin acids, hydrogenated, Me esters is not considered to be an eye irritant.