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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-09-23 to 1999-10-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
the European Economic Communities (EEC) Guideline in the Official Journal of the European Communities [92/69, Annex V, B5 (1992)l
Deviations:
no
Qualifier:
according to
Guideline:
other: the Japanese Agricultural Chemicals Laws and Regulations Testing Guidelines for Toxicology Studies published by the Society of Agricultural Chemicals Industry, under the auspices of the (MAFF) [59 NohSan No. 4200 (1985)
Deviations:
no
GLP compliance:
yes
Remarks:
in compliance with the United States Environmental Protection Agency (EPA) Good Laboratory Practice Regulations (40 CFR Parts 160 and 792)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Substance type: benzenesulphonate
- Physical state: dark brown, viscous liquid
- Analytical purity: Test article purity data are the responsibility of sponsor
- Impurities (identity and concentrations): not provided
- Composition of test material, percentage of components: UVCB
- Lot/batch No.: None provided
- Stability under test conditions: Test article stability data are the responsibility of the sponsor
- Storage condition of test material: Ambient
- Date received: April 28,1999

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, PA
- Age at study initiation: Young adult
- Weight at study initiation: 3295 to 3615 grams at initiation of dosing
- Housing: Individually in suspended wire mesh cages
- Diet: PMI Nutrition International, Inc. Certified Rabbit LabDiet@ 5322 was offered at approximately 150 g per day during the study.
- Water (e.g. ad libitum): Municipal water was provided ad libitum.
- Acclimation period: for a minimum of seven days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): (68.2 - 69.1°F; 20 - 21 °C)
- Humidity (%): 30.2-64.1
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
Prior to use, the original container of the test article was agitated to insure a homogeneous mixture. A sufficient amount of test article was dispensed into a labeled storage container and a stir bar was added. The test article was stirred continuously throughout use.
The test article was placed directly into the cupped lower conjunctival sac of each rabbit's right (test) eye. The eyelids were held closed for approximately one second after instillation. Left eyes were manipulated in an identical manner to simulate the dosing of the right eyes.
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single, unwashed exposure.
Observation period (in vivo):
at approximately one, 24, 48 and 72 hours after dosing and on days 4, 7, 14 and 21, if irritation persisted.
Number of animals or in vitro replicates:
6 (Two males and four females)
Details on study design:
REMOVAL OF TEST SUBSTANCE: Washing: no
SCORING SYSTEM: presented in "Any other information on materials and methods incl. tables".
TOOL USED TO ASSESS SCORE: fluorescein, ophtalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24, 48 and 72 hour
Score:
12.2
Max. score:
110
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: at one-hour post-instillation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: no findings
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: no findings
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72-h readings
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72-h readings
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72-h readings
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
other: mean of 24, 48 and 72-h readings
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #5
Time point:
other: mean of 24, 48 and 72-h readings
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72-h readings
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72-h readings
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72-h readings
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72-h readings
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: mean of 24, 48 and 72-h readings
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: mean of 24, 48 and 72-h readings
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: mean of 24, 48 and 72-h readings
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
No animals vocalized upon instillation of the test article. All animals were noted with conjunctival irritation. Iridal irritation was noted for one animal. There were no corneal findings. All irritation completely subsided by day 21. The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study.
Other effects:
There were no deaths or remarkable body weight changes during the study period.

Any other information on results incl. tables

Table 1. Individual ocular irritation scores

 

 

 

Examination intervals

 

Animal

Sex

Tissue

1h

24h

48h

72h*

4 days

7 days*

14 days*

21 days*

Mean (24-48-72 h)

29139

M

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

0-0

0-0

-

0.0

 

 

Iris

1

0

0

0

0

0

0

-

0.0

 

 

Conjunctiva (R-C-D)

2-2- 2

2-1-2

2-1-0

2-0-0

2-0-0

2-0-0

0-0-0

-

2.0 (R) - 0.7 (C)

29143

M

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

0-0

0-0

0-0

0.0

 

 

Iris

0

0

0

0

0

0

0

0

0.0

 

 

Conjunctiva (R-C-D)

2-2-2

2-2-0

2-1-0

2-0-0

2-0-0

2-0-0

1-0-0

0-0-0

2.0 (R) – 1.0 (C)

29158

M

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

-

-

-

0.0

 

 

Iris

0

0

0

0

0

-

-

-

0.0

 

 

Conjunctiva (R-C-D)

2-1-1

2-1-0

2-1-0

1-0-0

0-0-0

-

-

-

1.7 (R) - 0.7 (C)

29148

F

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

0-0

0-0

-

0.0

 

 

Iris

0

0

0

0

0

0

0

-

0.0

 

 

Conjunctiva (R-C-D)

2-2-2

2-2-0

2-0-0

2-0-0

2-0-0

1-0-0

0-0-0

-

2.0 (R) - 0.7 (C)

29155

F

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

0-0

-

-

0.0

 

 

Iris

0

0

0

0

0

0

-

-

0.0

 

 

Conjunctiva (R-C-D)

2-2-2

2-2-0

2-1-0

2-0-0

2-0-0

0-0-0

-

-

2.0 (R) – 1.0 (C)

29156

F

Cornea (O-A)

0-0

0-0

0-0

0-0

0-0

0-0

0-0

-

0.0

 

 

Iris

0

0

0

0

0

0

0

-

0.0

 

 

Conjunctiva (R-C-D)

2-2-2

2-2-0

2-1-0

2-0-0

2-0-0

1-0-0

0-0-0

-

2.0 (R) – 1.0 (C)

Total

 

 

73

44

34

22

20

12

2.0

0.0

 

Mean

 

 

12.2

7.3

5.7

3.7

3.3

2.0

0.3

0.0

 

Mean group scores

 

Cornea

 

 

 

 

 

 

 

 

0.0

 

 

Iris

 

 

 

 

 

 

 

 

0.0

 

 

Conjunctiva

 

 

 

 

 

 

 

 

2.0 (R) – 0.9 (C)

*Sodium fluorescein in solution applied;

O = opacity;
A = area;

R = redness;

C = chemosis;

D = discharge;

h = hours;

M = male;

F = female

- = no observation made anymore 

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the classification criteria outlined in the section 3.3.2.3.2.2. (Guidance on the Application of CLP criteria, 2013), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctival oedema (chemosis) (score ≥ 2) in at least 4 of 6 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned. The average irritation scores over 24, 48, and 72 hours for both corneal opacity and iritis were 0.0 in each of six animals. The mean conjunctival chemosis scores (swelling) for each animal were all under the cut-off value of 2.0 for this time period. However, the positive responses (score of 2.0) were observed in 5 of 6 animals regarding conjunctival erythema (redness). The irritation reactions were completely reversible within 21 days. Based on this observation, the target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts) is classified as Eye Irritant (Category 2, H319) according to Regulation (EC) No. 1272/2008.
Executive summary:

The primary ocular irritation potential of C20 -24 sodium sulfonate (TBN=448) was evaluated in this study with New Zealand White rabbits. There was one group of six albino rabbits that received a single, unwashed exposure. Each 0.1 mL dose of the test article was instilled into the lower conjunctival sac of the right eye. The eyelid was held closed for approximately one second and released. The left eye was manipulated in a similar manner as the right eye and served as a contralateral control. The eyes were examined for ocular reactions in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing and on days 4, 7, 14 and 21, if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours and on days 7, 14 and 21. There were no deaths or remarkable body weight changes during the study period. All animals were noted with positive (grade 2) conjunctival irritation. Iridal irritation was noted for one animal. There were no corneal findings. All irritation completely subsided by day 21. The Maximum Average Score for C20 -24 sodium sulfonate (TBN=448) was 12.2 at one-hour post-instillation.

The following table presents the mean scores calculated from individual scores:

Conjunctiva

-      Redness

-      Oedema

24 and 72 hours

24,48 and 72 hours

1.9

2.0

0.8

0.9

Iris

0.0

0.0

Cornea

0.0

0.0