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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
Study period:
From 2017-03-12 to 2017-04-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl 2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)benzoate
Cas Number:
304435-84-5
Molecular formula:
C16H24N2O5S
IUPAC Name:
Ethyl 2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)benzoate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Batch No.: APM0005851606003
Purity/Composition: 99.8% w/w
Test item storage: At room temperature

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, Sulzfeld, Germany
- Age at study initiation: approximately 29-35 weeks old
- Weight at study initiation: 3926 to 4316 g
- Housing: housed individually in labeled cages with perforated floors (dimensions 67 x 62 x 55 cm) equipped with water bottles
- Diet: Pelleted diet for rabbits was provided once daily throughout the study. In addition, hay was available during the study period.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C
- Humidity: 58 to 63%
- Air changes: Ten or greater per hour
- Photoperiod: 12-hour light/12-hour dark cycle

IN-LIFE DATES: From: 2017-03-12 To: 2017-04-11

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 99.7 mg (range 99.1 – 100.0 mg)
Duration of treatment / exposure:
14 days
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
In-life Procedures, Observations, and Measurements
Mortality
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.
Clinical Observations
Postdose Observations
Postdose observations were performed once daily throughout the study, the observation period was 14 days.
Body Weights
Animals were weighed individually on Day 1 (predose) and on the day of the final observation.
Irritation
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and 14 days after instillation of the test item. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.56
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.44
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Instillation of test substance resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity and epithelial damage. The corneal injury resolved within 72 hours in one animal and within 7 days in the other two animals.
Iridial irritation was observed and resolved within 48 hours in two animals and within 72 hours in the third animal.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days.
There was no evidence of ocular corrosion.
Other effects:
No staining of (peri) ocular tissues by the test item was observed and no test item remnants were seen.
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Individual Eye Irritation Scores:

Eye reaction

Time after treatment

Individual scores-rabbit number and sex

236 Male

219 Male

221 Male

Cornea opacity

1 hour

24 hours

48 hours

72 hours

0

1

1

0

0

1

1

0

0

1

0

0

Iris

1 hour

24 hours

48 hours

72 hours

0

1

0

0

0

1

1

0

0

1

0

0

Conjunctivae redness

1 hour

24 hours

48 hours

72 hours

2

2

2

2

2

2

2

2

2

2

2

2

Chemosis

1 hour

24 hours

48 hours

72 hours

2

2

1

1

2

2

1

1

2

3

1

1

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
Based on the test results:
• according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), test item should be classified as : irritating to eyes (Category 2A).
• according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), test item should be classified as Irritating to eyes (Category 2) and labeled as H319: Causes serious eye irritation.
Based on the maximum group mean of 27.3, test item should be classified as moderate irritant to the rabbit eye according to the Kay and Calandra classification system.
Executive summary:

The objective of this acute eye irritation study was to assess the possible irritation or corrosion potential when a single dose of test item was placed in the conjunctival sac of the rabbit eye according to OECD No.405 (2012) and EC No 440/2008, part B.

Single samples of approximately 99.7 mg of test item (a volume of approximately 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 and 14 days after instillation.

Instillation of the test item resulted in effects on the cornea, iris and conjunctivae. The corneal injury consisted of opacity and epithelial damage. The corneal injury resolved within 72 hours in one animal and within 7 days in the other two animals. Iridial irritation was observed and resolved within 48 hours in two animals and within 72 hours in the third animal.

The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days.

Based on the test results:

• according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), test item should be classified as : irritating to eyes (Category 2A).

• according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), test item should be classified as Irritating to eyes (Category 2) and labeled as H319: Causes serious eye irritation.

Based on the maximum group mean of 27.3, test item should be classified as moderate irritant to the rabbit eye according to the Kay and Calandra classification system.

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