Registration Dossier

Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted under GLP application, and it was done according to valid methods. Therefore it is considered relevant, reliable and adequate for classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chloroacetamide
EC Number:
201-174-2
EC Name:
2-chloroacetamide
Cas Number:
79-07-2
Molecular formula:
C2H4ClNO
IUPAC Name:
2-chloroacetamide
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Chloracetamid; Diamoll C; Chloressigsäureamid
- Physical state: White, crystalline powder
- Analytical purity: 99.5%
- Purity test date: 1993-04-05
- Lot/batch No.: 676
- Expiration date of the lot/batch: August 1993
- Stability under test conditions: Stability under storage conditions is guaranteed until August 1993
- Storage condition of test material: In the dark at room temperature in a fume cupboard

Test animals / tissue source

Species:
rabbit
Strain:
other: Albino, Chbb: New Zealand White (SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chemisch pharmazeutische Fabrik Dr. Karl Thomae GmbH, Biberach (Germany), SPF-Breeding
- Age at study initiation: Ca. 3 - 5 months
- Weight at study initiation: 2.9-3.4 kg
- Housing: Individual (battery cages)
- Diet: Altromin 2123 Haltungsdiät – Kaninchen by Altromin-GmbH, Lage/Lippe (Germany), ad libitum, also hay, ca. 15 g daily
- Water: Deionised chlorinated water, automatic watering, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%):55 ± 20 %;
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1993-07-27 To: 1993-08-19

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg per eye (left eye only, right eye used as control)
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes with discharges or assessed with fluorescein-sodium solution were rinsed with physiological saline before each assessment.

SCORING SYSTEM: See under 'Any other information on material and methods incl. tables '

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1.7
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
no. 93
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1.7
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
no. 96
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
no. 98
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
2.3
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
no. 93
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
no. 96
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
no. 98
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
1
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
2.9
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
animal #1
Remarks:
no. 93
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
2.7
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
animal #2
Remarks:
no. 96
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
animal #3
Remarks:
no. 98
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
, chemosis
Basis:
mean
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
3
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
, chemosis
Basis:
animal #1
Remarks:
no. 93
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
3
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
, chemosis
Basis:
animal #2
Remarks:
no. 96
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
2.7
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
, chemosis
Basis:
animal #3
Remarks:
no. 98
Time point:
other: mean, 24, 48, 72 h p.appl.
Score:
3.3
Max. score:
4
Irritant / corrosive response data:
1 Hour until 7 days after application the conjunctivae of the animals showed a significant hyperemia of some blood vessels up to a diffuse deep red color and a slight swelling to a swelling with lids more than half-closed. The iris was partially reddened. The cornea showed partially diffuse up to pearlescent areas of opacity . 14 Days after application in one animal there was still a marked hyperemia of some conjunctival blood vessels. The iris of this animals was reddened and the cornea still showed light visible translucent opacity areas. The irritation symptoms were accompanied with clear, colorless or white slimy discharge. Furthermore partially bleeding from the conjunctiva and nictitating membrane were observed. 21 Days after application all signs of irritation were reversible.

Based on the individual scores at 24, 48 and 72 hours the following mean values were calculated:

Corneal opacity Iris score
All animals: 1.7 All animals: 1.0
Animal 93: 1.7 Animal 93: 1.0
Animal 96: 1.0 Animal 96: 1.0
Animal 98: 2.3 Animal 98: 1.0
Conjunctiva redness Conjunctiva chemosis
All animals: 2.9 All animals: 3.0
Animal 93: 2.7 Animal 93: 3.0
Animal 96: 3.0 Animal 96: 2.7
Animal 98: 3.0 Animal 98: 3.3

Any other information on results incl. tables

Table 1. Individual readings

Animal Number

Elapsed Time

Cornea

Iris

Conjunctiva

Opacity

Area

Redness

Chemosis

Discharge

93

1 hour

1

4

1

2

2

2

 

1 day

2

2

1

3

4

3

 

2 days

2

2

1

3

3

2

 

3 days

1

1

1

2

2

1

 

7 days

0

0

0

1

1

0

 

14 days

0

0

0

0

0

0

96

0.9 hours

1

1

0

2

2

1

 

1 day

1

2

1

3

3

2

 

2 days

1

1

1

3

3

1

 

3 days

1

1

1

3

2

1

 

7 days

0

0

0

1

1

0

 

14 days

0

0

0

0

0

0

 

21 days

0

0

0

0

0

0

98

0.9 hours

1

1

0

2

2

2

 

1 day

2

3

1

3

4

3

 

2 days

2

3

1

3

3

2

 

3 days

3

3

1

3

3

2

 

7 days

3

3

1

2

2

0

 

14 days

2

1

1

1

0

0

 

21 days

0

0

0

0

0

0

 

Applicant's summary and conclusion

Interpretation of results:
other: Category 2
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Classification: irritating
Executive summary:

In 3 rabbits, 100 mg chloroacetamide was applied in the conjunctival sac of the left eye. The untreated eye served as control. The assessments of the eyes were made at 1, 24, 48 and 72 hours after application of test substance. At the evaluation time points 24 and 72 hours after application the cornea was additionally examined for damage after instillation of fluorescein-sodium solution. Mean scores for cornea, iris, conjunctival redness and chemosis were 1.7, 1.0, 2.9 and 3.0, respectively. As there were still effects on the eyes at 72 hours, an additional observation was done at 7, 14 and 21 days.

After 21 days all symptoms of irritation were reversible. Based on this study Chloroacetamide was evaluated as irritant.

Categories Display