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:
04 May 2010 to 08 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate
EC Number:
700-204-6
Cas Number:
1174627-68-9
Molecular formula:
C9H17NO3
IUPAC Name:
methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): DV-SOLV 1059

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K LAP Kft, 2173 Kartal, Csaszard ut 135, Hungary
- Age at study initiation:approx, 15 weeks
- Weight at study initiation: 3784-4615 g
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 33 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 24-62
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 03-Feb-2010 To: 22-Mar-2010

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL/animal
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
2 weeks
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
Washing (if done): no washing done


SCORING SYSTEM: according to the numerical scoring system listed in the Commission Regulation (EC) No 440/2008, B.5.
Data were summarized in tabular form, showing for each individual animal the irritation scores for the designated observation time, a description of the degree and nature of irritation, the presence of serious lesions and non-ocular effects. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values (with the exception of the sclerae) for each type of lesion.


TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: individual mean scores: 1.0; 1.0; 1.0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72hours after instillation
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: individual mean scores: 0.67; 0.33; 0.00
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
2.45
Max. score:
3
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: individual mean scores: 3.00; 2.67; 1.67
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: individual mean scores: 0.33; 1.33; 0.67
Irritation parameter:
other: conjunctival discharge
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
2.22
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: individual mean scores: 2.33, 2.33, 2.00
Irritant / corrosive response data:
The test item induced significant irritation but no irreversible damage to the rabbit eye.
Other effects:
None

Any other information on results incl. tables

Individual Scores of eye irritation

 

Abbreviations:

R:     Redness CH:      Chemosis         D:        Discharge         OD:     Opacity degree of density

OE:   Extension of opaque area IPR:     Initial pain reaction        -:         No data

 

Time

Animal No.

Score of Irritation

IPR

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 hour

00532

2

3

3

1

4

0

0

-

2

00530

2

3

3

1

4

0

0

-

2

00533

2

3

3

0

0

0

0

-

2

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

24 hours

00532

3

1

3

1

4

0

0

-

00530

3

2

3

1

4

0

0

-

00533

2

2

2

1

4

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

48 hours

00532

3

0

3

1

3

1

0

-

00530

3

2

3

1

4

1

0

-

00533

2

0

3

1

3

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

72 hours

00532

3

0

1

1

2

1

0

-

00530

2

0

1

1

4

0

0

-

00533

1

0

1

1

1

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 week

00532

1

0

0

0

0

0

0

-

00530

1

0

0

1

2

0

0

-

00533

0

0

0

0

0

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

2 weeks

00532

0

0

0

0

0

0

0

-

00530

0

0

0

0

0

0

0

-

00533

0

0

0

0

0

0

0

-

 

Mean values of ocular irritation (24, 48, 72 hour readings)

 

Animal number

Sex

Corneal opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

00532

M

1.00

0.67

3.00

0.33

2.33

00530

M

1.00

0.33

2.67

1.33

2.33

00533

M

1.00

0.00

1.67

0.67

2.00

 

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and
amending Regulation (EC) No 1907/2006), DV-SOLV 1059 is considered to be “irritating” to the rabbit eye.
Executive summary:

An acute eye irritation study of the test item DV-SOLV 1059 was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002). The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A volume of 0.1 mL of the test item was administered as a single dose. The eyes were examined at 1, 24, 48, 72 hours and 1 and 2 weeks after the application.

Initial Pain Reaction() (score 2) was observed in all animals.

One hour after the application, conjunctival redness (score 2) was observed in all animals, conjunctival chemosis (score 3) was noted in all animals, conjunctival discharge (score 3) was seen in all animals and corneal opacity (score 1, extension 4) was observed in two animals.

At 24 hours after treatment,conjunctival redness (score 3) was observed in two animals, conjunctival redness (score 2) in one animal, conjunctival chemosis (score 1) was observed in one animal, conjunctival chemosis (score 2) was seen in two animals, conjunctival discharge (score 3) was noted in two animals, conjunctival discharge (score 2) in one animal and corneal opacity (score 1, extension 4) was seen in all animals.

At 48 hours after treatmentconjunctival redness (score 3) was observed in two animals, conjunctival redness (score 2) was seen in one animal, conjunctival chemosis (score 2) was seen in one animal, conjunctival discharge (score 3) was observed in all animals, corneal opacity (score 1, extension 4) was noted in one animal and corneal opacity (score 1, extension 3) was observed in two animals. The iris was injected (score 1) in two animals.

At 72 hours after treatmentconjunctival redness (score 3) was observed in one animal, redness (score 2) was noted in one rabbit, redness (score 1) was seen one animal, conjunctival discharge (score 1) was found in all rabbits, corneal opacity (score 1, extension 4) was observed in one animal, corneal opacity (score 1, extension 2) was noted in one rabbit and corneal opacity (score 1, extension 1) was seen one rabbit. The iris was injected (score 1) in one animal.

At 1 week after treatmentconjunctival redness (score 1) was found in two animals and corneal opacity (score 1, extension 2) was observed in one rabbit.

At 2 weeks after treatmentthere were no clinical signs observed. As there were no clinical signs observed, the study was terminated. During the study, the control eye of each animal was symptom-free. The general state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the study period.

The test item DV-SOLV 1059, applied to the rabbits eye mucosa, caused significant conjunctival irritant effects at one hour which were not reduced at 48 hours after application. The effects were full reversible within 2 weeks. According to Regulation (EC) No 1272/2008, DV-SOLV 1059 requires classification as an eye irritant(Category 2; Reversible effects on the eye/irritating to eyes).