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Diss Factsheets

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:
18 Jul 2012 to 23 Jul 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2008
Qualifier:
according to guideline
Guideline:
other: Directive 2004/73/EC B.5 (L 152 2004)
Version / remarks:
2004
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide
EC Number:
617-298-9
Cas Number:
82097-50-5
Molecular formula:
C14H16ClN5O5S
IUPAC Name:
2-(2-chloroethoxy)-N-[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)carbamoyl]benzene-1-sulfonamide

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: Male
- Age at study initiation: Approximately 12 weeks
- Weight at study initiation: 3110– 3328 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: UNI diet for rabbits. Ad libitum
- Water: Tap water. Ad libitum
- Acclimatisation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 48 – 73 %
- Air changes: 15-20 air exchanges/hour
- Photoperiod: 12 hours of light/12 hours of dark

IN-LIFE DATES: From: 18 July 2012 To: 23 July 2012

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
The test item was administered as an instillation of a single dose
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
PRE-STUDY EXAMINATION
- The pH of the test material was measured as pH 5.0, permitting the test material to be used in the animal studies.
- The test was performed on 3 male rabbits. Before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect using a hand-held slit-lamp. Only animals free of ocular damage were used. The eyes were not anaesthetised.

APPLICATION
The test material was placed into the conjunctival sac of the left eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for several seconds immediately after treatment, to prevent loss of the test material

OBSERVATION TIME POINTS
Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment. The eyes were further examined using 2% fluorescein solution approximately 24 hours before treatment and then 24, 48 and 72 hours after treatment

SCORING SYSTEM:
The eye irritation scores were evaluated according to the scoring system by Draize (1977). A modified version of the system described by Kay J H and Calandra J C (1962) was used to classify the ocular irritancy potential of the test material. For criteria, see 'Any other information on materials and methods incl. tables'.

TOOL USED TO ASSESS SCORE: fluorescein

OTHER OBSERVATIONS
- Individual body weight was recorded at dosing and at termination.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #2, #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other:
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
An Initial Pain Reaction (IPR) score of 2 was observed in all animals.
Conjunctival redness (score 2) was seen in all rabbits and conjunctival discharge (score 1) was observed in two animals at 1 hour after treatment. Conjunctival discharge had reversed in all animals at the 24 hour observation. Conjunctival redness had reversed at the 72 hours observation.
Fluorescein staining was negative in all animals at any time point.
As all signs of eye irritation had fully reversed, the study was terminated after a period of 72 hours observation.
Other effects:
- The body weights of all rabbits were considered to be within the normal range of variability.
- No clinical signs of systemic toxicity were observed in any animals in this study.
- No mortality occurred in this study.

Any other information on results incl. tables

Table 3. Individual Draize Scores and Individual Total Scores* for Ocular Irritation


 


















































































































































Rabbit number and sex



 



Male #1



 



Male #2



Male #3



 



 



IPR = 2



 



 



IPR = 2



 



 



IPR = 2



 



Time after treatment



1


Hr



24


Hr



48


Hr



72


Hr



1


Hr



24


Hr



48


Hr



72


Hr



1


Hr



24


Hr



48


Hr



72


Hr



CORNEA


E = Degree of Opacity


F = Area of Cornea


involved



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



 


0


 


0



* Score (E x F) x 5



0



0



0



0



0



0



0



0



0



0



0



0



IRIS


D = Values



 


0



 


0



 


0



 


0



 


0



 


0



 


0



 


0



 


0



 


0



 


0



 


0



* Score (D x 5)



0



0



0



0



0



0



0



0



0



0



0



0



CONJUNCTIVAE


A = Redness


B = Chemosis C = Discharge



 


2


0


0



 


1


0


0



 


0


0


0



 


0


0


0



 


2


0


1



 


1


0


0



 


1


0


0



 


0


0


0



 


2


0


1



 


1


0


0



 


1


0


0



 


0


0


0



* Score (A+B+C) x 2



4



2



0



0



6



2



2



0



6



2



2



0



* Total Score



4



2



0



0



6



2



2



0



6



2



2



0



 IPR:                 Initial pain reaction


Hr:                   Hour(s)


* Kay J H and Calandra J C (1962)


 


Table 4. Individual Total Scores and Group Mean Scores for Ocular Irritation Calculated from the Draize Scores



















































 


Rabbit Number and Sex



* Individual Total Scores At:



1


Hour



24


Hours



48


Hours



72


Hours



Male #1



4



2



0



0



Male #2



6



2



2



0



Male #3



6



2



2



0



* Group Total



16



6



4



0



* Group Mean Score



5.33



2.00



1.33



0.00



 *: Kay J H and Calandra J C (1962)


 


Table 5. Individual Fluorescein Staining





































 


Rabbit Number and Sex



Fluorescein Staining



24 Hours Prior to Instillation



24 Hours After Instillation



48 Hours After Instillation



72 Hours After Instillation



Male #1



-



-



-



-



Male #2



-



-



-



-



Male #3



-



-



-



-



- : Absence of Fluorescein Stain


 


Table 6. Individual Bodyweights and Bodyweight Change

































 


Rabbit Number and Sex



 


Individual Bodyweight (g)



 


Bodyweight Change (g)



Before treatment



End of experiment



Male #1



3328



3389



61



Male #2



3251



3307



56



Male #3



3110



3176



66


Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was graded as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the modified Kay and Calandra classification system.
Executive summary:

In an OECD TG 405 primary eye irritation study, performed under GLP, 0.1 g of the test item was instilled into the conjunctival sac of the left eye of each of 3 adult male New Zealand White rabbits. The untreated right eyes served as the control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test material instillation. Observations with fluorescein staining were made approximately 24 hours before treatment and then 24, 48 and 72 hours after treatment.

No mortality occurred during the study. An Initial Pain Reaction (IPR) score of 2 was observed in all animals.

The average cornea opacity, iris and chemosis score of all three animals over 24, 48 and 72 hours was 0. The average conjunctivae score of animal #1 at 24 h was 0.33 (redness), fully reversible within 48 h. The average conjunctivae score of animal #2 and #3 at 48 h was 0.67 (redness), fully reversible within 72h. 

Fluorescein staining was negative in all animals at all time points. As all signs of eye irritation had fully reversed, the study was terminated after a period of 72 hours observation. No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

The test item was graded as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the modified Kay and Calandra classification system.


Under the condition of this study and according to GHS criteria, the test substance was considered not to be irritating to the eyes of rabbits.