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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:
30 May 1996 to 09 October 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose for cross-reference:
other: read-across target
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read-across from Dioctyltin bis (2-ethylhexylmercaptoacetate) (DOTE) (CAS No. 15571-58-1), see attached justification.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
area
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0.67-0.67-0.33-1.33-0-0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0-0.33-0-1-0-0
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: All mean individual scores were 0

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate
EC Number:
239-622-4
EC Name:
2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate
Cas Number:
15571-58-1
Molecular formula:
C36H72O4S2Sn
IUPAC Name:
8-Oxa-3,5-dithia-4-stannatetradecanoic acid, 10-ethyl-4,4-dioctyl-7-oxo-, 2-ethylhexyl ester
Constituent 2
Reference substance name:
2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate (purity >98%)
IUPAC Name:
2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate (purity >98%)
Test material form:
liquid
Details on test material:
Physical description: clear colorless liquid
Storage conditions: original container stored at room temperature.

A sufficient amount of the material was transferred from the original container to a labeled storage vessel and stirred prior to dispensation and throughout the dosing procedure.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: males and females
- Body weights: 2828 and 4148 g at initiation of dosing
- Housing: individual suspended mesh-bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimitisation: minimum of six days


ENVIRONMENTAL CONDITIONS
Room temperature: 66.5 - 68.2 °F
Relative humidity: 49.0 - 69.9 %.
Photoperiod: 12 hours light/12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
undiluted amount applied: 0.1 mL
Duration of treatment / exposure:
96 hour(s)
Observation period (in vivo):
4 days.
Animals observed twice daily for mortality.

Both eyes of the rabbits were examined for occular abnormalities prior to initiation of dosing, including the use of sodium fluorescein and UV light for detection of corneal abnormalities. Both eyes were examined macroscopically for ocular irritation using a hand-held penlight in accordance with the method of Draize.
Number of animals or in vitro replicates:
3/sex
Details on study design:
Eyes were not rinsed; the test material was placed directly into the cupped lower conjunctival sac of the right eye.
Body weight recorded on day 0 and at termination.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Remarks:
area
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
6 animals
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0.67-0.67-0.33-1.33-0-0
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean individual scores : 0-0.33-0-1-0-0
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
6 rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
other: All mean individual scores were 0
Irritant / corrosive response data:
None of the rabbits vocalised upon installation of the test material.
The left (control) eyes were free of evidence of ocular irritation and other findings for the duration of the study.
There were no test material related deaths, clinical findings, or body weight changes during the study period. The maximum average score for the test material was 8.0 at one hour post instillation. Positive conjunctival irritation was noted for 4/6 rabbits. All animals had minor conjunctival irritation. There were no iridal or corneal findings. All irritation was reversible and completely subsided by day 4.
Other effects:
One female (no. 21091) lost 390g (14%) of initial (day 0) bodyweight. This weight loss was not considered to be related to test material administration. There were no other remarkable changes or differences observed in body weights during the study period.

Any other information on results incl. tables

Table 1. Individual ocular irritation scores for conjuctiva.

 Animal/sex 1h  (R-C-D) 24h (R-C-D)  48h (R-C-D)  72h (R-C-D)  4d  (R-C-D)
1 m 2 -1 -1 1 -0 -0 1 -0 -0 0 -0 -0  
2 m 2 -1 -1  1 -1 -0  1 -0 -0  0 -0 -0   
3 m 1 -1 -1  1 -0 -0  0 -0 -0  0 -0 -0   
4 f  2 -1 -2  2 -1 -0  1 -1 -0  1 -1 -0  0 -0 -0 
5 f  1 -1 -2  0 -0 -0  0 -0 -0  0 -0 -0   
6 f  2 -1 -1  0 -0 -0  0 -0 -0  0 -0 -0   
          

R-redness

C-chemosis

D-discharge

m-male

f-female

Table 2. Individual body weights (g).

Animal number Sex Initation (day 0) Termination (interval)
21044 m 2841 2898 (day 3)
21049 m 3159 3286 (day 3)
21055 m 2876 3027 (day 3)
20638 f 4148 4120 (day 4)
21072 f 3088 3125 (day 3)
21091 f 2828 2438 (day 3)

Applicant's summary and conclusion

Interpretation of results:
other: Not classified in accordance with EU Criteria
Conclusions:
Under the conditions of this study the test material was not irritating to the eye.
Executive summary:

The preliminary ocular irritation potential of the test material was evaluated in accordance with the stamdardosed guidelines OECD 405 and EPA OTS 798.4500, under GLP conditions.

During the study, single 0.1 mL doses of the test material were instilled into the lower conjuctival sac of the right eye of 6 New Zealand White rabbits. The eyelids were held closed for approximately 1 second and released. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all animals remained unwashed.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately 1, 24, 48, and 72 hours after dosing and on day 4 if irritation persisted. Sodium fluorescein was used to aid in revealing possible corneal damage at 24, 48, and 72 hours and on day 4. Postive conjunctival reactions were noted in the treated eye of 4 animals while minor conjuctival irritation was noted for all rabbits. There were no corneal or iridal findings. All irritation was reversible and completely subsided by day 4 or earlier.

Under the conditions of this study, the test material was not irritating to the eye.