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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:
between 27 July 2010 and 16 September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted to OECD guideline 405 and is considered adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
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
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibutyltin maleate
EC Number:
201-077-5
EC Name:
Dibutyltin maleate
Cas Number:
78-04-6
Molecular formula:
C12H20O4Sn
IUPAC Name:
dibutylstannanebis(ylium) (2Z)-but-2-enedioate
Details on test material:
Sponsor's identification: CAS No 78-04-6
Description: White powder
Chemical name: Dibutyltin maleate
Purity: >98% w/w
Impurities (identity and concentrations): Dibutyltin oxide (818-08-6) <1%, Maleic anhydride <1%
Batch number: 190 001 10/1
Date received: 15 April 2010
Expiry date: 08 September 2010
Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Loughbrough, UK.
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.05 to 2.76 kg
- Housing: individually housed in suspended cages.
- Diet: 2030 Teklad Global Rabbit diet (Harlan Laboratories U.K. Ltd., Oxon, UK), allowed throughout the study (considered not to contain any contaminent at a level that may have affected the purpose or integrity of the study)
- Water: Free access to mains water throughout the study (considered not to contain any contaminent at a level that may have affected the purpose or integrity of the study)
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and twelve hours darkness.

(The animals were provided with environmental enrichment items considered not to contain any contaminent at a level that may have affected the purpose or integrity of the study)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approximately 85 mg)
Duration of treatment / exposure:
72 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): Washing not performed

SCORING SYSTEM:
- Eye irritation: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49, presented as table 2 under section "Any other information on materials and methods incl. tables"
- Initial pain reaction: presented as table 1 under section "Any other information on materials and methods incl. tables"

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: opacity worsened to score 2 at day 7
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
1.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean 24, 48, 72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean 24, 48, 72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24, 48, 72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24, 48, 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24, 48, 72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
other: Blepharitis, Petechial haeorrhage covering the whole of the nictitating membrane, blood stained discharge
Basis:
animal #3
Remarks on result:
other: Due to worsening reactions and signs of pain and discomfort, this animal was killed for humane reasons immediately after the 72 hour observation
Irritant / corrosive response data:
Scattered or diffuse corneal opacity was noted in all treated eyes at the 24 and 48-Hour observations. Translucent corneal opacity was noted in one treated eye and scattered or diffuse corneal opacity was noted in two treated eyes at the 72-Hour observation. Translucent corneal opacity was noted in one treated eye at the 7-Day observation with scattered or diffuse corneal opacity noted at the 14-Day observation.

Iridial inflammation was noted in all treated eyes at the 24 and 48-Hour observations, in two treated eyes at the 72-Hour observation and in one treated eye at the 7-Day observation.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Severe conjunctival irritation was noted in one treated eye and moderate conjunctival irritation was noted in two treated eyes at the 24 and 48-Hour observations. Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye at the 72-Hour observation. Moderate conjunctival irritation was noted in one treated eye at the 7-Day observation with minimal conjunctival irritation noted at the 14-Day observation.

Petechial haemorrhage covering the whole of the nictitating membrane was noted in all treated eyes at the 24 and 48-Hour observations and in two treated eyes at the 72-Hour observation. A pale area, off white in appearance and approximately 10 mm x 10 mm in size, was noted on the lower conjunctival membrane of one treated eye at the 7 and 14-Day observations. Other ocular effects noted in one treated eye at the 72-Hour observation were blepharitis and blood stained discharge.

Due to worsening reactions and signs of pain and discomfort, one animal was killed for humane reasons immediately after the 72-Hour observation, in accordance with the laboratory’s Company policy and current UK Home Office guidelines.
Other effects:
Bodyweight loss was noted in the animal that was humanely killed immediately after the 72-Hour observation. The remaining two animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 3: Measurement of pH

Preparation

pH Measurement

Immediately

After 10 minutes

After 10 minutes

10% w/w aqueous preparation of the test item

3.2

2.4

2.1

 

Table 4: Individual Scores for Occular Irritation

Rabbit Number and sex

69468 Male

69524 Male

69602 Male

IPR = 0+

IPR = 0+

IPR = 0+

 

1 Hr

24 Hr

48 Hr

72 Hr

7 Dy

14 Dy

21 Dy

1 Hr

24 Hr

48 Hr

72 Hr

7 Dy

1 Hr

24 Hr

48 Hr

72 Hr

Cornea

 

Degree of opacity

0

1

1

1

2

1

0

0

1

1

1

0

0

1

1

2

Area of cornea involved

0

4

3

3

2

1

0

0

3

2

1

0

0

4

4

4

Iris

0

1

1

1

1

0

0

0

1

1

0

0

0

1

1

1

Conjunctivae

 

Redness

2

2

2

2

2

1

0

2

2

2

1

0

2

2

2

2

Chemosis

2

3

2

2

2

1

0

2

2

2

1

0

2

2

2

3

Discharge

2

3

3

3

1

0

0

2

2

2

1

0

2

2

2

2

Other ocular reactions

-

Pt

Pt

Pt

P

P

-

-

Pt

Pt

-

-

-

Pt

Pt

PtBpBsK

IPR = Initial pain reaction

+ = One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

Hr = Hour(s)

Dy = Days

Pt = Petechial haemorrhage covering whole of the nictitating membrane

Bp = Blepharitis Bs = Blood stained discharge

P = Pale area, off white cream coloured in appearance, approximately 10 mm x 10 mm in size, on lower conjunctival membrane

K = Animal killed for humane reasons

- = Not applicable

 

Table 5: Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

69468 Male

Day 0

Day 21

0.28

2.76

3.04

69524 Male

Day 0

Day 7

0.19

2.05

2.24

69602 Male

Day 0

Day 3

-0.02

2.40

2.38

Applicant's summary and conclusion

Interpretation of results:
other: serious damage to the eyes
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The test item produced irreversible effects and was considered to cause serious damage to the rabbit eye. The substance is therefore considered to be classifed accordingly.
Executive summary:

The study was performed to assess the irritancy potential of the test item (dibutyltin maleate) to the eye of the New Zealand White rabbit. The study was performed to the guidelines OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002) and Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008.

 

A single application of the test item to the non-irrigated eye of three rabbits produced scattered or diffuse or translucent corneal opacity, iridial inflammation and moderate to severe conjunctival irritation. Other ocular effects noted were a pale area on the conjunctival membrane and/or petechial haemorrhage of the nictitating membrane. Other ocular effects noted in one treated eye were blepharitis and blood stained discharge. Due to worsening reactions and signs of pain and discomfort, one animal was killed for humane reasons immediately after the 72-Hour observation, in accordance with Company policy and current UK Home Office guidelines.

The test item produced irreversible effects and was considered to cause serious damage to the rabbit eye. The substance is therefore considered to be classifed accordingly.