Dibutyltin oxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 May 2010 to 26 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyltin oxide

EC Number:

212-449-1

EC Name:

Dibutyltin oxide

Cas Number:

818-08-6

Molecular formula:

C8H18OSn

IUPAC Name:

dibutylstannanone

Details on test material:

Sponsor's identification: CAS No 818-08-6
Description: white solid
Batch number: not supplied
Date received: 26 March 2010
Expiry date: 26 March 2011
Storage conditions: approximately 4°C in the dark under nitrogen

The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of the Sponsor.

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., Loughborough, UK.
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.38 kg
- Housing: The animal was housed in a suspended cage.
- Diet/water (e.g. ad libitum): Free access to mains drinking water and food (2030 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might 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 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 ml of the test material, which was found to weigh approximately 93 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made on Days 7 and 14 to assess the reversibility of the ocular effects.

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none
- Time after start of exposure: n/a

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

degree of opacity

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

not reversible

Results 2

Irritation parameter:

cornea opacity score

Remarks:

area of cornea involved

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not reversible

Irritant / corrosive response data:

Scattered or diffuse corneal opacity was noted in the treated eye at the 48, 72 Hour and 7 Day observations. Adverse ocular reactions prevented accurate evaluation of the cornea at the 14 Day observation.
Iridial inflammation was noted in the treated eye at the 24, 48, 72 Hour and 7 Day observations. Adverse ocular reactions prevented accurate evaluation of the iris at the 14 Day observation.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-Hour observations with severe conjunctival irritation noted at the 72 Hour, 7 and 14 Day observations.

Other effects:

Blepharitis was noted in the treated eye at the 72 Hour observation. Off white appearance of the majority of the nictitating membrane and lower conjunctival membrane was noted at the 7 and 14 Day observation. Pannus formation, over the whole of the cornea, and blood stained discharge were noted in the treated eye at the 14 Day observation.

Any other information on results incl. tables

Due to the worsening reactions and evidence of irreversible effects the animal was killed for humane reasons immediately after the 14-Day observation, in accordance with Company policy and current UK Home Office guidelines.

Table 1              Individual and Total Scores for Ocular Irritation

Rabbit Number and Sex	69203Male
	IPR= 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	14 Days K
CORNEA
Degree of Opacity	0	0	1	1	1	?cPa
Area of Cornea Involved	0	0	4	4	4	?c
IRIS	0	1	1	1	1	?i
CONJUNCTIVA
Redness	2	2	2	2	2P	2PBs
Chemosis	2	2	2	3Bp	3	3
Discharge	2	3	3	3	3	3

 

IPR = Initial pain reaction

P = Off white appearance of the majority of the nictitating membrane and lower conjunctival membrane

Bp = Blepharitis

Bs =Blood stained discharge

Pa = Pannus formation over the whole of the cornea

?c = Adverse ocular reactions prevented accurate evaluation of the cornea

?i = Adverse ocular reactions prevented accurate evaluation of the iris

K = Animal killed for humane reasons in accordance with Company policy and current UK Home Office guidelines

Applicant's summary and conclusion

Interpretation of results:

other: Eye damage (category 1) according to EU criteria

Conclusions:

The test material was considered to be corrosive to the rabbit eye due to the irreversible effects which persisted after 14 days.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

 OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

 Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

A single application of the test material to the non-irrigated eye of one rabbit produced scattered or diffuse corneal opacity, iridial inflammation and severe conjunctival irritation. Other ocular effects noted were blepharitis, off white appearance of the nictitating membrane and lower conjunctival membrane, blood stained discharge and pannus formation. Due to the worsening reactions and evidence of irreversible effects the animal was killed for humane reasons immediately after the 14 Day observation, in accordance with Company policy and current UK Home Office guidelines.

The test material was considered to be corrosive to the rabbit eye due to the irreversible effects noted.