Dibutyltin oxide

Endpoint summary

Description of key information

Eye:

in vitro: In an in vitro eye irritation study the test material was assessed using the SkinEthic Reconstituted Human Corneal model. According to the protocol followed the test material was considered to be a Non-Irritant (NI) and so an in vivo test was carried out.

In the in vivo study (Sanders, 2010) the test material was considered to be corrosive to the rabbit eye due to the irreversible effects noted. (OECD 405).

Skin:

Dibutyltin oxide was evaluated for dermal irritation on New Zealand White rabbits using methods similar to OCED guidelines.

There were no deaths or significant body weight changes during the study period. There was no evidence of corrosion following the three-minute, sixty-minute and four-hour exposures. Dermal irritation following the four-hour exposure included very slight to moderate erythema, very slight to slight edema and desquamation on all sites. All edemas completely subsided within 72 hours of application. Very slight to slight erythema persisted through day 14 for all four-hour sites. Based on the data, dibutyltin oxide was found to be non-corrosive when applied under occlusion to the shaved, intact skin of albino rabbits for up to 4 hours.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 4-18, 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc. , Denver, Pennsylvania
- Age at study initiation: Young adult
- Weight at study initiation: 3142 to 3482 grams
- Housing: Individual suspended wire-mesh cages at the WIL Research Laboratories
- Diet (e.g. ad libitum): Ad libitum, Purina Certified Rabbit Chow #5322
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days
- Method of Identification: Eartag

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22 °C
- Humidity (%): 32-70%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Type of coverage:

other: The 3- and 60-minute exposures were occluded for the corrosion study, and the four-hour exposure was semi-occluded for the irritation study

Preparation of test site:

shaved

Vehicle:

water

Remarks:

For the 3- and 60-minute exposures, materials were not be moistened with water, but for the 4 hour exposure, the solid materials were moistened with deionized water

Controls:

not specified

Amount / concentration applied:

For the 3- and 60-minute exposures, 0.5 grams/site
For the 4-hour exposure, 0.5 grams/site

Duration of treatment / exposure:

Three treatments:
3-minute exposure
60-minute exposure
4-hour exposure

Observation period:

3-minute exposure: 24 and 48 hours after dosing
60-minute exposure: 24 and 48 hours after dosing
4-hour exposure: 30 minutes, 60 minutes, 24, 48, and 72 hours after dosing, and daily thereafter through day 14

Number of animals:

Six

Details on study design:

TEST SITE
- Area of exposure: Dermal surface of shaved backs and flanks
- % coverage: 2.5 cm x 2.5 cm gauze patch
- Type of wrap if used: Patches were overwrapped with plastic wrap for the 3- and 6-minute occluded exposures and gauze bandaging for the four-hour semi-occluded exposure. Bandaging materials were secured with Dermiform Tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Sites were wiped with disposable paper towels moistened with tepid tap water
- Time after start of exposure: Either 3-minutes, 60-minutes, of 4 hours after exposure.

SCORING SYSTEM: Draize method (Table 3)

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1.83

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

1.67

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

1.83

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

14 d

Score:

1.83

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: disquamination was seen in all rabbits

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

0.17

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

There was no evidence of corrosion following the three-minute, sixty-minute and four-hour exposures. Dermal irritation following the four-hour exposure included very slight to moderate erythema, very slight to slight edema and desquamation on all sites. All edema completely subsided within 72 hours of application. Very slight to slight erythema persisted through day 14 for all sites.

Other effects:

There was no evidence of corrosion following the 3- and 60-minute and 4-hour exposures to the test material. No irritation greater than very slight to slight erythema and no edema was observed on any three or 60-minute exposure site at both 24 and 48 hours post-exposure.

The test material induced very slight to moderate erythema and very slight to slight edema on all rabbits following the four-hour exposure. All sites had desquamation by day 11. There were no other dermal findings. Edema completely subsisted within 72 hours. Very slight to slight erythema was present on all sites at study termination (day 14).

There was no evidence of corrosion following the three- and 60- minute and 4-hour exposures to the test material. No irritation greater than very slight to slight erythema and no edema was observed on any three or 60 -minute exposure site at both 24 and 4 hours post-exposure.

The test material induced very slight to moderate erythema and very slight to slight edema on all rabbits following the four-hour exposure- All sites had desquamation by day 11. There were no other dermal. findings. Edema completely subsided within 72 hours. Very slight to slight erythema was present on all sites at study termination (day l4).

There were no deaths or significant body weight changes during the study period.

See attached tables for results.

Interpretation of results:

other: Skin irritant (category 2) according to EU criteria

Conclusions:

There were no deaths or significant body weight changes during the study period. There was no evidence of corrosion following the 3-minute, 60-minute, and 4-hour exposures. Dermal irritation following the 4-hour exposure included very slight to moderate erythema, very slight to slight edema and desquamation on all sites. All edema completely subsided within 72 hours of application. Very slight to slight erythema persisted through day 14 for all sites.

Executive summary:

Dibutyltin oxide was evaluated for dermal irritation on New Zealand White rabbits.

Single 0.5 g doses of the test material were applied to the shaved, intact skin of 6 albino rabbits under occlusive dressings for three and 60 -minute application sites and under semi-occlusive dressings for a four-hour expsoure period. The three and 60 minute application sites were observed immediately after bandage removal and at approximately 24 and 48 hours after dosing for the presence or absence of corrosion. The four hour exposure sites were washed immediately following bandage removal.

There were no deaths or significant body weight changes during the study period. There was no evidence of corrosion following the three-minute, sixty-minute and four-hour exposures. Dermal irritation following the four-hour exposure included very slight to moderate erythema, very slight to slight edema and desquamation on all sites. All edemas completely subsided within 72 hours of application. Very slight to slight erythema persisted through day 14 for all four-hour sites. Based on the data, dibutyltin oxide was found to be non-corrosive when applied under occlusion to the shaved, intact skin of albino rabbits for up to 4 hours.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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

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)

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.

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.

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

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

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Eye irritation

In an in vitro eye irritation study (Warren, 2010) the test material was assessed using the SkinEthic Reconstituted Human Corneal model. According to the protocol followed the test material was considered to be a Non-Irritant (NI) and so an in vivo test was carried out.

In the in vivo study (Sanders, 2010) the study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit.

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.

Skin irritation

In the in vivo study (Kiplinger, 1994) the study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.

A reliability rating of 2 was assigned to this study as the study was conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Eye:

According to EC/1272/2008 the test material will be classified as Eye Dam. Cat. 1; H318: Causes serious eye damage.

 

Skin:

According to EC/1272/2008, the test substance will be classified as Skin Irrit. Cat. 2; H315: Causes skin irritation.