Bis(tributyltin) oxide

Endpoint summary

Description of key information

Skin irritation:

As there was variability in the results and apparent interferences of the vehicles selected in the available studies, the conclusions from the review authored by Schweinfurth H (1986) encorporated all of the available studies for assessment.

The reactions produced by the formulations containing tributyltin compounds and the vehicle (Kristallol 60 + Alkydal F 67) on human skin were not significantly different from one another in the Friedman-test for exposure periods until 4 hours. The observed local irritation was predominantly attributed to the vehicle. Additional changes due to the tributyltin compounds did not occur in the volunteers.

The animal species showed a considerable variation with regard to duration, intensity as well as the type of local changes. While the rabbit does not seem to be suitable for a reliable prediction of the human skin reaction after contact with the formulations under investigation, the rat appears to be the animal species which mimics most closely the human reaction.

Eye irritation:

Tributyltin oxide was reported as highly irritating to the eyes.

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:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline available

Principles of method if other than guideline:

On either side of the spine of 12 male hairless mice, a skin area of 1 cm x 2 cm was marked with a coloured marker. These 24 application sites were distributed to the four formulations tested. 6 skin areas were applied with 0.16 g ZK 113.599/0.16 mL aqua bidest. (formulation C), wherease another 6 skin areas were applied with 0.08 mL aqua bidest. (formulation D) for the same time. The remaining 12 application sites were treated with 2 other formulations (A and B). Each application site was covered with a piece of gauze. The gauze was fixed on the skin using a Leukoflex bandage around the trunk. After exposure, the gauze and Leukoflex were removed and the test sites wiped with luke warm water and cotton wool. Test sites were observed 30-60 minutes after exposure and thereafter every 24 hours until day 15 of the test. Evaluation of the local tolerance on the skin of the hairless mouse after a single application was performed according to the score system of Draize J.H. in "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics". On day 15, the animals were sacrificed by CO2 inhalation. Necropsy was not performed.

GLP compliance:

yes

Species:

mouse

Strain:

other: hairless

Details on test animals or test system and environmental conditions:

Breeder: OLAC, England
Acclimitazation time: 28 d
Housing: conventional macrolon type 2, 1 animal per cage
Body weight: 28-38 g
Diet: food (altromin R pellets and tap water ad libitum
Environment: temperature 22-23°C, relative humidity 40-70%, 12 h light dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

other: not applicable

Vehicle:

other: aqua bidset

Controls:

yes, concurrent vehicle

Amount / concentration applied:

0.16mg/ 0.16 mL aqua bidest

Duration of treatment / exposure:

Application in the morning
Animals in restraining cages
After exposure, areas wiped off with warm water

Observation period:

30-60 min after expsoure and daily for 15 days

Number of animals:

6 males (test material exposure); 6 males (control animals)

Details on study design:

6 skin areas (per animal ) were applied with test material

Irritation parameter:

primary dermal irritation index (PDII)

Score:

1.9

Irritation parameter:

erythema score

Basis:

animal: 2M, 3M, 8M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal: 5M, 9M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal: 11M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Irritation parameter:

edema score

Basis:

animal: 2M, 8M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal: 3M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal: 5M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 15 days

Irritation parameter:

edema score

Basis:

animal: 9M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal: 11M

Remarks:

(mean)

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 15 days

Irritant / corrosive response data:

Transient slight reddening (2 animals) and swelling (4 animals), sporadically moderate swelling (1 animal), desquamation (2 animals), skin lesions (one animal) scab formation (3 animals) and scar formation (2 animals) were observed after ZK 113.599.
Pale area of administration was observed in 4 animals each after ZK 113.599 as well as after the control, but after ZK 113.599 this finding was more frequent.
Two animals showed no local finding from day 1 to day 15 of the test after treatment with ZK 113.599. The other 4 animals treated with ZK 113.599 were without local findings beginning on day 6-14 of the test except two animals (nos. 5M, 11M) showing scar formation.

Other effects:

Animal no. 10M showed on day 4-5 apathy and emaciation and was found dead on day 6 of the test. Necropsy revealed: probably gastric bleeding. This finding was not considered to be substance-related, but was presumably due to stress by restrained measurements.

Interpretation of results:

other: Classified for skin irritation (category 2) according to EU criteria

Conclusions:

The irritation index according to Draize was 1.92, indicating slight local incompatibility reactions. Overall the test material was classified as slight to moderate local irritation.

Executive summary:

The local dermal tolerance of a formulation containing 50% w/v tri-n-butyltinoxide (ZK 113.599) in comparison to the vehicle was tested on the intact skin of 6 male hairless mice each after a single application. On 6 skin areas of 1 cm x 2 cm were treated with a paste containing 0.16 g/0.16 ml aqua bidest for 4 h. Another 6 skin areas were treated with 0.08 ml aqua bidest for the same time under semi-occlusive conditions. The local reactions were recorded within 30 - 60 minutes after exposure and thereafter once daily until day 15 of the test. Transient slight to moderate swelling, slight reddening, desquamation, skin lesions, scab and scar formation were observed after exposure. Pale area of administration was observed after exposure more frequent as in controls.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

other: summary of experimental results

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

no guideline followed

Principles of method if other than guideline:

A short abstract reviewing literature on TBTO reporting the substance as highly incompatible for the eyes of rabbits at 0.15-2% in an aqueous formulation.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

0.15-2.0%

Duration of treatment / exposure:

No information

Observation period (in vivo):

No information

Number of animals or in vitro replicates:

No information

Remarks on result:

other: Test material was reported to be highly incompatable in the eyes.

Irritant / corrosive response data:

Test material was reported to be highly incompatable in the eyes. in consideration of these findings as well as those of the results on skin tolerance, studies on the effects of tributyltin compounds on the rabbit eye were not performed on ethical grounds.

Conclusions:

In a review of the literature, aqueous solutions of the test material were found to be highly incompatable with the eyes of rabbits. Further testing was not performed on ethical grounds.

Executive summary:

In a review of the literature, aqueous solutions of the test material were found to be highly incompatable with the eyes of rabbits. Further testing was not performed on ethical grounds.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

The studies provided for the data-requirement for skin irritation/corrosion were provided for information purposes only. Schobel-Wegner C (1985) was assigned a reliability score of 2, the study used a non-standard species than specified in the international harmonised guidelines without justification for the species selection. The further three studies were all assigned reliability scores of 4 as the reliability of the data was not assignable from the level of reporting. The conclusions from the review Schweinfurth (1986) encompassed all of the study data.

Eye irritation:

Schweinfurth H (1986) was provided for information purposes. The data was sourced from a review of previous studies and literature as was assigned a reliability score of 4 (not assignable) as the quality of data could not be determined from the limited reporting.

Justification for classification or non-classification

The substance is included in the group of substances "tributyltin compounds" which is itself included in Annex VI to Regulation (EC) No 1272/2008 with Index Number 050-008-00-3. The

substance is classified as H315 and H319 (causes skin irritation and causes serious eye irritation).