Bis(tributyltin) oxide

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

ZK 113.599 (solid)

IUPAC Name:

ZK 113.599 (solid)

Test animals

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

Test system

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Score:

1.9

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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.

Applicant's summary and conclusion

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.