Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 June 2012 to 04 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
see below
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
see below
Principles of method if other than guideline:
Due to a technical error, the day 3 clinical observations for two females were not recorded. This deviation was considered not to affect the integrity of the study.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid (unspecified)
Details on test material:
- Name of test material (as cited in study report: ethyl 9,9-dioctyl-4,7,11-trioxo-3,8,10-trioxa-9-stannatetradeca-5,12-dien-14-oate
- Physical state: extremely pale yellow liquid
- Storage condition of test material: approximately 4 °C in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: RccHan:WIST
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200 g
- Housing: animals were housed individually during the 24 hour exposure period and in groups of up to 4, by sex, for the remainder of the study in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Rodent diet, ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 13 June 2012 To: 4 July 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: on the day before treatment the back and flanks of each animal were clipped free of hair
- % coverage: approximately 10 % of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material

TEST MATERIAL
- The appropriate amount of test material was moistened with arachis oil BP and applied as evenly as possible to the area of shorn skin
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females.
Control animals:
no
Details on study design:
In the absence of data suggesting the test material was toxic, one male and one female rat were initially treated with the test material at a dose level of 2000 mg/kg bodyweight. As no mortalities were noted, a further group of 4 male and 4 female animals were similarly treated at a dose level of 2000 mg/kg bodyweight to bring the total of each sex to 5.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and once daily thereafter. The test site was observed daily for evidence of primary irritation and scored according to Draize (1977). Individual bodyweights were recorded prior to application of the test material on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes. Animals were killed by cervical dislocation. All animals were subjected to gross necropsy, consisting of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
One female showed bodyweight loss during the first week but expected gain in bodyweight during the second week and one female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Signs of dermal irritation noted were very slight erythema, crust formation and desquamation. There were no signs of dermal irritation noted at the test site of one male.

Any other information on results incl. tables

Table 1: Individual Dermal Reactions

Animal no. and sex

Observation

Effects noted after initiation of exposure (days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1 -0 M

Erythema

1

1

1

1

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

D

Cf

Cf

Cf

Cf

D

D

0

3 -0 M

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3 -1 M

Erythema

1

0

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

0

0

0

0

0

0

0

0

3 -2 M

Erythema

1

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3 -3 M

Erythema

1

0

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

0

0

0

0

0

0

0

0

2 -0 F

Erythema

1

1

0

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4 -0 F

Erythema

1

0

0

0

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

D

0

0

0

0

0

0

0

4 -1 F

Erythema

1

0

1

1

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

0

0

0

0

0

0

0

0

4 -2 F

Erythema

1

0

1

1

1

1

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

0

0

0

0

0

0

0

0

4 -3 F

Erythema

1

1

1

1

1

1

1

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

D

D

D

D

0

0

0

0

0

0

0 = no reactions

D = desquamation

Cf = crust formation

Table 2: Individual Bodyweights and Weekly Bodyweight Changes

Animal no. and sex

Bodyweight (g) at day

Bodyweight change (g) during week

0

7

14

1

2

1 -0 M

350

361

376

11

15

3 -0 M

260

285

299

25

14

3 -1 M

255

276

299

21

23

3 -2 M

244

275

308

31

33

3 -3 M

234

256

289

22

33

2 -0 F

230

227

237

-3

10

4 -0 F

217

220

224

3

4

4 -1 F

200

210

218

10

8

4 -2 F

214

223

221

9

-2

4 -3 F

206

213

218

7

5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the LD50 of the test material in the Wistar strain rat was determined to be greater than 2000 mg/kg bw and the test material requires no classification in accordance with EU criteria.
Executive summary:

The acute dermal toxicity of the test material was investigated in accordance with the standardised guidelines OECD 402 and EU Method B.3. During the study, a group of ten animals (five males and five females) was given a single 24 hour, semi-occluded dermal application of the test material to intact skin clipped free of hair at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

During the study there were no deaths and no signs of systemic toxicity were observed. One female showed bodyweight loss during the first week but expected gain in bodyweight during the second week and one female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period. Signs of dermal irritation noted were very slight erythema, crust formation and desquamation. There were no signs of dermal irritation noted at the test site of one male. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was therefore determined to be greater than 2000 mg/kg bw and the test material requires no classification in accordance with EU criteria.