2-Propenoic acid, 2-methyl-, tris(1-methylethyl)silyl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 June 2010 to 15 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent study conducted by a GLP certified laboratory in accordance OECD, EPA and EU guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

EC Number:

700-182-8

Cas Number:

134652-60-1

Molecular formula:

C13 H26 O2 Si

IUPAC Name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

Details on test material:

- Name of test material (as cited in study report): TIS-M
- Lot/batch No.: 9925
- Storage condition of test material: Room temperature
- Date of manufacture: 23 September 2009
- Expiry date: 02 December 2010

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXI-COOP Ltd. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 200 g and 300 g
- Fasting period before study: No information.
- Housing: Individual caging
- Diet: Ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany ad libitum.
- Water: Water from the municipal supply, as for human consumption from 500 ml bottle ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 1 June to 15 June 2010

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE

- Area of exposure: The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24- hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

- % coverage: Approximately 10 % area of the total body surface

- Type of wrap if used: Semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE

- Washing (if done): The area of skin treated with the test item was washed with water of body temperature.

- Time after start of exposure: 24 hours

TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 2000/mg/kg/bw

- Concentration (if solution): Undiluted

- Constant volume or concentration used: yes

- For solids, paste formed: Not applicable

Duration of exposure:

24 hours

Doses:

2000 mg/kg/bw

No. of animals per sex per dose:

5 male/5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: Clinical observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. All animals were anaesthetised with Euthasol®40% and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after a 24-hour dermal exposure of TIS-M administered at 2000 mg/kg bw to CRL:(WI)BR rats followed by a 14-day observation period.

Clinical signs:

No clinical signs were observed after the treatment with the test item or during the 14-day observation period.

Body weight:

The body weight and body weight gain TIS-M treated animals did not show any test item-related effect.

Gross pathology:

A single 24-hour dermal administration TIS-M to the CRL:(WI) BR rat at a dose level of 2000 mg/kg bw, followed by a 14 day observation period, was not associated with any test item-related macroscopic findings.

Other findings:

After treatment with TIS-M red skin was observed in 6/10 animals. Wound and skin scabs were also noted in two female animals. There were no dermal signs noted from Day 8.

Any other information on results incl. tables

INDIVIDUAL CLINICAL OBSERVATIONS STUDY CODE: 09/285-002P TEST SYSTEM: CRL:(WI)BR RAT TEST ITEM: TIS-M

Group No

Sex

Dose Level(mg/kg)

Animal Number

Observations

Observation days

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

Male

2000

9890

Symptom Free

+

+

-

+

+

+

+

+

+

+

+

+

+

+

+

+

15/16

Skin Red

+

1/16

2

9891

Symptom Free

+

+

-

+

+

+

+

+

+

+

+

+

+

+

+

+

15/16

Skin Red

+

1/16

3

9892

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

9893

Symptom Free

+

+

-

+

+

+

+

+

+

+

+

+

+

+

+

+

15/16

Skin Red

+

1/16

5

9894

Symptom Free

+

+

-

+

+

+

+

+

+

+

+

+

+

+

+

+

15/16

Skin Red

+

1/16

6

Female

2000

9895

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

7

9896

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

8

9897

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

9

9898

Symptom Free

+

+

+

+

+

+

+

+

+

9/16

Skin Red

+

1/16

Wound

-

-

-

+

+

2/16

Scab

+

+

+

+

4/16

10

9899

Symptom Free

+

+

+

+

+

+

+

+

+

+

+

11/16

Skin Red

+

1/16

Wound

+

1/16

Scab

-

-

-

-

+

+

+

3/16

Remarks: Severities: 1=Slight/Small/Few; 2=Moderate/Medium; 3=Marked/Large/Many +: increased, or present; -: decreased, or absent

Treatment day = Day 0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item TIS-M was found to be higher than 2000 mg/kg body weight in male and female CRL:(WI)BR rats.

Executive summary:

An acute dermal toxicity study was performed with test item TIS-M in CRL:(WI)BR rats, in compliance with OECD Guideline No.: 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex;). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period. Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Rats were euthanized and a gross macroscopic examination performed at the end of the 2-week observation period (Day 14). The results of the study were summarized as follows:

 

Mortality

No mortality occurred.

Systemic clinical signs

No clinical signs were observed after the treatment with the test item or during the 14-day observation period.

Local dermal signs

After treatment with TIS-M red skin was observed in 6/10 animals. Wound and skin scabs were also noted in two female animals.

Body weight

The body weight and body weight gain of TIS-M treated animals did not show any test item-related effect.

Necropsy

There were no test item-related macroscopic findings observed at necropsy.

Conclusions

The acute dermal median lethal dose (LD50) of the test item TIS-M was found to be higher than 2000 mg/kg bw in male and female CRL:(WI)BR rats.