Reaction products of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane and triacetoxyvinylsilane.

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (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

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Removed from study report
- Age at study initiation: 12 weeks
- Weight at study initiation: 2428-2661 g
- Fasting period before study: Not mentioned in report so assumed no fasting.
- Housing: Individually in suspended metal cages with perforated floors.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23.5
- Humidity (%): 31-45
- Air changes (per hr): 18
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 100 x 100 mm
- Coverage: approximately 10% of the total body surface area.
- Type of wrap if used: the treatment area was covered with porous gauze held in place with a non-irritating dressing and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- At the end of the 24 hour exposure period the dressings were carefully removed and the treated area of skin wiped with a towel moistened with warm water at 39°C to remove residual test substance.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.802 mL/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rabbits were observed at least twice daily for mortality and morbidity. The body weight of each animal was recorded on days 1 (prior to dosing), 8 and 15. Animals were observed immediately after dosing and at approximately hourly intervals for the remainder day 1 (approximately six hours). On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
- Necropsy of survivors performed: yes. After the final observation, all the rabbits were sacrificed and subjected to a macroscopic examination which consisted of examination of the treated skin site and underlying tissue, and opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
- Other examinations performed: The treated skin of each rabbit was examined once daily on day 2 through to day 15. At each interval, dermal irritation was assessed for erythema, eschar formation, oedema and any other lesion. Dermal responses were assessed using the Draize scoring system. Animals were clipped as needed to evaluate dermal responses. The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.

Statistics:

Group mean body weights were calculated. No other statistical analyses were carried out.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: No clinical signs were observed in any animal.

Gross pathology:

No abnormalities found.

Other findings:

Dermal responses: A predominantly well-defined level of irritation (erythema/oedema grade 2) was evident in all rabbits following removal of the dressings. A similar level of response was persistent during the first week of the study. By week two of the study, reactions had ameliorated in the majority of animals and although some erythema/oedema was still evident in five animals at study termination (day 15), reactions had resolved in the remaining five animals by the day of termination. These reactions were accompanied by some localised including necrosis, spots/scabbing and desquamation. These latter responses were still evident in nine of the ten animals at study termination.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The key study for acute dermal toxicity, conducted according to OECD TG 402 and in compliance with GLP (Dow Corning Corporation, 2000b), LD50 for alkoxy exchange product of vinyltriacetoxysilane and glycidoxypropyltrimethoxysilane was greater than 2000 mg/kg bw/day. The dermal reactions suggested that the test substance might cause severe irritation/corrosion following prolonged occlusive exposure.