3-(trimethoxysilyl)propyl isocyanate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29.06.1994 to 27.09.1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(trimethoxysilyl)propyl isocyanate

EC Number:

239-415-9

EC Name:

3-(trimethoxysilyl)propyl isocyanate

Cas Number:

15396-00-6

Molecular formula:

C7H15NO4Si

IUPAC Name:

(3-isocyanatopropyl)trimethoxysilane

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP, Inc (Denver, PA)
- Age at study initiation: 13-18 weeks
- Weight at study initiation: 2-2.3 kg
- Fasting period before study: No
- Housing: Individually in cages with wire floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-60
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29.06.1994 To: 27.09.1994

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal trunk
- % coverage: No data
- Type of wrap if used: Double layer of gauze sheeting was wrapped around the trunk and secured with adhesive tape. To secure the polyethylene, plastic ties/rubber bands were added (at the ends of the trunk). The sheeting was protected from removal or tearing by wrapping the trunk with bandage tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied: 15 mg/cm2 to 40 mg/cm2

Duration of exposure:

24 h

Doses:

Males: 500, 1000, 1400 and 2000 mg/kg bw.
Females: 1000, 1400 and 2000 mg/kg bw.

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Dosed animals were observed frequently for signs of toxicity on the first day of the test and twice per day thereafter. Weights were recorded on the day of dosing and at 7 and 14 days after dosing and at death.
- Necropsy of survivors performed: Yes
- Other examinations performed: Macroscopic examination.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 190 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In the definitive percutaneous test, 5 female rabbits were dosed with 2000 mg/kg of undiluted test substance (the maximum required dose - limit
test). Substantial signs of toxicity and 1 death resulted. Another 5 females were dosed with 1400 mg/kg of undiluted Y-5187; 1 animal died. None of 5 females died from 500 mg/kg. Most deaths occurred within 1 to 5 days. Three males died at 4 hours, 6 days or 9 days.

Clinical signs:

other: Signs of toxicity included hypoactivity, prostration, slow breathing, shallow breathing, an abnormal gait (in 2 ), rapid breathing, diarrhoea (in 1), front limb splay and marked hindlimb splay (in 1 male that died), marked weakness of right hind limb (in

Gross pathology:

Necropsy of rabbits that died revealed dark red areas on the lungs and single instances of light brown lungs, pale lungs with dark red areas, a dark red thymus, dark red liquid in the bladder and a distended bladder. The tissues of several animals that died were autolyzed upon necropsy. Gross necropsy findings for survivors included 1 dark red thymus and mottled and/or dark red areas on the lungs (in 2). One animal had a small, firm left kidney and a large right kidney.

Other findings:

Skin reactions included erythema, oedema, ecchymosis, ulceration, necrosis, fissuring, desquamation, alopecia and scabs. For most rabbits, the skin of
the dosed area was dry and leather-like at 1 day.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute dermal toxicity study conducted using a protocol comparable to OECD 402 and to GLP (reliability score 1) the LD50 values in male and female rabbits were 1190 and >2000 mg/kg bw, respectively for 3-(trimethoxysilyl)propyl isocyanate. There were signs of skin irritation. Signs of toxicity included hypoactivity, prostration, slow breathing, shallow breathing, an abnormal gait (in 2 ), rapid breathing, diarrhoea (in 1), front limb splay and marked hindlimb splay (in 1 male that died), marked weakness of right hind limb (in 1 male that died), weakened front limbs (in 1 male that died), pallor (in 2), an abnormal tilting of the head (in l), emaciation, iritis (in 1), dehydrated appearance (in 1), discharge or crust (mostly brown) on the perianal fur, and wetness of the perioral and perinasal fur. Most affected survivors recovered at 1 to 4 days. Two rabbits exhibited signs at 13 and/or 14 days.