3-(trimethoxysilyl)propyl isocyanate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24.05.2004 to 16.12.2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation 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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, North Carolina
- Age at study initiation: 8-10 weeks old
- Weight at study initiation: Males: 272-298 g; Females: 232-257 g.
- Fasting period before study: No data
- Housing: Individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 50± 20
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.09.2004 To: 01.10.2004

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume:
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air:
- System of generating particulates/aerosols:
- Method of particle size determination:
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: yes/no

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

3.9, 11.0 and 17.8 ppm (actual)

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: Clinical observations were made following exposure on study day 0 and once daily thereafter for 14 days. Body weights were obtained immediately prior to exposure on study day 0 and on post-exposure days 7 and 14. All animals that died during the study were weighed.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

15 ppm

Based on:

test mat.

95% CL:

>= 12 - <= 18

Exp. duration:

4 h

Mortality:

Mortality was 0/10, 1/10 and 8/10 animals for the 3.9, 11.0 and 17.8 ppm groups, respectively.
One male in the 11.0 ppm group was found dead on the day following exposure (study day 1). Five males and three females in the 17.8 ppm group were found dead during the study. All deaths were noted within four days of exposure.

Clinical signs:

other: Clinical observations immediately following exposure included rales in all groups; gasping and laboured respiration in the 11.0 and 17.8 ppm groups; and hypoactivity and hypothermia in the 17.8 ppm group. Significant clinical observations for the survivin

Body weight:

Two females in the 3.9 ppm group lost weight during study days 7 and 14 and three males and one female in the 11.0 ppm group lost weight during study days 0 to 7. Both of the surviving females in the 17.8 ppm group lost weight during study days 0 to 7. With the exception of one female in the 3.9 ppm group, all animals surpassed their initial body weight by study day 14 and were considered normal.

Gross pathology:

There were no gross findings for the male found dead in the 11.0 ppm group. For the animals found dead in the 17.8 ppm group, the only internal gross findings were lungs not fully collapsed for one male. At the scheduled necropsy, dark red discolouration of the mandibular lymph node was noted for one female each in the 11.0 and 17.8 ppm groups.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

In an acute vapour inhalation study conducted to OECD 403 and to GLP (reliability score 1) the LC50 for a 4-hour exposure to 3-(trimethoxysilyl)propyl isocyanate was 15 ppm (125.95 mg/m3) in rats. Clinical observations immediately following exposure included rales in all groups; gasping and laboured respiration in the 11.0 and 17.8 ppm groups and hypoactivity and hypothermia in the 17.8 ppm group. Significant clinical observations for the surviving animals during the 14-day post-exposure observation period consisted of rales in all groups; decreased defecation/urination, hypothermia and laboured respiration in the 11.0 and 17.8 ppm groups, and gasping and hypoactivity in the 17.8 ppm group. All animals in the 3.9 ppm group were considered normal by study day 2. Surviving animals in the 11.0 and 17.8 ppm groups were considered normal by study days 9 and 7, respectively. There were no gross findings for the male found dead in the 11.0 ppm group. For the animals found dead in the 17.8 ppm group, the only internal gross findings were lungs not fully collapsed for one male. At the scheduled necropsy, dark red discolouration of the mandibular lymph node was noted for one female each in the 11.0 and 17.8 ppm groups.