N-[3-(triethoxysilyl)propyl]ethylenediamine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 Aug - 21 Nov 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

EC Number:

225-806-1

EC Name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

Cas Number:

5089-72-5

Molecular formula:

C11H28N2O3Si

IUPAC Name:

N-[3-(triethoxysilyl)propyl]ethylenediamine

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 185-223 g (males), 184-221 g (females)
- Fasting period before study: no data
- Housing: 5 animals per cage (Makrolon type-4)
- Diet: Rattendiaet Altromin 1324, Altromin GmbH, Lage/Lippe, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 50± 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel/glass exposure chamber
- Exposure chamber volume: 60 l
- Method of holding animals in test chamber: animals are placed in plastic tubes (only nose exposed to the exposure chamber)
- Source and rate of air: clean air at 800 l/h
- System of generating particulates/aerosols: The test substance is injected in a two component nozzle. Primary aerosol was produced in a round bottom flask. Secondary aerosol reached the inhalation chamber through an ascending pipe.
- Method of particle size determination: Anderson-Kaskadenimpaktor Mark III, Anderson Samplers INC, Atlanta, USA
- Treatment of exhaust air: Aerosol in the inhalation chamber was aspirated through an A2-respiratory protection filter, a washing bottle filled with methanol, a washing bottle with water, a Bühlerfilter and a CaCl2 bottle. Substance leaking from the exposure chamber was aspirated and neutralized by a gas cleaning plant.
- Temperature, humidity, pressure in air chamber: 20.7 - 22.4°C; 12.2 - 30.3%, negative pressure

TEST ATMOSPHERE
- Brief description of analytical method used:
Gravimetric analysis: Atmosphere was aspirated through a gas meter and glass- and membrane filters (0.65 µm) every 15 minutes (Flow rate: 1.25 m/s). Filters were weighed before and after every measurement.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 100% of the particles had a diameter <10.3 µm. 5% to 22% of the particles were <0.6 µm (see table 2)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.9-1.4 / 1.6-2.2

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

0.23, 0.83, 1.78, 5.06 mg/l (analytical)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behaviour was checked during exposure and twice daily until day 15. Weight was determined at day 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

LC50 derivation: Probit method

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

1.1 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

1.18 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.23 mg/l: 1/5 (male), 0/5 (female)
0.83 mg/l: 1/5 (male), 1/5 (female)
1.78 mg/l: 3/5 (male), 4/5 (female)
5.06 mg/l: 5/5 (male), 5/5 (female)

Clinical signs:

other: 0.23 mg/l: male: panting, irregular respiration, coat bristling, uncoordinated gait, nasal discharge (blood coloured) were observed at the day of exposure and day 2. Sneezing was observed from day 2 to 4. From day 5 no abnormalities were observed. female:

Body weight:

Slightly reduced body weight gain was observed in the week after dosing with a dose-response relationship (see table 1).

Gross pathology:

Animals that died showed some abnormalities of the lung (except in the high dose group): red coloured lungs, emission of foam on dissection (males), plethoric (males), patchy dark red
Animals that survived until the end of the study showed no abnormalities.

Other findings:

Irregular respiration was observed immediately after start of exposure at any concentration tested. Nasal discharge (blood coloured) was observed in all dose groups, but the onset was concentration dependent starting 3 h after start of exposure in the low concentration group and after 30 min in the 1.78 mg/l group. In the high dose group no nasal discharge was observed, which was based on the fact that the animals of the 5.06 mg/l group died within 0.5 and 2.5 h. The effects observed indicate that the substance induces respiratory irritation including cytotoxic effects. These effects are concentration dependent and were observed before mortality occurred. Based on the clinical signs and the pathology findings in the lung it can be assumed that the local effects are accountable for the mortality.

Any other information on results incl. tables

Table 1: Body weights and body weight gain of the animals in the acute inhalation study.

Dose group [mg/l]		Bodyweight ±SD [g]			Bodyweight gain ±SD [g]
		day 1	day 8	day 15	day 1-8	day 1-15
0.23	male	219.4±3.8	254.8±3.4	291.5±4.8	35.8±3.4	72.5±3.1
	female	208.4±8.6	216.0±6.5	227.6±8.3	7.6±6.3	19.2±7.8
0.83	male	191.8±4.8	206.5±20.9	262.3±17.6	14.3±25.7	70.0±22.1
	female	191.6±3.6	196.0±8.9	220.5±6.5	4.0±10.5	28.5±8.8
1.78	male	215.0±4.2	194.0±11.3	243.5±20.5	-23.0±18.4	26.5±27.6
	female	196.2±3.6	196.0±0.0	214.0±0.0	-1.0±0.0	17.0±0.0
5.06	male	198.8±5.8	-	-	-	-
	female	192.0±6.3	-	-	-	-

Table 2: Cumulative particle size distribution (2 measurements per exposure group) of the acute inhalation toxicity study.

Particle size [µm]	Dose [mg/l]
	0.23		0.83		1.78		5.06
	1st	2nd	1st	2nd	1st	2nd	1st	2nd
<0.6	22.4	19.56	16.56	17.53	10.26	13.37	5.34	13.74
0.6-0.8	47.4	46.37	44.58	49.13	32.22	35.46	19.96	39.62
0.8-1.5	76.95	79.18	83.13	85.35	70.88	76.16	55.73	80.51
1.5-3.0	100	100	100	100	98.33	100	91.50	95.53
3.0-4.8	-	-	-	-	100	-	97.03	96.81
4.8-7.0	-	-	-	-	-	-	99.40	97.77
7.0-10.3	-	-	-	-	-	-	100	100

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute inhalation toxicity study conducted according to OECD 403 and in compliance with GLP, a LD50 of 1.1 and 1.18 mg/l (aerosol) was observed in male and female Wistar rats. The MMAD was 0.9-1.4 µm with a GSD of 1.6-2.2 µm with 97% of the particles having a diameter smaller than 5 µm. Mortality was observed in all exposure groups. 1/5 males was found dead in the 0.23 mg/l group. 1/5 males and females, each died in the 0.82 mg/l group. 3/5 males and 4/5 females animals were found dead in the 1.78 mg/l exposure group. In the high dose group all animals died. Clinical signs as panting, irregular respiration, coat bristling, uncoordinated gait, nasal discharge (blood coloured) were observed in all dose groups, mainly at the day of exposure and the day thereafter. Slightly reduced body weight gain was observed in the week after dosing with a dose-response relationship. Animals that died showed some abnormalities of the lung (red coloured lungs, emission of foam on dissection (males), plethoric (males), patchy dark red). Animals that survived until the end of the study showed no abnormalities.