N-[3-(trimethoxysilyl)propylcyclohexylamine]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Aug - 08 Oct 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

(1984)

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-(trimethoxysilyl)propylcyclohexylamine]

EC Number:

221-329-8

EC Name:

N-[3-(trimethoxysilyl)propylcyclohexylamine]

Cas Number:

3068-78-8

Molecular formula:

C12H27NO3Si

IUPAC Name:

N-[3-(trimethoxysilyl)propyl]cyclohexanamine

Details on test material:

- Name of test material (as cited in study report): Wacker Silan GF 92
- Physical state: yellowish fluid
- Expiration date of the lot/batch: 29 Apr 1992
- Storage condition of test material: at 4 °C in a refrigerator

Test animals

Species:

rat

Strain:

other: Hoe:WISKf(SPF71)

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: 198 - 212 g (males), 186 - 212 g (females)
- Housing: animals were housed in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals.
- Diet: rodent diet Altromin 1324 (Altromin-GmbH, Lage, Germany), ad libitum
- 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/head 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 hold in cylindrical plastic cages and are exposed to a defined aerosol concentration via nose only inhalation.
- Source and rate of air: filtered air at 0.8 m³/h
- System of generating aerosols: the test material was injected in a nozzle via permanent infusion device with a constant rate. Primary aerosol formation occurred in a glass flask. Smaller aerosol particles (secondary aerosol) were piped in the exposure chamber via a standpipe.
- Method of particle size determination: Anderson-Kaskadenimpaktor Mark III followed by Probit analysis
- Treatment of exhaust air: exhausted air/aerosol is removed and filtered via a methanol, water and cotton wool wash bottle followed by a buehlerfilter and a calciumchloride wash bottle.
- Temperature and humidity in air chamber: 21.1 - 22.9 °C, 13.2 - 34.7%

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric measurements were performed for determination of test material concentration (15 min interval).
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle: filtered clean air
- Concentration of test material in vehicle: 1.59, 1.65, 0.89, 3.17 mg/L

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.7 - 1.1 / 1.6 - 1.9

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The test substance was absorbed in gas washing bottles. The samples were diluted in n-hexane. The determination of the test substance was performed by gaschromatography using an FID as detector.

Duration of exposure:

4 h

Concentrations:

Group 1: 1.59 mg/L air (nominal concentration)
Group 2: 1.65 mg/L air (nominal concentration)
Group 3: 0.89 mg/L air (nominal concentration)
Group 4: 3.17 mg/L air (nominal concentration)

No. of animals per sex per dose:

5 (Group 1 - 3)
5 females (Group 4)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days (Group 1), 14 days (Group 2, 3), 28 days (group 4)
- Frequency of observations and weighing: Clinical signs were observed twice daily and once daily on weekends and public holidays. Body weights were recorded in weekly intervals.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

2.3 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

1.6 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: combined LC50 for males/females

Mortality:

5/10, 4/10, 0/10 and 3/5 animals died during the study period when exposed to 1.59, 1.65, 0.89 and 3.17 mg/L air, respectively.

Clinical signs:

other: Animals exposed with 0.89 mg/L air of the test material showed fitful and cracking breathing, ataxic/staggering movements, reddish rhinorrhea, sneezing and piloerection. Animals exposed to higher concentrations of the test material additionally showed cli

Body weight:

With the exception of one female all animals showed body weight gain until study termination.

Gross pathology:

Gross pathology of animals died during the study revealed discoloured lungs and liver, spotted lungs, inflated intestine and foam withdrawal from dissected lungs.

Any other information on results incl. tables

Table 1: Mortality data

Animals Group	Target Concentration [mg/L air]	Mortality	Clinical Signs
		N	N
Males
1	1.59	3/5	5/5
2	1.65	2/5	5/5
3	0.89	0/5	5/5
Females
1	1.59	2/5	5/5
2	1.65	2/5	5/5
3	0.89	0/5	5/5
4	3.17	3/5	5/5

N= Number of animals/number of animals used

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS Category 4 (H332) according to Regulation (EC) No 1272/2008

Conclusions:

In an acute inhalation toxicity study according to OECD guideline 403 and in compliance with GLP, a combined LC50 of 2 mg/L air was derived for male and female rats resulting in category 4 classification.