N,N-dimethyl-3-(trimethoxysilyl)propylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyl-3-(trimethoxysilyl)propylamine

EC Number:

219-786-3

EC Name:

N,N-dimethyl-3-(trimethoxysilyl)propylamine

Cas Number:

2530-86-1

Molecular formula:

C8H21NO3Si

IUPAC Name:

dimethyl[3-(trimethoxysilyl)propyl]amine

Test material form:

liquid

Details on test material:

- Name (as cited in the report): SAT 170001
- Chemical Name: N,N-dimethyl-3-(trimethoxysilyl)propylamine
- CAS No.: 2530-86-1
- Batch No.: 186020160504
- Aggregate State at RT: liquid
- Colour: colourless
- Storage Conditions: room temperature
- Expiry Date: 30.08.2017

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

ANIMALS
- Species/strain: WISTAR rats Crl: WI(Han)
- Source: Charles River, Germany
- Sex: female (non-pregnant, nulliparous)
- Number of animals: 3 per step
- Age at the beginning of the study: 8 - 10 weeks
- Body weight on the day of administration: Step 1: 142 – 155 g / Step 2: 154 – 166 g / Step 3: 178 – 197 g
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare the animals were bred for experimental purposes. This study was performed in an AAALAC-accredited laboratory. According to German animal protection law, the study type has been reviewed and accepted by local authorities. Furthermore, the study has been subjected to Ethical Review Process and was authorised by the Bavarian animal welfare administration.

HOUSING & FEEDING
- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions
The animals were marked for individual identification by tail painting. Prior to the administration a detailed clinical observation was made of all animals. Only healthy
animals were used. Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

300 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

It is the principle of the acute toxic class method that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test item to enable its classification. The item is tested using a stepwise procedure with up to four fixed doses. Absence or presence of compound-related mortality of the animals dosed at one step will determine the next step.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

< 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off

Mortality:

No mortality

Clinical signs:

other: The test item showed acute oral toxicity characteristics after a single dose administration at a dosage of 2000 mg/kg bw.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Any other information on results incl. tables

CLINICAL SIGNS PER STEP

STEP 1: 300 mg/kg bw, 3 females

0 min - 15 d

nsf

STEP 2: 2000 mg/kg bw, 3 females

0 - 30 min	nsf
30 - 180 min	Slightly reduced spontaneous activity
180 min - 2 d	nsf
2 d - 3 d	Slight piloerection (1/3 rats)
3 d - 15 d	nsf

STEP 3: 2000 mg/kg bw, 3 females

0 - 30 min	Slightly reduced spontaneous activity, hunched posture, slight piloerection, half eyelid closure (2/3 rats), prone position (1/3 rats)
30 - 60 min	Moderately reduced spontaneous activity, hunched posture, slight piloerection, half eyelid closure
60 - 120 min	Slightly reduced spontaneous activity, half eyelid closure
120 - 180 min	Slightly reduced spontaneous activity, slight piloerection
180 - 240 min	Slightly reduced spontaneous activity
240 min - 15 d	nsf

LD50 CUT-OFF

Dose [mg/kg bw]	No. of animals	No. of intercurrent deaths	LD50 Cut-Off
300	3	0	5000 mg/kg bw
2000	6	0

nsf: no specific findings

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 300 mg/kg body weight was not associated with signs of toxicity or mortality.
Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but not with mortality. The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 5000 mg/ kg bw.
According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for toxicity and is not classified.
According to GHS (Globally Harmonized Classification System) the test item has no obligatory labelling requirement for toxicity and is classified into Category 5.

Executive summary:

One group, of three female WISTAR Crl: WI(Han) rats, was treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was dissolved in olive oil at a concentration of 0.03 g/mL and administered at a dose volume of 10 mL/kg.

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved in olive oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

RESULTS

All animals treated with the test item at a dose of 300 mg/kg bw (step 1) survived until the end of the study without showing signs of toxicity.

All animals treated with the test item at a dose of 2000 mg/kg bw (step 2 and 3) survived until the end of the study showing signs of toxicity.

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, half eyelid-closure, hunched posture and prone position. All symptoms recovered within up to 2 days post-dose.

Throughout the 14-day observation period, the weight gain of all animals was within the normal range of variation for this strain.

At necropsy, no macroscopic findings were observed in any animal of any step.

CONCLUSION

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 300 mg/kg body weight was not associated with signs of toxicity or mortality.

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but not with mortality. The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 5000 mg/ kg bw.

According to Annex I of Regulation (EC) 1272/2008 the test item has no obligatory labelling requirement for toxicity and is not classified.

According to GHS (Globally Harmonized Classification System) the test item has no obligatory labelling requirement for toxicity and is classified into Category 5.