N-butyl-N-[(triethoxysilyl)methyl]butan-1-amine

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 per step
Age at the
beginning of the study: 8-12 weeks old
Report, BSL BIOSERVICE Study No.143950 page 15 of 26
Version: Final
Body weight on the
day of administration: Step 1: animals no.: 1 - 3: 166 - 171 g
Step 2: animals no.: 4 - 6: 155 - 164 g
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare the animals were bred for experimental purposes.

Preparation of the Animals:
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.

ENVIRONMENTAL CONDITIONS
- 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 (lot no. 1526)
- 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 (lot no. 02102140509)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 g of the test item were suspended with the vehicle to gain a final volume of 10 mL
- Amount of vehicle (if gavage): The test item was administered at a dose volume of 10 mL/kg body weight.
- Justification for choice of vehicle: Cotton seed oil was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): (Sigma-Aldrich, lot no. MKBN8713V, expiry date: 30 September 2014)

Doses:

The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.

No. of animals per sex per dose:

Number of animals: 3 per step

Control animals:

no

Details on study design:

- Observation Period
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

- Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

- Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

- Pathology
The animal which had to be sacrificed for ethical reasons during the observation period was necropsied as soon as it was killed. At the end of the observation period the all animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no.: 236014; expiry date: 31 January 2014) at a dosage of 250-400 mg/kg bw. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000

Based on:

test mat.

Remarks on result:

other: A dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

Mortality:

Under the conditions of the present study, a single oral application of the test item N,N-Dibutylaminomethyl-triethoxysilan to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

Clinical signs:

No specific findings.

Body weight:

None of the animals showed weight loss during the observation period.

Gross pathology:

No specific findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, a single oral application of the test item N,N-Dibutylaminomethyl-triethoxysilan to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

The median lethal dose of N,N-Dibutylaminomethyl-triethoxysilan after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): unclassified
In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item
N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for toxicity and is not classified.
According to GHS (Globally Harmonized Classification System) the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for toxicity and is not classified.

Executive summary:

SUMMARY RESULTS

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 suspended with the vehicle cotton seed 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 after their entrance at BSL 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.

All animals survived until the end of the study without showing any test-item related signs of toxicity.

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

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

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC, the substance should be: not classified

On the basis of the test results given below and in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008, the substance should be: not classified

Conclusion:

Under the conditions of the present study, a single oral application of the test item N,N-Dibutylaminomethyl-triethoxysilan to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.

The median lethal dose of N,N-Dibutylaminomethyl-triethoxysilan after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): unclassified

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item

N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for toxicity.

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

According to GHS (Globally Harmonized Classification System) the test item N,N-Dibutylaminomethyl-triethoxysilan has no obligatory labelling requirement for toxicity and is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.6, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute toxicity test according the acute toxic class method (OECD 423) with N,N-Dibutylaminomethyl-triethoxysilane was performed. In the first step the test item was given at a dose of 2000 mg/kg bw to a group of 3 female rats (WISTAR rats Crl: WI(Han)) in a single exposure via oral gavage. In the second step the test item was given at the same dose to a further group of 3 female rats (WISTAR rats Crl: WI(Han)) in a single exposure via oral gavage. All animals survived until the end of the study without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Therefore, the LD50 (oral, rat) was determined to be > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Key Study

Justification for classification or non-classification

The LD50 (oral, rat) was determined to be > 2000 mg/kg bw. to rats, without showing any test-item related signs of toxicity or mortality. The product is not classified for acute toxicity.