Reaction mass of 2-{[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and 2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-[2-(benzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-benzyl-2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-benzyl-N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-03-04 to 1993-06-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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:

Reaction mass of 2-{[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and 2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-[2-(benzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-benzyl-2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-benzyl-N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride.

Molecular formula:

Not applicable

IUPAC Name:

Reaction mass of 2-{[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and 2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-[2-(benzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride and N-benzyl-2-{benzyl[3-(trimethoxysilyl)propyl]amino}ethanaminium chloride and N-benzyl-N-[2-(dibenzylamino)ethyl]-3-(trimethoxysilyl)propan-1-aminium chloride.

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approximately 7-12 weeks
- Weight at study initiation: males: 153-283 g, females: 134-233 g
- Fasting period before study: 18-25 hours prior to and 3-4 hours after dosing
- Housing: The animals were housed under stadard laboratory conditions. The animals were housed in groups of 5 per sex to a cage, using labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Someren, The Netherlands). Certificates of sawdust analysis were examined and then retained in the RCC NOTOX archives. The animals were identified by earmarks.
- Diet (ad libitum): standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland). Certificates of analysis were examined and then retained in the RCC NOTOX archives.
- Water (ad libitum): tap-water. Certificates of analysis (performed quaterly) were examined and then retained in the RCC NOTOX archives.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (fluctuations were noted, but were not considered to be relevant)
- Humidity (%): 55 (fluctuations were noted, but were not considered to be relevant)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

paraffin oil

Details on oral exposure:

VEHICLE
- Specific gravity: 0.8

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION
The prepared test substance was used within 80 minutes or 18 hours after preparation and the formulation was dosed within one hour after mixing. The prepared test substance was weighed into a dry glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity of the vehicle. Homogeneity of the test substance was obtained by shaking and using a magnetic stirrer. Concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.

Doses:

Group 1: 750 mg/kg bw
Group 2: 1250 mg/kg bw
Group 3: 1650 mg/kg bw
Group 4: 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations (mortality/viability): twice daily. The time of death was recorded as precisely as possible.
- Frequency of weighing: days 1 (pre-administration), 8, 15, and at death (if found dead after day 1)
- Frequency of observations (clinical signs): at periodic intervals on the day of dosing (day 1) and once daily thereafter. The time of onset, degree, and duration were recorded.
- Necropsy of survivors performed: yes (sacrifice by oxygen/carbon dioxide asphyxiation)

Statistics:

No LD50 could be calculated due to mortality distribution.

Results and discussion

Preliminary study:

Initially a "Limit study" with the test material in paraffin oil at a dose level of 2000 mg/kg bw was performed. Due to the fact that all animals died, a "Pilot Study" was conducted in which three groups, each comprising of 1 male and 1 female rat were orally dosed with the test substance in paraffin oil at 50, 100, or 650 mg/kg bw. None of these animals died, only rough coat was observed in some animals. Therefore, two lower dose levels were selected for the full study and animals dosed at 1250 or 750 mg/kg bw. Due to the fact that no animals died, a fourth group was added and animals dosed at 1650 mg/kg bw. All animals receiving 1650 mg/kg bw died. No further groups were selected as a clear dose level at which animals died and at which animals survived (all within one classification group) was obtained.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

1 250 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD100

Effect level:

1 650 mg/kg bw

Based on:

test mat.

Mortality:

In groups 1 and 2 (750 and 1250 mg/kg bw) none of the animals (neither male nor female) died. In groups 3 and 4 (1650 and 2000 mg/kg bw) all animals (both males and females) died within 24 hours of dosing.

Clinical signs:

other: Group 1 (750 mg/kg bw): rough coat (1 male on day 10 only) Group 2 (1250 mg/kg bw): salivation (1 female on day 1 only) Group 3 (1650 mg/kg bw): no clinical signs observed Group 4 (2000 mg/kg bw): lethargy, clonic spasms, hunched posture, rough coat, wate

Gross pathology:

Group 1 (750 mg/kg bw): no abnormalities that were not commonly noted among rats of this strain and age
Group 2 (1250 mg/kg bw): no abnormalities that were not commonly noted among rats of this strain and age
Group 3 (1650 mg/kg bw): dark red focus/foci in the glandular stomach, haemorrhages in the wall of the duodenum, jejenum, and ileum, haemorrhages in the thymus
Group 4 (2000 mg/kg bw): dark red focus/foci in the glandular stomach, haemorrhages in the thymus, alopecia in the cervical region

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS Category 4 (H302) according to Regulation (EC) No 1272/2008

Conclusions:

The test item was tested for acute oral toxicity according to the OECD TG 401 (1987) and in compliance with GLP. The test item was found to be harmful as the experiment resulted in 1250 mg/kg bw < LD50 < 1650 mg/kg bw for both male and female rats. Hence, the substance has to be classified as acute oral toxicity Cat 4 according to EC/1272/2008.