Registration Dossier

Administrative data

Description of key information

Oral (OECD 423, GLP, RL1), rat: LD 50 > 2000 mg/kg bw 
Inhalation (OECD 403, GLP, RL1), rat: LC50 > 11 200 mg/l
Dermal: No data available (data waiving according to Column 2 of REACH Annex VIII, Section 8.5.2)

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
Study period:
07 April 1998 to 21 May 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(1996)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(1996)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
FEDERAL DEOARTMENT OF THE INTERIOR, Bern (Switzerland)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: HanIbm: WIST (SPF)
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 8 weeks (males) and 10 weeks (females)
- Weight at study initiation: 206-216 g (males), 171-190 g (females)
- Fasting period before study: 17.5-19.5 hours prior to treatment, and 3.5 hours after treatment
- Housing: Groups of 3 in Makrolon type-4 cages with standard softwood bedding ("Lingocel", Schill AG, CH-4132 Muttenz)
- Diet: Pelleted standard Kliba 3433, batch nos 94/97 and 20/98 rat maintanance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) ad libitum. Results of analyses for contaminants are archived at RCC.
- Water: Community tap water ad libitum. Results of bacteriological, chemical, and contaminant analyses are archived at RCC.
- Acclimation period: one week under laboratory conditions, after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 40-66
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (Music was played during the light period.)
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: The test article was readily soluble in corn oil.

MAXIMUM DOSE VOLUME APPLIED: 10 ml

DOSAGE PREPARATION: The preperation was made shortly before dosage as a weight by volume preparation. Homogeneity of the test article in the vehicle was maintained during treatment.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit-dose
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Four times during test day 1 and once daily during days 2-15
- Frequency of weighing: On test day 1 (pre-administration), 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was used as no deaths occured.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
The body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute oral toxicity according to the OECD TG 423 and in complinance with GLP. No deaths occurred and no signs of toxicity were observed. The LD50 for both males and females was found to be > 2000 mg/kg bw. Hence, classification according to 67/584/EEC and EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The test was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Jan 1986 to 13 Feb 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Wistar Hoe: WISKf(SPF71)
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Males: 207-225 g; Females: 170-181 g.
- Housing: In groups of five animals in Makrolon Type IV cages.
- Diet: Rat diet Altromin 1324 (Altromin-GmbH, Lage/Lippe) ad libitum
- Water: tap water ad libitum
- Acclimation period: Minimum of five days


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

IN-LIFE DATES: From: 30 Jan 1986 to: 13 Feb 1986
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Individual exposure chambers for nose-only exposure
- Exposure chamber volume: 60 l
- Source and rate of air: Air was supplied by using a compressor at 4 bar, and airflow was constantly adjusted at 800 l/h by using a rotameter.
- Method of conditioning air: Humidified air (100 l/h perfusing a gas wash bottle filled with water) was introduced into the inhalation chamber
- System of generating particulates/aerosols: The test item was injected into the airflow at a constant rate by using a continous infusion apparatus. The primary aerosol generation took place in a 10 l four-neck round-bottom flask. The secondary aerosol (smaller aerosol particulates) finally reached the inhalation chamber via a standpipe.
- Method of particle size determination: The aerodynamic diameter was determined by using the APS 33 Aerodynamik Particle Sizer (TSI Inc., St Paul). Analyses were conducted every 30 min, and hourly the data was saved. At the end of exposure the collected data was statistically evaluated and mean values and standard deviations were determined for 4 time points.
- Treatment of exhaust air: Trapped and neutralised.


TEST ATMOSPHERE
- Brief description of analytical method used: Samples of the aerosol were absorbed in acetone in 3 cascaded gas wash bottles and gas chromatographically analysed.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): The aerodynamic diameter was found to be in the range of 0.486 to > 15.4 µm
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gas chromatography
Duration of exposure:
ca. 4 h
Concentrations:
11.2 mg/l
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the exposure period the behaviour of the animals was closely monitored. Then animals were observed twice daily for clinical effects. Animals were weighed post-exposure on days 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 11.2 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred during the observation period.
Clinical signs:
other: - irregular, fitfully and noisy breathing - gasping - salivation - long legged, uncoordinated- and staggering tread - prone position - retracted stomach flanks - sluggished or vanished corneal reflex and positional reflex and paw flick latency; - anaesth
Body weight:
Body weight was not effected by the treatment
Gross pathology:
Necropsy revealed no pathological findings.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute inhalation toxicity according to the OECD TG 403 and in compliance with GLP. No deaths occurred and clinical signs noted were reversible within 4 days post exposure. The LC50 for both males and females was found to be > 11.2 mg/l. Hence, classification according to 67/584/EEC and EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
11 200 mg/m³
Quality of whole database:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

In the available key study the test item (≥ 95% pure) was tested according to OECD TG 423 and in compliance with GLP (RCC, 1998a). 3 Wistar rats per sex received the test material in corn oil at a dose of 2000 mg/kg bw via gavage. No deaths occurred and no signs of toxicity were observed. Macroscopic evaluation revealed no abnormal findings. The LD50 for both males and females was found to be > 2000 mg/kg bw.

This result was further supported by a second oral toxicity study. The test item (91.5% pure) was tested according to OECD TG 423 and in compliance with GLP (LPT, 2002a). 3 Crl:CD rats of both sexes received the unchanged test material via gavage. No deaths occurred and no signs of toxicity were observed. Macroscopic evaluation revealed no abnormal findings. The LD50 for both males and females was found to be > 2000 mg/kg bw.

Acute toxicity: dermal

No data available. In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the dermal route (required in Section 8.5.2 of REACH Annex VIII) does not need to be conducted as reliable data via the oral and inhalation routes are available.

Acute toxicity: inhalation

In the available key study the test item (no data on purity) was tested according to OECD TG 403 and in compliance with GLP (Hoechst, 1986a). 5 Hoe:WISKf(SPF71) Wistar rats of both sexes were exposed to the test material via inhalation (aerosol) in a nose-only inhalation chamber for 4 hours. No deaths occurred and the clinical signs noted (irregular, fitfully and noisy breathing; gasping; salivation; long legged, uncoordinated- and staggering tread; prone position; retracted stomach flanks; sluggished or vanished corneal reflex and positional reflex and paw flick latency; anaesthesia; sneezing) were reversible within 4 days post exposure. Macroscopic evaluation revealed no abnormal findings. The LC50 for both males and females was found to be > 11 200 mg/l.

Justification for classification or non-classification

The available data on acute oral and inhalation toxicity of trimethoxy(2,4,4-trimethylpentyl)silane do not meet the criteria for classification according to Regulation 1272/2008 or EU Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.