Trimethoxy(2,4,4-trimethylpentyl)silane

Endpoint summary

Description of key information

Oral (OECD 423, GLP, RL1), rat: LD50 > 2000 mg/kg bw 
Inhalation (OECD 403, GLP, RL1), rat: LC50 > 11.2 mg/L (maximum attainable concentration)
Dermal: No data available (data waiving according to Column 2 of REACH Annex VIII, Section 8.5.3)

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 - 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 DEPARTMENT 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., 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 ("Lignocel", Schill AG, Switzerland)
- Diet: Pelleted standard Kliba 3433, batch nos 94/97 and 20/98 rat maintanance diet (Kliba Mühlen AG, Switzerland) 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/kg bw

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.

Doses:

2000 mg/kg bw (step 1 and 2)

No. of animals per sex per dose:

step 1: 3 males
step 2: 3 females

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 occurred.

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:

other: No clinical signs of toxicity were observed during the study period.

Body weight:

other body weight observations

Remarks:

The body weight 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 Regulation (EC) No. 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 available information comprises adequate, reliable (Klimisch score 1) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5.1, of Regulation (EC) No 1907/2006.

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 - 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, Germany
- 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, Germany) 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 (maximum technically attainable concentration)

No. of animals per sex per dose:

5

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

Remarks on result:

other: maximum attainable concentration

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 Regulation (EC) No. 1272/2008 is not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 11.2 mg/L air

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5.2, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

In the available key study trimethoxy(2,4,4 -trimethylpentyl)silane (>=95% pure) was tested according to OECD TG 423 and in compliance with GLP (RCC, 1998). 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, 2002). 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 8.5.3 of REACH Annex VIII) does not need to be conducted as the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure.

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, 1986). 5 Hoe:WISKf(SPF71) Wistar rats of both sexes were exposed to the test material at the maximum technically attainable concentration 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 > 11.2 mg/L.

Justification for classification or non-classification

The available data on acute toxicity of trimethoxy(2,4,4-trimethylpentyl)silane do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.