Triethoxypropylsilane

Endpoint summary

Description of key information

Oral (OECD TG 401), rat: LD50 > 5110 mg/kg bw.
No measured acute inhalation data are available for the registered substance, triethoxypropylsilane, however reliable data are available for the structural analogue substance trimethoxypropylsilane (CAS 1067-25-0)
Inhalation (OECD TG 403), rat: 4 h: LC50 > 22200 mg/m³.
No measured data are available for the dermal route (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:

01-10-1991 to 08-10-1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

dose volume exceeded

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen.
- Age at study initiation: 8 weeks (males) and 9 weeks (females)
- Weight at study initiation: 147-165 g (males) and 132-142 g (females)
- Fasting period before study: Approx. 16 hours before treatment
- Housing: Macrolon cages, type II. One animal per cage. Animal bedding chips, supplied by Jelu-Werk, J. Ehrler, Industriemehule, D-7092 Rosenberg/Württ.
- Diet: Standard diet ad libitum, ssniff R, Special diet for rats.
- Water: Water was provided ad libitum in drinking water quality from Stadtwerke Bielefeld, using an automatic drinking water system with drinking nipples.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 – 22.5
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 01-10-1991 To: 15-10-1991

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 237 mg/mL
- Justification for choice of vehicle: substance is insoluble in water.
- Lot/batch no. (if required): 8249


MAXIMUM DOSE VOLUME APPLIED: 21.5 mL/kg (guideline: <= 1 mL/100 g bw)

DOSAGE PREPARATION (if unusual): prepared as emulsion before dosing

Doses:

5110 mg/kg bw

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: The animals were continuously observed for first 4 to 6 hours after administration and then once daily. The nature of the toxicity as well as the onset, the intensity, and the duration of the signs were recorded. Mortality was checked twice daily (a.m. and p.m.), on weekends only once. The body weights were recorded at the beginning and also 7 and 14 days after administration
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, body orifices, body cavities (thoracic and abdominal), and their content.

Statistics:

None given.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 110 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Signs of toxicity were restrained gait, slight to moderate clonic convulsions, slight to moderate mydriasis, and diarrhea in male and female rats. In additions , male animals showed slight hypokinesia, chromoacryorrhea, and piloerection. In one female ani

Gross pathology:

Necropsy and histopathological examinations revealed no substance-related findings

Table 2. Body weights (g) – Individual Values.

Dose (mg/kg bw)	Animal No.	Day 0	Day 7	Day 14
Male animals
5110	1	165	224	243
	2	154	215	237
	3	147	202	227
	4	149	201	224
	5	152	203	226
Female animals
5110	6	142	160	162
	7	136	173	171
	8	136	160	159
	9	135	174	173
	10	132	148	149

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In an acute oral toxicity study conducted in rats according to the now deleted OECD 401 and in compliance with GLP, the LD50 for triethoxypropylsilane was greater than 5110 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 110 mg/kg bw

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 VII, 8.5, 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Deviations unlikely significantly to affect the outcome of the study: excursions from recommended relative humidity and temperature; limited reporting of clinical observations.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Wistar derived Crl:WI(WU)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, GERMANY
- Age at study initiation: 7 weeks
- Weight at study initiation: mean - 218 g (males), 166 g (females)
- Fasting period before study: none stated
- Housing: (after exposure) 5 males or 5 females per suspended stainless steel cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): during exposure: mean 22.6; after exposure: 22 +/-3 (excursion 18.5 for 1 h)
- Humidity (%): during exposure: mean 79 +/-15 (excursion >70% for 2 h); after exposure: 30-70 (excursions 29, 74, 95 for 1 h on each occasion)
- Air changes (per hr): during exposure: 38; after exposure: 10
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1990-02-07 To: 1990-02-21

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: horizontal glass chamber; animals separated by perforated stainless steel plates
- Exposure chamber volume: 16 L (total volume)
- Method of holding animals in test chamber: see above
- Source and rate of air: 0.6 m³/h; flow velocity 34 m/h; ventilation frequency 38/h
- System of generating particulates/aerosols: heated air bubbled through heated test material at 35° C, passed through heated Pall filter (30 °C) to remove aerosol as far as possible
- Method of particle size determination: to determine aerosol content: 11-stage cascade impactor
- Treatment of exhaust air: no details
- Temperature, humidity, pressure in air chamber: (mean of hourly measurements) 22.6 deg C; 79 +/-15%; pressure unstated

TEST ATMOSPHERE
- Brief description of analytical method used: hourly GC analysis
- Samples taken from breathing zone: yes

TEST ATMOSPHERE: 22.2+/-6.9 g/m³ (4 measurements); nominal 59.8 g/m³; particle size tabulated, about 1% of the total test atmosphere consisted of aerosol.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Single exposure concentration:
22.9 +/-6.9 g/m³ (measured)
59.8 g/m³ (nominal)

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: observations daily; body weights prior to exposure and on observation days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

None relating to LC50.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22 200 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

One of each sex died during exposure. One male died on observation day 4.

Clinical signs:

other: irregular breathing, narcosis shortly after exposure (see under "any other information o nresults" for more details

Body weight:

Body weights were reduced in two females on days 14, or 7 and 14.

Gross pathology:

The lungs of the three animals that died during treatment or observation were discoloured red, spotted or swollen. No abnormalities were found in the remaining animals autopsied on day 14.

Table 1: Concentrations, exposure conditions and mortality per animals treated

Nominal Conc. (g/m^3)	Analytical Conc. (g/m^3)	Mortality (dead/total)
		Males	Females	Combined
59.8	22.2 +/- 6.9	2/5	1/5	3/10

 

Clinical signs: Shortly after exposure, restlessness and irregular breathing was observed followed by narcosis and deep and irregular breathing. Wet noses and dirty fur were common observations on the first day of the observation period, but there were no abnormalities thereafter. Just before death the male demonstrated lethargy, showed flabby muscles, incoordination, piloerection and a visually increased breathing frequency. These findings are reported as narative - full tabulated details are not presented.

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In an acute inhalation study according to OECD 403 and in accordance with GLP (reliability score 1) the LC50 for the structural analogue substance trimethoxypropylsilane (CAS: 1067-25-0) was in excess of 22200 mg/m³ in the rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 22 200 mg/m³ air

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment

 

The key acute oral toxicity study which was conducted in compliance with GLP and according to the now deleted OECD TG 401, reports an LD₅₀value of > 5110 mg/kg bw/d after single oral administration of the registered substance. Both sexes showed restrained or stilted gait (10/10), clonic convulsions (10/10), mydriasis (2/5m, 5/5f) and diahorrea (2/5m, 1/5f). Males exhibited slight hypokinesia (2/5m), chromodacryorrhea (1/5m) and piloerection (2/5m). Symptoms were observed between 35 minutes and three days after administration (ASTA Medica, 1992a).

 

No measured acute inhalation data are available for the registered substance, triethoxypropylsilane, however data are available for the structural analogue substance trimethoxypropylsilane (CAS: 1067-25-0). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of tritethoxypropylsilane. Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

 

The key acute inhalation toxicity study which was conducted in compliance with GLP and according to OECD TG 403 is available for the structural analogue substance trimethoxypropylsilane and which reports an LC₅₀ value of > 22200mg/m³ in rats. Shortly after exposure, restlessness and irregular breathing was observed followed by narcosis and deep and irregular breathing. Wet noses and dirty fur were common observations on the first day of the observation period, but there were no abnormalities thereafter. Just before death the male demonstrated lethargy, showed flabby muscles, incoordination, piloerection and a visually increased breathing frequency (TNO, 1990). The LC₅₀ for the target chemical is also considered to be 22200 mg/m³.        

 

No measured data are available for the dermal route.

Justification for classification or non-classification

The available data on acute oral and inhalation toxicity (lethality) of the registered substance and the structural analogue substance, trimethoxypropylsilane (CAS 1067 -25 -0), respectively, do not meet the criteria for classification according to Regulation (EC) 1272/2008 , and are therefore conclusive but sufficient for classification of the registered substance.

Classification as STOT-SE Cat 3, with the hazard statement 'H336: May cause drowsiness and dizziness' according to Regulation (EC) 1272/2008 is not warranted for the test substance. Although signs of narcosis were observed in the acute inhalation study, this was rather linked to the systemic effects provoked by the test substance after exposure at a concentration exceeding the limit dose stated in the corresponding OECD guideline. In addition the reported concentration could have been higher due to the whole-body inhalation and possible additional oral uptake of the test substance. Mortality and clinical signs as laboured breathing and lethargy were observed. At necropsy dark red discoloured lungs were reported, thus leading to the conclusion that the narcotic effects were rather a consequence of anoxia provoked by systemic effects.