Diethoxy(methyl)silane

Endpoint summary

Description of key information

Oral (OECD 423): LD50 > 2000 mg/kg bw 
Inhalation (OECD 403): LC50 = 4731 ppm (males/females) 
Dermal (OECD 402): LD50 > 2000 mg/kg bw

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:

12 Feb - 01 Mar 2007

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:

(2001)

Deviations:

yes

Remarks:

rational for starting dose not specified

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2002)

Deviations:

yes

Remarks:

rational for starting dose not specified

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt fuer Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik, Munich, Germany

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HsdRccHan : WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen
- Weight at study initiation: step 1: 175-181 g, step 2: 185-196g
- Fasting period before study: fasting over night, and 3-4 hours post application
- Housing: in Macrolon cages on altromin saw fiber bedding
- Diet: Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF), ad libitum
- Water: drinking water (municipal residue control, microbiol. controlled periodically), ad libitum
- Acclimation period: adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Justification for choice of vehicle: Since the test substance is sensitive to hydrolysis, care was taken to avoid contact to water, as vehicle cotton seed oil was used
- Lot/batch no.: 125K0087

CLASS METHOD
- Rationale for the selection of the starting dose: not specified

Doses:

2000 mg/kg bw in step 1 and 2

No. of animals per sex per dose:

3 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing was done before application and once a week thereafter, observations were made several times on day of dosing and once a day thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortalities or clinical signs of toxicity observed

Mortality:

No mortalities were observed during the study.

Clinical signs:

other: No clinical sings were observed during the study.

Gross pathology:

Besides acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animal of any step.

Interpretation of results:

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

Conclusions:

In conclusion, under the conditions of the present study, according to OECD 423 and GLP, at the limit concentration of 2000 mg/kg bw no mortalities or clinical signs of toxicity were observed. The test substance does not need to be classified for acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was carried out in accordance with an 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:

25 Mar - 05 May 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

On April 28, 1999, the temperature and humidity of the animal room were not recorded for the Group 4 rats. A pre-exposure analytical sample of the chamber concentration prior to Group 1 animal exposure was not taken as required by the protocol.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley (Crl:CD VAF/Plus)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kalamazoo, Michigan, USA
- Weight at study initiation: 271 - 324 g (males), 195 - 227 g (females)
- Age at study initiation: 8 weeks
- Housing: Animals were individually housed in suspended, stainless steel, wire-mesh cages.
- Diet: Certified Rodent chow #5002, PMI Nutrition International, Inc., St. Louis, Missouri, USA, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: 7 – 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 – 23.3
- Humidity (%): 30 – 62
- Air changes (per hr): at least 12
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass and acrylic chamber with an acrylic antechamber
- Exposure chamber volume: 0.152 m³
- Source and rate of air: airflow was 31 L/min
- Method of conditioning air: The vapor exposure atmosphere was generated using an in-house designed vapor exposure chamber with a glass bead-column generation system. The vapor generation system operated as follows: Test article was delivered from a 50 mL gas-tight syringe through 1/8" Teflona tubing by a syringe pump at a constant rate of approximately 59 µL/min (198 ppm group) and 464 - 580 µL/min (2312 ppm group) to a chromatography column containing glass beads. For the 4731 ppm group, a digital FMI pump was used instead of a syringe pump. The FMI pump was calibrated to determine the appropriate setting for the required flow rate. Compressed air, metered by a flowmeter at approximately 15 L/min, flowed counter current, vaporizing the test article. Concentrated vapors of the test article were diluted with additional compressed air to achieve the desired concentration. The dilution air was metered with a flowmeter at the rate of 16 L/min. The test article vapor laden air stream was then delivered to the exposure chamber through a stainless steel "T" to aid chamber distribution.
- Treatment of exhaust air: Prior to the exposure, samples were taken from the animal breathing zone of the chamber to show that the test article was evenly distributed. Samples taken from the exposure chamber were analyzed during a test trial prior to the initial Group 1 animal exposure.
- Temperature, humidity, air chamber: 21 °C, 28 - 42% (test chamber)

TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- Brief description of analytical method used: A Miran infrared (IR) spectrometer monitored the chamber atmosphere for Y-1205. The IR was used to continuously monitor chamber concentrations and make real-time adjustments during the exposures. Atmosphere samples were drawn into the IR at a constant rate from the breathing zone of the animals. The IR response was displayed on a multimeter and recorded at approximately hourly intervals. Test article chamber levels were determined from a calibration curve. In addition, samples of the Y-1205 exposure atmospheres were collected hourly and analyzed using the Sponsor-supplied gas chromatography (GC) method. Samples were collected approximately once per hour during the exposures. Actual chamber concentration of Y-1205 and ethanol were determined by GC. Because ethanol is a hydrolysis product of Y-1205, GC analysis of ethanol in the chamber atmosphere provided an indication of the exposure atmosphere integrity (a stable, non-fluctuating atmosphere during exposure duration) and the test article hydrolysis. Purity analysis was conducted on the neat test article collected before each exposure to ensure purity was 92% or higher.

CLASS METHOD
- Rationale for the selection of the starting concentration: The exposure levels were selected by the Sponsor, or in consultation with the Sponsor, on the basis of available data from previous studies with structurally analogous materials.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(GC)

Duration of exposure:

4 h

Concentrations:

337, 2688 and 8091 ppm (males/females, nominal concentration)
198, 2312 and 4731 ppm (males/females, analytical concentration)
1.10, 12.90 and 26.4 mg/L (males/females, calculated analytical concentration at 20°C using a MW of 134.25 g/mol)

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: All animals received a detailed clinical examination just prior to exposure, immediately upon removal from the chamber, at 1,2, and 4 hours post-exposure, and once daily thereafter. All rats received an ophthalmoscopic examination prior to exposure and within 60 minutes post-exposure. Neurobehavioral observations were conducted once daily on days 2 - 15. Body weight measurements were measured and recorded just prior to exposure on day 1 and on days 2, 3, 5, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: All major organs in the thoracic and abdominal cavities were observed for gross abnormalities, all gross lesions were saved, and the carcasses were discarded.

Statistics:

The means and standard deviations were calculated for body weights.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

26.4 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: calculated analytical concentration using at 20°C using a MW of 134.25 g/mol

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4 731 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred in the groups exposed to 198 ppm and 2312 ppm Y-1205 vapors. The mortality for animals exposed to 4731 ppm Y-1205 vapors was 50% (2 males, 3 females).

Clinical signs:

other: Test article-related clinical signs observed during all the exposures included decreased activity and body surface staining. Signs of toxicity observed post-exposure and during the 14 day observation period for the 2312 ppm groups were hair loss, body sur

Body weight:

Group mean body weights were moderately affected by exposure to Y-1205. In general, surviving animals lost weight immediately post-exposure, then gained weight to exceed their pre-exposure weight by the end of the 14 day observation period.

Gross pathology:

There were no organ specific test article-related macroscopic observations noted in these animals. One 4731 ppm male rat that died on study was thin, indicating that the animal was not eating and simply confirming the systemic toxicity induced by the compound. Also, a single 4731 ppm female that died on study was noted to have red discoloration of the lungs. This is a common finding in animals found dead on study. Since this finding was only noted in 1 high dose animal, it is doubtful that this represents a test article-induced lesion. The small testis and epididymis noted at 4731 ppm occurred in the same male rat and only the left testis and epididymis were affected. These findings, and the pelvic dilatation in the kidney, are commonly occurring lesions in rats of this age and strain and are not considered to be test article-related.

Other findings:

No ophthalmoscopic abnormalities were observed in the rats exposed to 198 or 2312 ppm of Y-1205. The rats exposed to 4731 ppm of Y-1205 were normal prior to exposure and 9 of the 10 rats had pupillary constriction (pinpoint miosis) post-exposure.

Table 1: Mortality data

Cumulative Group Mortality data
Group	Number of animals (M/F)	Day death occurred						Cumulative Mortality
		1		4		9		Males	Females	Combined
		M	F	M	F	M	F
1	5/5	0	0	0	0	0	0	0	0	0
3	5/5	0	0	0	0	0	0	0	0	0
4	5/5	0	3	1	0	1	0	2	3	5

M= males

F= females

Group 1: 198 ppm, group 3: 2312 ppm, group 4: 4731 ppm

Interpretation of results:

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

Conclusions:

In conclusion, under the conditions of the present study conducted in manner similar to OECD 403 and GLP, the LC50 is > 26.4 mg/L for both male and female rats. The test substance does not need to be classified for acute inhalation toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Feb - 20 Feb 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:(CD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Portage, MI, USA
- Age at study initiation: Young adult
- Weight at study initiation: 228 – 282 g
- Housing: Animals were caged in individually suspended wire-mesh cages.
- Diet: Purina Certified Rodent Chow #5002, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 – 22.4
- Humidity (%): 44.9 – 53.2
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: 18 - 23
- Type of wrap if used: The test material was held in contact with the skin with gauze bandaging. The bandage was secured with nonirritating tape. Collars were applied and remained on the rats for the duration of the exposure to prevent the ingestion of the test material and/or wrappings during the 24-hour exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with disposable paper towels moistened with tepid tap water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2.38 mL/kg bw
- Concentration: 0.84 g/mL
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

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: 14 days
- Frequency of observations and weighing: Animals were observed 1, 3 and 4 h post administration of the test substance and twice daily thereafter for 14 days. Individual body weights were determined weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were observed 1, 3 and 4 h post administration of the test substance and once daily thereafter for 14 days.

Statistics:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occured during the study period.

Clinical signs:

other: Clinical findings were limited to wet or dried yellow urogenital staining for four rats and dried red material around the eye(s) and/or nose for three rats. These findings are typically noted in association with the bandage/collar application procedures a

Gross pathology:

Dilated renal pelves, distended ureter(s) and multiple calculi in the ureter(s) and urinary bladder were noted in one male rat at the terminal necropsy. These are common, spontaneous findings in rats of this age and strain and were unrelated to the test material. There were no other gross necropsy findings for all examined tissues.

Other findings:

Dermal observations:
Very slight erythema was noted on two male rats. Desquamation was present on six animals. There was no edema or other dermal findings. Erythema completely subsided by day 2. All dermal irritation completely subsided by day 14 or earlier.

Interpretation of results:

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

Conclusions:

In conclusion, under the conditions of the present study, according to OECD 402 and GLP, the LD50 is > 2000 mg/kg bw for both male and female rats. The test substance does not need to be classified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP.

Additional information

Acute oral toxicity

Three acute oral toxicity studies with diethoxy(methyl)silane (CAS 2031-62-1) are available

In the key acute oral toxicity study with CAS 2031-62-1 performed according to OECD TG 423 as a limit test and in compliance with GLP six fasted female Wistar rats were administered a single dose of 2000 mg/kg bw via oral gavage (BSL, 2007). The animals were observed for 14 days after administration. The acute oral LD50 value was calculated to be greater than 2000 mg/kg bw. No signs of clinical toxicity were reported, no mortalities occurred during the observation period. All animals showed the expected body weight gains over the study period.

In one supporting acute oral toxicity study performed according to OECD TG 401 and in compliance with GLP the test material (CAS 2031-62-1) was administered via oral gavage to 5 male and 5 female Albino rats each dose group 3864, 5000 and 6500 mg/kg bw. The animals were observed for 14 days after administration. The LD50 values were calculated to be 5832 and > 6500 mg/kg bw for females and males, respectively. The combined LD50 value for females/males was calculated to be 6121 mg/kg bw. All deaths occurred within two days after dosing. There were 01/10, 4/10 and 5/10 deaths at 3846, 5000 and 6500 mg/kg bw, respectively. Clinical findings were noted in all dose groups including ataxia hypoactivity, wet staining, labored respiration, clear ocular discharge and prostration. A single female animal had hypothermia (body cool to touch). There were no other clinical findings. All surviving animals appeared normal by day 5 or earlier and throughout the remainder of the study. No remarkable changes or differences in body weights were reported during the study period. Gross necropsy revealed dark red contents, dark red area(s), reddened mucosa and/or gas-filled, distended portions in the stomach and/or intestine were noted for all rats that were found dead. Eight rats that died during the study had dark red and/or white area(s) on the liver. Reddened pancreases were observed for four animals that did not survive to the scheduled euthanization. Single animals that died had reddened adrenal glands, reddened lymph nodes and pale lungs. There were no other gross necropsy findings for all other animals that were found dead.

 

In another supporting acute oral toxicity study performed according to OECD TG 401 and in compliance with GLP five fasted male and female Wistar rats were administered one dose of 5000 mg/kg bw of diethoxy(methyl)silane (CAS 2031-62-1) via oral gavage (TNO, 1986). The animals were observed for 14 days after administration. The acute oral LD50 value was calculated to be greater than 5000 mg/kg bw. No mortality occurred during the observation period. Within one hour after treatment the rats showed sluggishness and signs of ataxia. These phenomena had disappeared after 24 hours. No further clinical signs of toxicity were reported during the study period. All animals showed the expected body weight gains over the study period. Based on the above study results and according to EU classification criteria, the test substance is not to be classified.

Acute inhalation toxicity

A key acute inhalation toxicity study performed according to OECD TG 403 and in compliance with GLP with diethoxy(methyl)silane (CAS 2031-62-1) is available (MPI, 2000). Five Wistar rats of each sex per dose were exposed to a vapour of the test item in a whole body exposure chamber for 4 hours at concentrations of 198, 2312 and 4731 ppm (analytical concentration). The animals were observed for 14 days after administration. The LC50 value was calculated to be 4731 ppm for males/females. No mortalities occurred in the groups exposed to 198 and 2312 ppm vapours. The mortality for animals exposed to 4731 ppm vapors was 50% (2 males, 3 females). Test article-related clinical signs observed during all the exposures included decreased activity and body surface staining. Signs of toxicity observed post-exposure and during the 14-day observation period for the 2312 ppm groups were hair loss, body surface staining, and red/brown material around the nose. Animals in the 198 ppm group appeared normal immediately post-exposure. With the exception of 1 animal with hair loss, rats from the 2312 ppm group had completely recovered within 11 days post-exposure. Signs of toxicity observed immediately post-exposure or during the 14-day observation period for the 4731 ppm group were death, decreased activity, tremors, convulsions, low carriage, splayed limbs, increased salivation, red/brown material around the nose and mouth, increased reactivity to handling, emaciation, closed eye, hunched posture, ungroomed appearance, abnormal gait, and body surface staining. For surviving animals in the 4731 ppm group, signs of toxicity generally resolved by day 9 post-exposure. Group mean body weights were moderately affected by exposure to the test item. Gross pathology revealed no organ specific test article-related macroscopic observations in these animals. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

Acute dermal toxicity

A key acute dermal toxicity study performed according to OECD TG 402 and in compliance with GLP with diethoxy(methyl)silane (CAS 2031-62-1) is available (WIL, 1996). In this limit test five Albino rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. The acute dermal LD50 value was calculated to be greater than 2000 mg/kg bw. No signs of clinical toxicity were reported and no mortalities occurred during the observation period. No remarkable changes or differences in body weights were recorded. No treatment- related gross necropsy findings were observed. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

Justification for classification or non-classification

The available data on acute toxicity of the registered substance do not meet the criteria for classification according to Regulation 1272/2008, and are therefore conclusive but not sufficient for classification.