Diethoxy(dimethyl)silane

Endpoint summary

Description of key information

Oral (similar to OECD 401), rat: LD50 = 9775 mg/kg bw

Inhalation (OCED TG 403), rat, 6 h exposure: LC50 > 42100 mg/m³ (limit test) (RA from CAS 1185 -55 -3)

Inhalation (OCED TG 403), rat, 4 h exposure: LC50 > 4700 mg/m³ (limit test) (RA from CAS 1112 -39 -6)

Inhalation (OCED TG 403), rat, 4 h exposure: LC50 > 13500 mg/m³ (limit test) (RA from CAS 2031 -67-6)

Dermal (similar to OECD 402), rabbit: LD50 = 13840 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No test material purity is stated in the study report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Wistar-derived

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3 - 4 weeks
- Weight at study initiation: 90 - 120 g
- Fasting period before study: none
- Diet: ad libitum (not further specified)
- Water: ad libitum (not further specified)

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.0, 8.0 and 16.0 mL/kg bw

Doses:

4.0, 8.0 and 16.0 mLkg bw

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD50

Effect level:

11.3 mL/kg bw

Based on:

test mat.

95% CL:

8.22 - 15.6

Remarks on result:

other: equivalent to: LD50 = 9775 mg/kg bw

Mortality:

No mortality occurred at dose levels of 4.0 and 8.0 mL/kg bw, respectively. 5/5 animals died during the study period when administered the test material at a dose level of 16.0 mL/kg bw.

Clinical signs:

other: Clinical signs such as hyperactivity, unsteady gait and sluggishness were observed in animals of all dose groups within 2 - 15 min after test material administration. In addition, labored breathing was recorded in animals of the highest dose group within

Gross pathology:

Gross pathology of dead animals revealed red/pink mottled livers, red adrenals, distended stomachs (gas-filled), tan/pink mottled glandular portions, pink kidneys, distended intestines (containing liquids, gas and blood, red/yellow sections). No abnormalities were found in surviving animals.

Table 1: Summary of mortality data

Dose [mL/kg bw]	Mortality
	N
Males
4.0	0/5
8.0	0/5
16.0	5/5

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 toxicity study conducted with rats, an LD50 of 9775 mg/kg bw was established after animals were administered a single dose of 4.0, 8.0 and 16.0 mL/kg bw. No mortality occurred at dose levels of 4.0 and 8.0 mL/kg bw, respectively. All animals (5/5) died after administration of 16.0 mL/kg bw. Therefore, the test substance does not need to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

9 775 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:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 700 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: CAS 1112-39-6

In a weight of evidence apporach three source substances are evaluated:

Dimethoxy(dimethyl)silane (CAS 1112 -39 -6): LC50 male/female rats > 4700 mg/m³ air (4h exposure)

Trimethoxy(methyl)silane (CAS 1185 -55 -3): LC 50 male/female rats > 7605 ppm (corresponding to 4210 mg/m³ (6h exposure)

Triethoxy(methyl)silane (CAS 2031 -67 -6): LC50 male/female rats > 13500 mg/m³ (4h exposure)

Interpretation of results:

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

Conclusions:

One read across acute inhalation study (CAS 1185-55-3) determined an LC50 value of > 7605 ppm (4210 mg/m³) for rats in a reliable study conducted according to current guideline, and in compliance with GLP (Dow Corning Corporation, 2006). No mortalities were reported. Clinical signs included urine staining, discoloured urine, fecal staining, head and muzzle soiling, with all females returning to normal by post exposure day 4. Four of the 5 males were reported normal by post exposure day 5, and all males were normal by post exposure day 10. Body weights and body weight gains were within normal limits over the duration of the study for all females. Two of the five males demonstrated weight loss during the first week post-exposure, with a return to normal weight gain during the second week. Necropsy findings included urinary bladder calculi and kidney foci in both sexes, an enlarged kidney in one male, and abcessed prostrate glands in two males. Urinary tract and prostate disease was attributed to urolithiasis of uncertain primary aetiology; a direct role for the test article in the formation of urinary calculi could neither be confirmed nor denied as a result of this study.

Another read across acute inhalation toxicity study which was conducted in compliance with GLP and according to OECD TG 403 reports an LC50 of >13500 mg/m³ for triethoxy(methyl)silane vapour (CAS 2031-67-6) in rats after 4 hours. One animal from a total of ten died. The study reported that it was technically not possible to determine the particle size, presumably because the substance was emitted mainly as vapour. It was not stated whether the tested concentration was the highest achievable concentration, but taking into account that the measured concentration (13.5 mg/L) greatly exceeds the saturated vapour concentration (Hoechst, AG 1991).
A third read across acute inhalation toxicity study was conducted in compliance with GLP and according to OECD TG 403. However the study report did not describe whether clinical examination and physical measurements were conducted. Exposure of rats to dimethoxydimethylsilane (CAS 1112-39-6) vapour at a concentration of 4.7 mg/L (4700 mg/m³) for four hours resulted in no mortality. Therefore LC50 was determined to be >4700 mg/m³ (DCC, 1989).

In a weight of evidence approach all three source substance did not show toxic effects leading to a classification. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute inhalation toxicity potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch score 1 and 2) from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No test material purity is stated in the study report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report, only 2 dose levels tested with 4 animals/dose group

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3 - 5 months
- Diet: ad libitum (not further specified)
- Water: ad libitum (not further specified)

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The trunk of the animals was exposed to the test material.
- Type of wrap if used: polyethylene sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: Excess of the test material is removed after the exposure period to prevent ingestion.
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

8.0 and 16 mL/kg bw

No. of animals per sex per dose:

4 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD50

Effect level:

16 mL/kg bw

Based on:

test mat.

95% CL:

4.48 - 57.2

Remarks on result:

other: equivalent to: LD50 = 13840 mg/kg bw

Mortality:

No mortality occurred at a dose level of 8.0 mL/kg bw (0/4), whereas 2/4 animals died during the study period when administered the test material at a dose level of 16.0 mL/kg bw.

Clinical signs:

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

Gross pathology:

Gross pathology of dead animals revealed red/pink or orange mottled livers, purple spleens and red kidneys. No abnormalities were found in surviving animals.

Other findings:

Neither erythema nor edema were recorded in 5/8 animals during the study period. 3/8 animals showed erythema and edema formation (grade 1) as well as ecchymosis and scabs after the 14-day study period.

Interpretation of results:

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

Conclusions:

In summary, the acute dermal LD50 value for male rabbits was considered to be 16 mL/kg bw (corresponding to 13840 mg/kg bw). Therefore, the test substance does not need to be classified for acute dermal toxicity according to Regulation (EC) No 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

13 840 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.

Additional information

Acute toxicity: oral

An acute oral toxicity study is available for the registered substance diethoxy(dimethyl)silane (CAS 78-62-6) which was conducted similar to OECD TG 401 (Chemical Hygiene Fellowship, 1979a). However, only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report. In this non-GLP study groups of five male Wistar-derived rats were administered the test material at concentrations of 4, 8 and 16 mL/kg bw (corresponding to 3460, 6920 and 13840 mg/kg bw) via oral gavage. The animals were observed for mortality, clinical signs of toxicity and body weight change after administration. No mortality occurred at dose levels of 4.0 and 8.0 mL/kg bw, respectively, whereas 5/5 animals died during the study period when administered the test material at a dose level of 16.0 mL/kg bw. Clinical signs such as hyperactivity, unsteady gait and sluggishness were observed in animals of all dose groups within 2 - 15 min after test material administration. In addition, labored breathing was recorded in animals of the highest dose group within 12 min after test material administration. Clinical signs had recovered within 2 h (4.0 mL/kg bw) and 4 h (8.0 mL/kg/bw), respectively. No detailed information on body weight changes is reported. Gross pathology of dead animals revealed red/pink mottled livers, red colored adrenals, distended stomachs (gas-filled), tan/pink mottled glandular portions, pink colored kidneys, distended intestines (containing liquids, gas and blood, red/yellow sections). No abnormalities were found in surviving animals. In summary, the acute oral LD50 value for male rats was calculated to be 11.3 mL/kg bw (corresponding to 9775 mg/kg bw).

 

Acute toxicity: inhalation

A non-reliable acute inhalation toxicity study is available for the registered substance diethoxy(dimethyl)silane (CAS 78-62-6) which was neither conducted to an appropriate OECD test guideline nor in compliance with GLP (Chemical Hygiene Fellowship, 1979b). However, only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report. In this acute inhalation study groups of six male Wistar-derived rats were exposed to a saturated vapor of the test material via whole body inhalation for 29, 57, 113 and 225 min. Mortality occurred 29 min (1/6), 57 min (3/6), 113 min (6/6) and 225 min (6/6) after exposure to a saturated vapor of the test material. Clinical signs such as lacrimation, ataxia, dyspnea, prostration and audible respiration were recorded in all exposure groups. No detailed information on body weight changes is reported. Gross pathology of dead animals revealed dark red colored lungs and gas-filled stomachs and intestines. No abnormalities were found in surviving animals. In summary, no effect level could be determined based on the limited reliability of the study.

Only non-reliable data on acute inhalation toxicity is available for diethoxy(dimethyl)silane (CAS 78 -62 -6). Therefore, the risk assessment was performed based on the available data from the source substances trimethoxy(methyl)silane (CAS 1185 -55 -3), triethoxy(methyl)silane (2031 -67 -6) and dimethoxy(dimethyl)silane (CAS 1112 -39 -6). 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 analogue substances has been applied to support the human health hazard assessment of diethoxy(methyl)silane (CAS 78 -62 -6). Further details are provided in the analogue justification attached to the respective target entry.

An acute inhalation study which was conducted in compliance with GLP and according to OECD TG 403. However the study report did not describe whether clinical examination and  physical measurements were conducted. Exposure of rats to dimethoxydimethylsilane (CAS 1112-39-6) vapour at a concentration of 4.7 mg/L (4700 mg/m³) for four hours resulted in no mortality. Therefore LC50 was determined to be >4700 mg/m³ (DCC, 1989).

An acute inhalation toxicity study which was conducted in compliance with GLP and according to OECD TG 403 with triethoxy(methyl)silane (CAS 2031 -67 -6) is available (Hoechst, AG 1991). A LC50 of >13500 mg/m³ for triethoxy(methyl)silane vapour in rats after 4 hours was determined. One animal from a total of ten died. The study reported that it was technically not possible to determine the particle size, presumably because the substance was emitted mainly as vapour. It was not stated whether the tested concentration was the highest achievable concentration, but taking into account that the measured concentration (13.5 mg/L) greatly exceeds the saturated vapour concentration.

A further study for acute inhalation performed according to OECD TG 403 in compliance with GLP is available with the read-across substance trimethoxy(methyl)silane (CAS 1185 -55 -3) is available (DCC, 2006). A LC50 value of > 7605 ppm (42.1 mg/L) for rats was determined. No mortalities were reported. Clinical signs included urine staining, discoloured urine, fecal staining, head and muzzle soiling, with all females returning to normal by post exposure day 4. Four of the 5 males were reported normal by post exposure day 5, and all males were normal by post exposure day 10. Body weights and body weight gains were within normal limits over the duration of the study for all females. Two of the five males demonstrated weight loss during the first week post-exposure, with a return to normal weight gain during the second week. Necropsy findings included urinary bladder calculi and kidney foci in both sexes, an enlarged kidney in one male, and abcessed prostrate glands in two males. Urinary tract and prostate disease was attributed to urolithiasis of uncertain primary aetiology; a direct role for the test article in the formation of urinary calculi could neither be confirmed nor denied as a result of this study.

Taking into consideration the above results generated from the structurally analogue substances the target substance diethoxy(dimethyl)silane (CAS 78 -62 -6) is not expected to be acute toxic via inhalation route.

  

Acute toxicity: dermal

An acute dermal toxicity study is available for the registered substance Diethoxy(dimethyl)silane (CAS 78-62-6) which was conducted similar to OECD TG 402 (Chemical Hygiene Fellowship, 1979c). However, only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report. In this non-GLP study groups of four male New Zealand White rabbits were exposed the test material at concentrations of 8 and 16 mL/kg bw (corresponding to 6920 and 13840 mg/kg bw) for 24 h via open dressing and observed for 14 days post-application. No mortality occurred at a dose level of 8.0 mL/kg bw, whereas 2/4 animals died during the study period when exposed to the test material at a dose level of 16.0 mL/kg bw. No clinical signs of toxicity were recorded during the study period. No detailed information on body weight changes is reported. Gross pathology of dead animals revealed red/pink or orange mottled livers, purple colored spleens and red colored kidneys. No such abnormalities were found in surviving animals. Neither erythema nor edema were recorded in 5/8 animals during the study period. 3/8 animals showed erythema and edema formation (grade 1) as well as ecchymosis and scabs after the 14-day study period. In summary, the acute dermal LD50 value for male rabbits was considered to be 16 mL/kg bw (corresponding to 13840 mg/kg bw).

Justification for classification or non-classification

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