Tetraethyl orthosilicate

Endpoint summary

Description of key information

In the key skin irritation study conducted according to OECD Test Guideline 404 and in compliance with GLP (Degussa-Huls AG 1992, reliability score 1), tetraethyl orthosilicate (CAS No. 78-10-4, EC No. 201-083-8) was mildly irritating to the skin of rabbits, with erythema and oedema dissipating within 6-10 days and all symptoms dissipating within 14 days.

 

In the key eye irritation finding (Mellon Institute of Industrial Research 1940, reliability score 2), workers exposed to tetraethyl orthosilicate vapours during laboratory animal studies showed irritation of the eyes and nose at concentrations of 250 ppm vapour (approximately 2.1 mg/L) and above. In comparison, two supporting studies conducted according to OECD Test Guideline 405 studies and in compliance with GLP (Degussa-Huls AG 1992 and Hoechst AG 1991, both reliability score 1) determined that tetraethyl orthosilicate is not irritating to the rabbit eye.

 

For respiratory irritation, the data available for workers (Mellon Institute of Industrial Research 1940) also indicates that tetraethyl orthosilicate vapours are irritating to the nose of humans.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992/10/05-1992/10/20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

other: Small white Russian, Chbb: MH, SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Dr. Karl Thomae GmbH Co, Biberach

- Weight at study initiation: 2-3 kg

- Housing: Conventional, individual containment in stainless steel cages

- Diet: Ssniff K 4-comprehensive feed for rabbits, ad libitum

- Water: municipal water, ad libitum

- Acclimation period: minimum of 14 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 20 +/-3

- Humidity (%): 30-70

- Air changes (per hr): 15

- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Remarks:

other: intact skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of test substance

- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 hours

Observation period:

The treated area was scored for irritation at 30-60 minutes, 24, 48 and 72 hours following patch removal and on days 6, 8, 10 and 14 following patch removal.

Number of animals:

3M

Details on study design:

TEST SITE
- Area of exposure: 6 cm2 of shaved intact dorsal skin

- Type of wrap if used: covered with a layer of gauze, which was covered with a non-stick dressing and a semi-occlusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with warm water.  

- Time after start of exposure: 4 hours

SCORING SYSTEM: According to guideline

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild irritation

Remarks:

median

Irritant / corrosive response data:

Semi-occlusive application of tetraethyl orthosilicate caused localized medium erythema, and medium edema in all three animals after 24 hrs. These signs dissipated within 6 to 10 days.

Other effects:

Skin dryness and dandruff were evident as the erythema and edema alleviated, but these additional symptoms resolved within 14 days.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

 

Score at time point / Reversibility	Erythema	Edema
	Max. score: 3	Max. score: 4
60 min	2/2/2	4/3/3
24 h	2/3/2	3/3/3
48 h	2/3/2	2/3/2
72 h	2/3/1	1/3/1
6 days	1/2/0	1/2/0
8 days	1/0/0	1/0/0
10 days	0/0/0	0/0/0
14 days	0/0/0	0/0/0
Median 24h, 48h, 72h	2.22	2.33
Reversibility*)	c	c
Average time (unit) for reversion	6-10 days	6-10 days

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Remarks:

Not classified according to Regulation (EC) No. 1272/2008

Conclusions:

In the key study conducted according to OECD Test Guideline 404 and in compliance with GLP (reliability score 1), tetraethyl orthosilicate was found to produce medium erythema and medium edema in the rabbit, with these symptoms dissipating within 6 to10 days, and all symptoms dissipating within 14 days. Tetraethyl orthosilicate is a non-irritant under Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

other: laboratory worker exposure

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report presents the experience of workers engaged in animal laboratory studies using tetraethyl orthosilicate.

Principles of method if other than guideline:

Workers were exposed to vapours of tetraethyl orthosilicate during the handling and use of the material for laboratory studies in animals.

GLP compliance:

no

Species:

human

Vehicle:

unchanged (no vehicle)

Remarks:

worker exposure to vapours during laboratory studies in animals

Controls:

no

Amount / concentration applied:

85, 250, 700, 1200 and 3000 ppm, vapour
animal, and presumed worker, exposure concentrations

Duration of treatment / exposure:

"brief" exposure, details not specified

Observation period (in vivo):

none

Number of animals or in vitro replicates:

number workers exposed not specified

Details on study design:

Laboratory workers were exposed to tetraethyl orthosilicate vapours at the test concentrations used for guinea pig and rat vapour inhalation studies.

Irritation parameter:

other: 3000 ppm, vapour

Basis:

other: worker

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

other: extremely irritating to eyes and nose of workers

Irritation parameter:

other: 1200 ppm, vapour

Basis:

other: worker

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

other: stings eyes and nose of and produces tears in workers

Irritation parameter:

other: 700 ppm, vapour

Basis:

other: worker

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

other: mildly stings eyes and nose of workers, 700 ppm could be tolerated by workers for approximately 30 minutes

Irritation parameter:

other: 250 ppm, vapour

Basis:

other: workers

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

other: makes eyes and nose of workers tingle slightly

Irritation parameter:

other: 85 ppm, vapour

Basis:

other: worker

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

other: can be detected as odor by workers

Interpretation of results:

other: irritating to the human eye

Conclusions:

As the key eye data, workers exposed to tetraethyl orthosilicate vapours during pre-OECD guideline / pre-GLP laboratory animal studies showed irritation of the eyes and nose at concentrations of 250 ppm vapour (ca. 2.1 mg/L) and above. Concentrations of 700 ppm vapour (ca. 6.0 mg/L) could be tolerated by workers for approximately 30 minutes. This human finding is assigned reliability score 2. Compared to their studies in the guinea pig and rat (see 7.2.2.224), the authors concluded that human eyes and nose were more sensitive to tetraethyl orthosilicate vapours.

The eye irritant effects in laboratory workers support the Eye Irritation Cat 2 (H319, Causes serious eye irritation) classification in Annex VI of Regulation (EC) No. 1272/2008. This classification is assessed qualitatively as a "low hazard" for this endpoint following REACH Guidance Part E, Table E.3-1.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

SKIN

For skin irritation, the tetraethyl orthosilicate data consist of:

- Key OECD Test Guideline 404 (Degussa-Huls AG 1992, reliability score 1)

- Supporting in vitro study with the Skin2 TK-1350 and Corrositex systems (Dow Corning Corporation 1994, reliability score 2)

- Two additional supporting studies with reliability score 4. However, these studies both pre-date OECD guidelines and GLP.

 

In the key study conducted according to OECD Test Guideline 404 and in compliance with GLP (Degussa-Huls AG 1992, reliability score 1), 0.5 mL of tetraethyl orthosilicate (no vehicle) was applied to shaved intact skin of rabbits under semi-occlusive conditions for 4 hours and then rinsed off. Tetraethyl orthosilicate was found to produce medium erythema and medium oedema in all three animals, with these symptoms dissipating within 6 to 10 days. Skin dryness and dandruff were evident as the erythema and oedema alleviated, but these additional symptoms resolved within 14 days. The median individual 24/48/72-hour scores for erythema were 1.67, 2, and 3, and for oedema were 2, 2, and 3. Tetraethyl orthosilicate is a non-irritant for skin under Regulation (EC) No. 1272/2008.

 

A supporting study was conducted according to an acceptable alternative method (non-GLP), specifically evaluating tetraethyl orthosilicate using the in vitro Skin2 TK-1350 and Corrositex systems for corrosion (Dow Corning Corporation 1994, reliability score 2). The Skin2 TK-1350 system found that tetraethyl orthosilicate was not corrosive. However, the Corrositex system did not work with tetraethyl orthosilicate indicating this method could not be used to assess most silicone / alkoxysilanes as of the study date. The Skin2 TK-1350 result supports the key study findings.

 

EYE

For the eye, the data for tetraethyl orthosilicate include:

- Key finding of eye irritation for tetraethyl orthosilicate is based on a report for laboratory workers (Mellon Institute of Industrial Research 1940, reliability score 2)

- Two supporting rabbit studies (OECD Test Guideline 405, Degussa-Huls AG 1992, Hoechst AG 1991, both reliability score 1) indicating no irritation

- Three additional supporting studies with reliability score 4. However, these studies either pre-date OECD guidelines and GLP, or the guideline and GLP status are not indicated.

While the key human finding (eye irritation) and the reliable supporting animal data (not irritating to the rabbit eye) do not align, tetraethyl orthosilicate is currently classified in Annex VI of Regulation (EC) No. 1272/2008 as Eye Irritation Cat 2 (H319, Causes serious eye irritation). See Justification for classification / non-classification.

 

The key available evidence for eye irritation is from laboratory workers exposed to tetraethyl orthosilicate vapours (Mellon Institute of Industrial Research 1940, reliability score 2). Workers exposed to tetraethyl orthosilicate vapours during pre-OECD guideline / pre-GLP laboratory animal studies exhibited irritation of the eyes at concentrations of 250 ppm vapour (approximately 2.1 mg/L) and above. Concentrations of 700 ppm vapour (approximately 6.0 mg/L) could be tolerated by workers for approximately 30 minutes.

 

In the primary (most recent) animal study conducted according to OECD Test Guideline 405 and in compliance with GLP (Degussa-Huls AG 1992, reliability score 1), 1 mL undiluted tetraethyl orthosilicate was applied to rabbit eyes for 24 hours and then rinsed. All individual scores for corneal opacity, iris, conjunctivae, and chemosis were 0 at 24, 48 and 72 hours. This result does not support the key finding among human workers.

 

In a supporting rabbit study conducted according to OECD Test Guideline 405 and in compliance with GLP (Hoechst AG 1991, reliability score 1), 1 mL undiluted tetraethyl orthosilicate was applied to rabbit eyes for 24 hours and then rinsed. All individual scores for corneal opacity, iris, and chemosis were 0 at 24, 48 and 72 hours. The individual scores for conjunctivae were 1 at 24 hours, and 0 at 48 and 72 hours, with individual 24/48/72-hour means of 0, 0, and 0.33. Tetraethyl orthosilicate was not irritating to the rabbit eye. This result does not support the key finding among human workers.

 

RESPIRATORY TRACT

In terms of respiratory tract irritation, the data available for workers (Mellon Institute of Industrial Research 1940, reliability score 2) also indicates that tetraethyl orthosilicate vapours are irritating to the nose of humans at concentrations of 250 ppm vapour (approximately 2.1 mg/L) and above. As discussed in more detail under Justification for classification / non-classification, tetraethyl orthosilicate is currently classified in Annex VI of Regulation (EC) No. 1272/2008 as STOT SE Cat 3 (H335, May cause respiratory irritation).

Justification for classification or non-classification

For skin irritation, tetraethyl orthosilicate is a non-irritant based on the key reliable study and following Regulation (EC) No. 1272/2008.

 

For irritation of the eye, tetraethyl orthosilicate is currently classified in Annex VI of Regulation (EC) No. 1272/2008 as Eye Irritation Cat 2 (H319, Causes serious eye irritation). Evidence of irritation of the eyes of workers exposed to tetraethyl orthosilicate vapours supports this classification.

 

In terms of respiratory tract irritation, tetraethyl orthosilicate is currently classified in Annex VI of Regulation (EC) No. 1272/2008 as STOT SE Cat 3 (H335, May cause respiratory irritation). Irritation of the nose among workers exposed to tetraethyl orthosilicate vapours supports this classification.

 

For both eye and respiratory tract irritation, the Annex VI classifications are assessed qualitatively as a “low hazard” for these endpoints following REACH Guidance Part E, Table E.3-1.