Trimethoxypropylsilane

Endpoint summary

Description of key information

Skin irritation (OECD 404): irritating
Eye irritation (OECD 405): not irritating

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:

5 - 19 May 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

minor deviations: coverage occlusive; limited information on test material (e.g. no data on purity or batch no.)

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Asta-Werke AG, Bielefeld, GERMANY
- Age at study initiation: 6 months
- Weight at study initiation: 2.3-2.8 kg
- Housing: 1/cage
- Diet: standard ad libitum
- Water: drinking water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 15
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1987-05-05 To: 1987-05-19

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml
- Concentration: neat (100%)

Duration of treatment / exposure:

4 h

Observation period:

Examination 1, 24, 48, 72 h following removal of patch. Further observation up to 14 days.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm²
- Type of wrap if used: gauze patch, synthetic foil cover, occlusive wrap

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Scaling to the end of the observation period

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Scaling to the end of the observation period

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Scaling to the end of the observation period

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

Clear defined erythema and slight edema in all three animals. Scaling to the end of the observation period (14 days).

Table 1: Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 4
1 h	1,0,0	1,0,1
24 h	2,2,2	2,2,2
48 h	2,1,2	2,2,2
72 h	2,2,1	2,2,2
Average 1h, 24h, 48h, 72h	1.42	1.67
Irritation index (1h, 24h, 48h, 72h)	3.1
Individual mean scores (24h, 48h, 72h)	2/1.67/1.67	2/2/2

Erythema or oedema were seen for up to 8 days, scaling continued to study termination at 14 days. (Limited information appear to be presented on observations post-72h.)

No systemic toxicity was reported.

Interpretation of results:

other: CLP/EU GHS criteria are met, Category 2 (irritant) classification required according to Regulations (EC) No. 1272/2008

Conclusions:

In a skin irritation study conducted largely in accordance with OECD 404, but without GLP status (reliability score 2), trimethoxy(propyl)silane was irritating to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 - 12 May 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 1981

Deviations:

yes

Remarks:

incomplete details on the identity and purity of the test substance.

GLP compliance:

no

Species:

rabbit

Strain:

other: Albino White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Asta-Werke AG, Bielefeld, GERMANY
- Age at study initiation: 6 months
- Weight at study initiation: 2.0-2.4 kg
- Housing: individually in stainless-steel cages (Model: ASTA)
- Diet: Sniff standard diet for rabbits, but no indication of whether it was ad libitum
- Water: Ad libitum
- Acclimation period: at least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 55 +/-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: n/a - neat

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

6 days
Reading time points: 1, 24, 48 and 72 h and then once daily until Day 6 (scores for Days 4-6 are not given in the report)

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

Irritation index of 10.4 (out of a total possible of 110) was judged, in the report, to fall within the range 0-10 indicating no irritation.

Other effects:

No systemic toxicity was detected.

Table 1: Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility*	Cornea		Iris	Conjunctivae
	Opacity - Max. score 4 (a)	Area - Max. score 4 (b)	Max. - score 2 (c)	Redness - Max score 3 (d)	Chemosis - Max. score 4 (e)	Discharge -Max. score 3 (f)
60 min	0/0/0	0/0/0	0/0/0	2/3/3	0/2/0	0/1/1
24 h	0/1/0	0/4/0	0/1/0	1/3/2	0/2/0	0/1/0
48 h	0/1/0	0/4/0	0/0/0	0/3/2	0/1/0	0/0/0
72 h	0/1/0	0/4/0	0/0/0	0/2/1	0/0/0	0/0/0
Average 24h, 48h, 72h	0.3	1.3	0.1	1.6	0.3	0.1
Mean scores (3 animals; 4 time points) out of maximum possible	5/80		0.4/10	5/20
Total score (irritation index)** (max 110)	10.4/110

*Each entry shows values for each of the 3 animals

**Maximum total score irritation index = ([axbx5] + [cx5] + [(d+e+f)x2])/18

Interpretation of results:

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

Conclusions:

A reliable eye irritation study, conducted according to OECD 405 but not GLP, reported an irritation index of 10.4 out of 110. The index was judged in the report to indicate that the test material was not irritating to the eyes of rabbits. This finding would concur with a reading according to CLP/EU GHS criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

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.

There are two reliability score 2 studies available for both skin and eye irritation. Therefore, the most recent of the studies were selected as the key studies. For eye irritation, the second study supported the findings of the key study. For skin irritation the supporting study gave a result of not irritating, and was therefore not in agreement with the key study. However, this study appeared (based on translation of the German report) to be limited in its reporting of observations after 72 hours.

 

Skin Irritation

In the available key study trimethoxy(propyl)silane (CAS 1067-25-0) was tested for skin irritation according to the OECD 404, but not to GLP (ASTA-WERKE, 1987). 0.5 mL of the test item was applied to the shaved, intact skin of three White Russian rabbits and was covered using an occlusive dressing for four hours. Examinations of the skin were made 1, 24, 48 and 72 h after patch removal. Further observations were made at 14 days. Mean erythema scores (24/48/72 h) were 1.67 in two animals and 2 in the third animal, mean oedema scores were 2 for each animal. Erythema and oedema were seen for up to 8 days and scaling continued to study termination at 14 days. No systemic toxicity was reported. Overall, trimethoxy(propyl)silane was concluded to be irritating to the skin of rabbits. 

 

An additional skin irritation study was conducted according to Federal Register (1973). 38, 187 (1500.41 - skin), the study pre-dates the OECD test guidelines and GLP (INBIFO, 1979). Six New Zealand White rabbits were exposed to the test item for 24 hours on intact and abraded skin. Erythema and oedema were graded at 24 and 72 h following treatment. The test item was found to be non-irritating to the skin of rabbits.

 

Eye Irritation

In the available key study trimethoxy(propyl)silane (CAS 1067-25-0) was tested for eye irritation according to the OECD 405, but not to GLP (ASTA-WERKE, 1987). 0.1 mL of the unchanged test item was instilled into the eyes of three Albino White Russian rabbits. Redness of the conjunctivae was the most prominent effect. It was seen in all three animals to a varying degree (score: 0.33 - 2.67, mean over 24, 48 and 72 h). All effects were reversible within six days of treatment. Overall, the scores in the report indicate that trimethoxy(propyl)silane does not warrant classification for eye irritancy. 

 

An additional eye irritation study was conducted according to Federal Register (1973). 38, 187, (1500.42 - eye), the study pre-dates the OECD test guidelines and GLP (INBIFO, 1979). The test item was instilled into the eyes of six New Zealand White rabbits, signs of irritation were graded at 24, 48 and 72 hours post application. The test item was found to be non-irritating to eyes of rabbits.

Justification for classification or non-classification

The available data on eye irritation of the registered substance do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification. The available data on skin irritation of the test substance meet the criteria for classification as Skin Irrit. 2 (H315) according to Regulation (EC) No. 1272/2008.