Trimethoxypropylsilane

Endpoint summary

Description of key information

Buehler test according to OECD 406: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Pretest: 05 - 08 Aug 1996. Main test: 07 Oct - 06 Nov 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Type of study:

Buehler test

Justification for non-LLNA method:

An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Buehler test method, that was performed prior to the adoption of OECD 429.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, GERMANY
- Age at study initiation: young adults
- Weight at study initiation: <500 g
- Housing: Makrolon Type IV, max 5/cage
- Diet: Ssniff G 4-diet for Guinea Pigs, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

100%

Day(s)/duration:

3 single treatments (6 h exposure), Days 0, 7 and 14

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

25%

Day(s)/duration:

single treatment (6 h exposure), Day 28

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Pre-test: 6
Main test: 20 (test group); 10 (control)

Details on study design:

RANGE FINDING TESTS:
Applications (6 h occluded contact) of 5, 25, 50 and 100% TS with examination at 24 and 48 h following patch removal. 100% was identified as a suitable induction concentration (causing mild irritation), while 25% was identified as the lowest non-irritant challenge concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 dermal occlusive
- Exposure period: 6 h
- Test groups: neat test substance (0.3 mL applied to a 2x2 cm patch)
- Control group: verhicle corn oil (0.3 mL applied to a 2x2 cm patch)
- Site: left flank
- Frequency of applications: application on Days 0, 7, 14
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (at two sites: TS and vehicle)
- Day(s) of challenge: Day 28
- Exposure period: 6 h
- Test groups: test substance in corn oil and corn oil only
- Control group: test substance in corn oil and corn oil only
- Site: posterior right flank (test substance) and anteriour right flank (vehicle)
- Concentrations: 25%
- Evaluation (hr after challenge): 24 and 48 h following patch removal

Challenge controls:

The control group is actually a control.

Positive control substance(s):

yes

Remarks:

2-mercaptobenzothiazol (MCBT)

Positive control results:

Response rate of 30% (3/10 animals) indicates that the standard allergen is a sensitizer in the guinea pig under the conditions of this study. (See table 1.)

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25% test item

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25% test item

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25% test item

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25% test item

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

50% MCBT

No. with + reactions:

3

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Table 1: Incidence of dermal response to challenge dosing

GROUP	MATERIAL	INTERVAL (AFTER 6h CHALLENGE)	SKIN REACTIONS (NUMBER OF ANIMALS)	NUMBER OF ANIMALS	SENSITIZATION INCIDENCE INDEX**
Test	TS (25%)	24h	0	20	0/20=0%
		48h	0	20
	Vehicle	24h	0	20	0/20=0%
		48h	0	20
Positive control (2-mercaptobenzothiazol)	50% MCBT in vehicle	24h	3	10	3/10=30%*
		48h	0	10
	Vehicle (Vaseline)	24h	0	5	0/5=0%
		48h	0	5
Negative (vehicle) control	TS (25%)	24h	0	10	n/a
		48h	0	10
	Vehicle	24h	0	10	n/a
		48h	0	10

* The response of 30% in the positive controls confirms that the standard allergen tested is sensitizing in guinea pig under the conditions of this study.

Interpretation of results:

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

Conclusions:

In a guinea pig skin sensitisation study (Buehler test), conducted according to OECD 406 and to GLP (reliability score 1) trimethoxy(propyl)silane was not a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In the available key study (Hüls AG, 1997) the test item trimethoxy(propyl)silane (CAS 1067-25-0) was tested for skin sensitising properties according to OECD 406 (Buehler test) and in compliance with GLP. Corn oil was used as the vehicle / negative control. The test species was the Dunkin-Hartley Guinea pig (20 and 10 animals in the test and control groups, respectively). During the induction phase the test item was applied at 100% for 6 h on Days 0, 7 and 14. During the challenge phase (Day 28), the test item was applied at 25% in corn oil for 6 h. Evaluation of the dermal responses were made at 24 and 48 h following patch removal. The sensitisation rate after application of the test item was 0%. The positive control substance 2-mercaptobenzothiazol showed the expected sensitization response demonstrating the test system functioned correctly. Under the test conditions described, the test item showed no sensitising effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on sensitisation 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.