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Administrative data

Description of key information

In the key study for skin sensitisation performed according to OECD Test Guideline 406 and in compliance with GLP, (3-chloropropyl)triethoxysilane (CAS 5089 -70 -3; EC 225 -805 -6) was not sensitising to the skin of guinea pigs (Dow Corning Corporation, 1995e).

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:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.
Species:
guinea pig
Strain:
other: Crl: (HA)BR
Sex:
male
Details on test animals and environmental conditions:
The animals were housed in individual hanging stainless steel wire mesh cages in an animal room with controlled temperature (70-73 °F = 21.1 - 22.8 °C ), humidity (45-56%) and light (12hours light and 12 hours dark). Diet (Certified Guinea Pig Chow® #5026, Purina Mills, Inc., St. Louis, Missouri) and water were free available. The animals were acclimated for 16 days prior to the first induction dose. Male animals free from physical abnormalities and of the appropriate body weight range were made available for selection and were placed into groups using a computer-generated random number sequence program. Each guinea pig was identified by a Monel® metal ear tag bearing the individual animal number. The body weight range of the day of intradermal injections was 408-533 grams. The guinea pigs were young adult animals, approximately 1 ½ months of age at the start of the study.
Route:
intradermal
Vehicle:
cotton seed oil
Concentration / amount:
Intradermal injection: 5% (Site 1: 0.1 mL of a 50% solution of FCA in 0.9% sodium chloride injection; Site 2: 0.1 mL of 5% test substance in cottonseed oil; Site 3: 0.1 mL of 5 % test substance in cottonseed oil in FCA/0.9% sodium chloride for injection (50/50 mixture)
Day(s)/duration:
Day 1 for intradermal induction
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
Topical application: 75% test article in cottonseed oil
Day(s)/duration:
Days 8/ 48h of application for dressing
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
cotton seed oil
Concentration / amount:
Topical application: Epicutaneous patch 75% left flank; vehicle alone right flank
Day(s)/duration:
Day 22/ 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 males in test article-treated group
10 males in negative control group
10 males in positive control group
Details on study design:
RANGE FINDING TESTS: A primary irritation screening study was conducted to determine the concentration of the test article to be employed in the induction and challenge phases. The backs of the guinea pigs were clipped within one day prior to dosing. Test sites in the shaven area of each animal were treated with 0.1 mL of the test article (in cottonseed oil) by intradermal injections using a different glass 1/2 cc syringe for each concentration and a different sterile 26 gauge needle for each test site at 0.5, 1, 2, 4 or 5% w/v or by topical patch application at 25, 50, 75, and 100% w/v of the test article (prepared with cottonseed oil) by saturating a 2x2 cm patch of Whatman No3 filter paper with test article. The topical patches were held in place with tape and overwrapped. The bandaging materials were removed 24 hours later. Approximately 24 hours prior to the first observation, the test sites were shaved with an electric clipper and the skin cleansed of any residual test article (patched animals only). The intradermal injection sites were observed for irritation at approximately 24 and 48 hours after dosing. The topical patch test sites were observed for irritation at approximately 24 and 48 hours after patch removal.
Based on the results of the screening studies, concentrations of 5% (intradermal injection) and 75% (topical patch) were selected for the induction phase, and a 75% test article concentration was selected for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE: intradermal and topical
- No. of exposures: Two: intradermal injections and topical applications of the test article to stimulate the immune system
- Exposure period: Single injection (intradermal) ; 48 hours (topical)
- Test groups:
Intradermal: Injection 1: 0.1 mL of a 50% solution of FCA in 0.9% sodium chloride injection; Injection 2 : 0.1 mL of 5% test substance in cottonseed oil; Injection 3: 0.1 mL of 5 % test substance in cottonseed oil in FCA/0.9% sodium chloride for injection (50/50 mixture)
Topical: One day following the sodium lauryl sulfate application (10% in distilled water to enhance sensitisation), animals were administered topical exposure via a closed patch application to the shoulder area. A 75% concentration of the test article in cottonseed oil was used to saturate a 2x4 cm patch filter paper. The patch was placed on the injection area.
Control group:
Intradermal: Negative control group: Injection 1: 0.1 mL of a 50% solution of FCA in 0.9% sodium chloride injection; Injection 2 : 0.1 mL of cottonseed oil neat; Injection 3: 0.1 mL of 50 % cottonseed oil in FCA/0.9% sodium chloride for injection (50/50 mixture)
Intradermal: Positive control group: Injection 1: 0.1 mL of a 50% solution of FCA in 0.9% sodium chloride injection; Injection 2 : 0.1 mL of 0.1% 2,4-DNCB in 80% ethanol; Injection 3: 0.1 mL of 0.1% 2.4-DNCB in 80% ethanol in FCA/0.9% sodium chloride for injection (50/50 mixture)
Topical: positive control group: 0.5% of 2.4-DCNB in petrolatum applied in a thick even layer on a 2x4 cm patch of filter paper.
Topical: negative control group: patches saturated with cottonseed oil neat.
- Site: Shoulder region

During the intradermal induction stage, the test group of 20 animals were dosed intradermally with duplicate injections of 1:1 FCA:saline, a 5% w/v mixture of the test substance in cottonseed oil and a 5% w/v mixture of the test substance in 1:1 FCA:saline. The negative control group of ten animals were injected with 1:1 FCA:saline, undiluted cottonseed oil and a 50% w/v mixture of cottonseed oil in 1:1 FCA:saline. The positive control group of ten animals was injected with 1:1 FCA:saline, a 0.1% w/v mixture of 2,4-DNCB in 80% ethanol and a 0.1% w/v mixture of 2,4-DNCB in 1:1 FCA:saline. One week after the intradermal injections, the area was clipped free of hair and treated with 10% sodium lauryl sulfate (SLS) in distilled water in order to enhance sensitization. On the day following the SLS application, a patch saturated with 75% test article in cottonseed oil or control articles (negative group was topically induced with cottonseed oil neat; positive controls were topically induced with a 0.5% w/v concentration of 2,4-DNCB in petrolatum) was applied to the injection area of treated and control animals, respectively, and covered with an occlusive dressing for 48 hours.

B. CHALLENGE EXPOSURE: topical
- No. of exposures: One
- Day(s) of challenge: Day 22
- Exposure period: 24 hours
- Test groups: 75% concentration of the test article in cottonseed oild was used to saturate a 2x4 cm patch filter paper (left flank); vehicle on the right flank
- Control group: Positive : 0.25% w/v solution of 2.4-DNCB in petrolatum on left flank and a patch of petrolatum neat on the right flank; Negative: patch saturated with vehicle cottonseed oil on right flank and 75% test substance on the left flank

On the day prior to challenge dosing, the flanks of each guinea pig were clipped free of hair. Fourteen days after topical induction on study day 22, all test and negative control animals were challenged with 75% w/v mixture of test substance in cottonseed oil on the anterior left flank and the vehicle, cottonseed oil, on the anterior right flank. Positive control group animals received a topical challenge dose of a 0.25% w/v solution of 2,4-DNCB in petrolatum on the anterior left flank and the vehicle, petrolatum, on the anterior right flank. All challenge doses were applied on previously unexposed areas of skin. The patches were occluded with plastic wrap and over wrapped with tape for 24 hours. Twenty-four hours after dosing, the occlusive cover was removed and the sites washed with tepid water.
Application sites were evaluated at approximately 24 and 48 hours after patch removal. Sites were graded on a scale of 0 to 4 for both erythema/eschar formation and edema formation. During the test animals were observed twice daily for mortality. Individual body weights were recorded prior to intradermal injection and at a study termination.
Challenge controls:
See above
Positive control substance(s):
yes
Remarks:
2.4-DNCB
Positive control results:
Positive response observed in all positive control animals.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75% test article
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
vehicle (cottonseed oil)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75% test article
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle (cottonseed oil)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75% test article
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle (cottonseed oil)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75% test article
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle (cottonseed oil)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.25% 2,4-DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
vehicle (petrolatum)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.25% 2,4-DNCB
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.25% 2,4-DNCB. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
vehicle (petrolatum)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: vehicle (petrolatum). No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximisation study conducted according to OECD Test Guideline 406 and in compliance with GLP, (3-chloropropyl)triethoxysilane did not induce skin sensitisation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The key sensitisation study was selected as the most recent guideline study available from four reliable tests (DCC, 1995e), and was therefore assigned reliability 1. The key study, and two reliability 2 supporting studies (TNO-CIVO, 1980 and Laboratorium Für Pharmakologie und Toxikologie, 1976) were guinea pig maximisation tests. In addition, a reliability 1 study using the Buehler method is available (Hüls AG, 1993). All four studies gave clear negative results.

(3-Chloropropyl)triethoxysilane (CAS 5089-70-3; EC 225-805-6) has been tested in a Guinea-Pig Maximisation test conducted according to OECD Test Guideline 406 and in compliance with GLP. During the induction phase, male guinea pigs were injected intradermally with 5% (w/v) test material (in cottonseed oil), then after treatment with sodium lauryl sulfate, treated topically with 75% (w/v) test material via a closed patch application to the shoulder area. After a latency of 14 days, to allow a potential reaction of the immune system, the animals were challenged with 75% test substance on the flank. Negative and positive controls were used and the guinea pigs were observed for a sensitisation response following the challenge phase. No animals in the test group or in the negative control group had a sensitisation response. All positive control animals had a sensitisation response. The sensitisation rate for the test substance was 0 %, therefore it is not considered to be a skin sensitiser (Dow Corning Corporation, 1995e).

In a supporting skin sensitisation study using the Buehler method, conducted according to OECD Test Guideline 406 and in compliance with GLP, (3-chloropropyl)triethoxysilane was applied undiluted to 19 guinea pigs over an area of 0.35/0.4 cm3 and occluded. Negative control animals were used, but a positive control substance was not included. Challenge was conducted on study day 28 with undiluted test material (occlusive epicutaneous). At 24-, 48-, and 72-hours post-application, no skin irritation was observed in either test animals or control animals. There were no substance-related effects on body weight in either test or control animals. Based on the non-adjuvant sensitisation test in guinea pigs (3-chloropropyl)triethoxysilane was not sensitising (Hüls AG, 1993).

Two other studies (TNO-CIVO, 1980 and Laboratorium Für Pharmakologie und Toxikologie, 1976) were conducted prior to the adoption of the OECD Test Guideline and GLP. However, they meet generally accepted scientific principles and support the conclusions that the registered substance does not produce sensitisation reactions in the skin of guinea pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on reliable in vivo studies, (3 -chloropropyl)triethoxysilane does not require classification for skin sensitisation according to Regulation 1272/2008. There are no data to suggest that the substance should be classified as a respiratory sensitiser.