Bis(trimethoxysilylpropyl)amine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 January - 16 February 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

yes

Remarks:

(no positive control data is given in the study report)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The test was performed in 1990 when the OECD Guideline 406 adopted in 1992 was the current version. According to this guideline "the Guinea Pig Maximisation Test (GPMT) [...] and the non-adjuvant Buehler Test are given preference over other methods.

Test material

Test material information

Constituent 1

Reference substance name:

Bis(trimethoxysilylpropyl)amine

EC Number:

280-084-5

EC Name:

Bis(trimethoxysilylpropyl)amine

Cas Number:

82985-35-1

Molecular formula:

C12H31NO6Si2

IUPAC Name:

3,3,11,11-tetramethoxy-2,12-dioxa-7-aza-3,11-disilatridecane

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Inc. (Denver, Pennsylvania, USA)
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 300-337 g (males), 300-350 g (females)
- Housing: individually in suspended stainless steel cages
- Diet: Agway Purina Guinea Pig Diet, ad libitum
- Water: automatic watering system, ad libitum, Municipal water supply (Elizabethtown Water Company)
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: monitored and recorded twice daily (not further specified)
- Humidity: monitored and recorded daily (not further specified)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: from 08 January - 16 February 1990

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Concentration / amount:

- intradermal injection: 5% (v/v)
- topical application: undiluted (100%)

Challenge

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

No. of animals per dose:

- range-finding: 3 males and 3 females
- test group (main study): 10 males and 10 females
- control group (main study): 5 males and 5 females

Details on study design:

RANGE FINDING TESTS:
To confirm that the concentration proposed for intradermal injection (5.0%) did not produce extensive necrosis or ulceration or severe systemic toxicity, two animals (1 male and 1 female) were administered intradermal injections (2 sites per animal) of a 5.0% (v/v) concentration of the test material in propylene glycol. Injections of 0.1 ml per site were made intradermally using a 1.0 cc syringe and a 25 gauge 5/8" needle. Observations were made at 24 and 48 hours for necrosis and ulceration. The results indicated that a 5.0% concentration produced only local necrosis (ie., no extensive necrosis or ulceration occurred). Therefore, this concentration was used for the intradermal induction administration.
A topical range-finding study was performed in 6 animals (3 males and 3 females) to determine the highest concentration which produced mild irritation (to be used for induction) and the highest concentration which did not produce irritation (to be used for challenge). Each of 3 male and 3 female guinea pigs had the following concentrations of the test substance applied to the dorsal and lateral
trunk areas of clipped skin; 10, 25 and 50% (v/v, in paraffin oil), and undiluted test material. Each concentration was tested by applyng 2 x 2 cm filter paper soaked solution of the material, and an occlusive bandage applied for 24 hr. Sites were inspected for signs of local irritation at 24 anh 48 hr after removal of the occlusive dressing. Since none of the concentrations of the test material produced any local erythema, edema, or ulceration, it was decided appropriate to use undiluted test material for both the epicutaneous induction and challenge procedures.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 50% (v/v) FCA in deionised water
Injection 2: 5 % (v/v) test substance in propylene glycol
Injection 3: 5% (v/v) test substance in 50% (v/v) FCA in deinosed water
Epicutaneous: 100% test substance
- Control group:
Intradermal (3 pairs of injections):
Injection 1: 50% (v/v) FCA in deionised water
Injection 2: propylene glycol
Injection 3: 50% (v/v) FCA in deinosed water (no vehicle was included due to a technician oversight)
Epicutaneous: vehicle
- Site: shoulder region (intradermal and epicutaneous; injection 1 and 2 were given close together and nearest to head; injection 3 was given more caudally);
- Frequency of applications: induction: every 7 days
- Duration: days 0-7
- Concentrations: 5% (v/v) intradermal and 100% epicutaneous

As the undiluted test substance is non-irritant the skin was pretreated with 10% sodium lauryl sulfate (w/w) 24 h prior to epicutaneous induction.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: flank
- Concentrations: undiluted (100%)
- Evaluation (hr after challenge): 24 and 48 h

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (DNCB)

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% at induction, 100% at challenge

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

5 males and 3 females showed desquamation.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5% at induction, 100% at challenge

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

1 female showed slight, well-defined and confluent erythema; 1 male and 1 female showed desquamation.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5% at induction, 100% at challenge

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

1 male showed desquamation

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5% at induction, 100% at challenge

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

1 female showed very slight, barely perceptible and non-confluent erythema.

Results 5

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

no data given in the report but periodically tested appr. every 4 to 6 months

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The test item was tested for skin sensitisation according to a test protocol that is comparable to the OECD 406 (Guinea Pig Maximization Test), and in compliance with GLP. For the induction exposure the test material was applied intradermal (5%) and epicutaneous (100%) to Hartley guinea pigs. The challenge exposure (topical application) was carried out with the undiluted test material. No skin reactions were observed 24 and 48 h after treatment with the test material in animals induced with the test item. One control animal showed slight erythema. Based on the findings, the test item is considered to be not sensitising to the skin. Based on this data, classification for skin sensitisation according to 67/584/EEC and EC/1272/2008 is not warranted.