Bis(trimethoxysilylpropyl)amine

Endpoint summary

Description of key information

Skin sensitisation (similar to OECD 406 / GPMT): 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:

08 January - 16 February 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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.

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

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Concentration / amount:

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

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)

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.

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.

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In the available key study (Bio/Dynamics, 1990) the test item was tested for skin sensitising properties according to a test protocol that is similar to the OECD TG 406, and in compliance with GLP. 10 male and 10 female Hartley guinea pigs of the test group were used for this study. During the induction phase the animals were intradermally injected with 5% test item (diluted in propylene glycol) and, after treatment with sodium lauryl sulphate, topically treated with 100% test material. After a latency of 14 days (to allow a potential reaction with the immune system) the animals were challenged with 100% test material on the flank. The grade of skin reactions was compared to those of the 5 male and 5 female control animals, which were treated with 70% ethanol during the topical induction phase and, during the challenge phase, with the test item, respectively. The sensitisation rate after application of the test item was 0%. Under the test conditions described, the test item showed no sensitising effects. In the control group one animal showed slight erythema 24 and 48 h after challenge exposure. In both, the test and control group, few animals showed desquamation 24 h after the challenge exposure, which was cleared 48 h after challenge. No other signs of clinical toxicity were reported. Based on the results, the test item was considered not sensitising under the conditions of the test.

A second skin sensitisation study was available, but was disregarded due to a high number of reactions in the control animals (Hill Top Biolabs, 1988). The test item was tested for skin sensitisation according to a test protocol that is comparable to the OECD TG 406 (Guinea Pig Maximization Test), and in compliance with GLP. For the induction exposure the test material was applied intradermal (0.25%) and epicutaneous (5%) to Hartley guinea pigs. The first challenge exposure was carried out with 0.25% test material in mineral oil, resulting in 30% positive responders. As in the control animals skin reactions (grade 1 erythema) were observed, positive responders were defined as responders with grade 2 reactions. To overcome the high number of reactions in the control animals, a re-challenge with acetone as solvent was performed, thereby increasing the test substance concentration to 2.5%. Positive responders were defined as animals with grade 1 reactions, as in the control animals only grade 0.5 or no reaction was observed. 5% and 10% positive responders (24 h and 48 h after re-challenge, respectively) have been observed. However, the skin reactions, which exceeded the control values, cannot conclusively be correlated with sensitising effects but might also be the result of irritation. Hence, a clear result on the sensitising properties of the test item could not be obtained under the conditions of the test.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on this data, classification for skin sensitisation according to 67/584/EEC and EC/1272/2008 is not warranted.