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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (OECD 406): RA from CAS 31024-26-3, negative (Buehler); RA from CAS 3069-25-8, negative (GPMT)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 Dec 2012 - 13 Feb 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(2003)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Erlangen, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
The Buehler type of sensitization test was selected since the test substance is a functional silane and the Local Lymph Node Assay as the preferred alternative has shown to provide false positive results for silicone substances.
Species:
guinea pig
Strain:
other: Hartley (Crl:HA-Guinea Pigs (full barrier))
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 4 weeks old
- Weight at study initiation: 301-377 g
- Housing: in groups in Terluran-cages on Altromin saw fibre bedding (lot no. 011012)
- Diet: autoclaved hay and Altromin 3122 maintenance diet for guinea pigs (lot no. 1311/0807), rich in crude fibre, ad libitum
- Water: tap water (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% (neat test material)
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
No. of animals per dose:
- 2 for the preliminary test
- 20 in the test group of main study
- 10 in the negative control goup of the main study
Details on study design:
RANGE FINDING TESTS:
2 animals were treated topically with concentrations of 50% and 100% of the test item (suspended with vaseline) for 6 hours. Vaseline was chosen as vehicle due to its non-irritating characteristics. Based on the results of this preliminary test the following concentrations were chosen for the main test:
- 100% for the dermal inductions
- 100% for the challenge application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: a gauze patch loaded with 0.5 ml of the neat test substance
- Control group: a dry gauze patch, as no vehicle was used in the main study
- Site: left flank
- Frequency of applications: once a week
- Duration: Days 1-15
- Concentrations: 100% (undiluted)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: a gauze patch loaded with 0.5 ml of the neat test substance (right flank) and a dry gauze patch, as no vehicle was used in the main study (left flank)
- Control group: a gauze patch loaded with 0.5 ml of the neat test substance (right flank) and a dry gauze patch, as no vehicle was used in the main study (left flank)
- Site: right and left flanks
- Concentrations: 100% (undiluted)
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
The recent reliability check was performed in October/November 2012: mercaptobenzothiazole (purity 98%), 50% in vaseline (induction) and 25% in vaseline (challenge)
Positive control results:
In the most recent reliability check performed in October/November 2012 with mercaptobenzothiazole (purity 98%), 50% in vaseline (induction) and 25% in vaseline (challenge), the sensitization rate was 20%, confirming the reliability of the test system.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
checked on a regular basis at the test facility

Preliminary Test

2 animals were treated topically with concentrations of 50% and 100% of the test item (suspended with vaseline) for 6 hours. Based on the results of this preliminary test, a concentration of 100% was selected for the inductions as well as for the challenge. This concentration did not cause any signs of irritation after a topical treatment over a period of 6 hours.

Main Test

Dermal Induction I, II and III (6-hour exposure, occlusive):

- Immediately after removing the patch: no signs of irritation were observed in any of the animals

- 24 hours after removing the patch: no signs of irritation were observed in any of the animals

Challenge Exposure (6-hour exposure, occlusive):

- The results of the test animals at the challenge phase were compared to the results of the control animals. Neither erythema nor oedema was observed in any animal at any time of observation. There was no evidence of sensitisation and the percentage of sensitised animals was 0%.

- All animals of both groups survived throughout the test period. No signs of toxicity were recorded. The body weight development was within the biological range for all animals compared to historical data.

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 investigated for skin sensitising potential in a Buehler Test conducted in accordance with OECD TG 406 and in compliance with GLP. There were no signs of skin reactions after induction and challenge with the neat test material in any of the animals. Therefore, the test item is concluded to be not sensitising under the conditions of this test.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 - 30 Mar 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study conducted according to the appropriate OECD test guideline.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
no information on periodical reliability checks is reported
GLP compliance:
no
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:
other: Albino (Bor: DHPW)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 393 g (mean test group), 395 g (mean control group)
- Housing: Animals were housed in groups of 1 - 5 in Makrolon cages (type IV)
- Diet: G4 diet for guinea pigs (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 - 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
5 and 100%
Day(s)/duration:
0-14
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
100%
Day(s)/duration:
22
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (test group), 10 (control group)
Details on study design:
RANGE FINDING TESTS:
No detailed information on a range finding test is reported. The neat test material (100%) did not induce any skin reactions in the range finding test. Thus, animals were treated with 10% SDS (in vaseline) one day prior to epicutaneous application with the test material (induction phase).

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: a 1:1 mixture (v/v) FCA/water
Injection 2: 5% test substance in water (v/v)
Injection 3: 5% test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: 100% test substance

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: corn oil
Injection 3: corn oil at 50% (v/v) in a 1:1 mixture (v/v) FCA/water
Epicutaneous: corn oil
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: 22 (challenge)
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: left flank (test substance and vehicle)
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
no
Positive control results:
No information on periodical reliability checks reported.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
neither erythema nor edema observed
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: 5 and 100%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
neither erythema nor edema observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
neither erythema nor edema observed
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: 5 and 100%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
neither erythema nor edema observed
Group:
positive control
Remarks on result:
not measured/tested
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
In a GPMT according to OECD guideline 406, the test item was not sensitising. Induction (intradermal: 5%; topical: 100%) and challenge (100%) with the test item revealed no skin reactions in any of the 20 animals. Furthermore no skin reactions were observed in the negative controls (induction with corn oil, topical challenge with 100% test item).
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; Challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: CAS 31024-56-3, Buehler, BSL, 2013
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: 100%; Challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: CAS 31024-56-3, Buehler, BSL, 2013
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; Challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: CAS 31024-56-3, Buehler, BSL, 2013
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: 100%; Challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: CAS 31024-56-3, Buehler, BSL, 2013
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
checked on a regular basis at the test facility / CAS 31024-56-3, Buehler, BSL, 2013
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; Challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
neither erythema nor edema observed
Remarks on result:
other: CAS 3069-25-8, GPMT, Huls AG, 1990
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction: 5 and 100%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
neither erythema nor edema observed
Remarks on result:
other: CAS 3069-25-8, GPMT, Huls AG, 1990
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
neither erythema nor edema observed
Remarks on result:
other:
Remarks:
CAS 3069-25-8, Huls AG, 1990
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction: 5 and 100%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
neither erythema nor edema observed
Remarks on result:
other: CAS 3069-25-8, GPMT, Huls AG, 1990
Group:
positive control
Remarks on result:
not measured/tested
Remarks:
CAS 3069-25-8, GPMT, Huls AG, 1990
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No. 1272/2008.
Conclusions:
In the first key study, the source substance (CAS 31024-56-3) was investigated for skin sensitising potential in a Buehler Test conducted in accordance with OECD TG 406 and in compliance with GLP. There were no signs of skin reactions after induction and challenge with the neat test material in any of the animals. Therefore, the source substance is concluded to be not sensitising under the conditions of this test.

In the second key study, the source substance (CAS 3069-25-8) was investigated for skin sensitising potential in a GPMT conducted in accordance with OECD TG 406, but not in compliance with GLP. Induction (intradermal: 5%; topical: 100%) and challenge (100%) with the test item revealed no skin reactions in any of the 20 animals. Furthermore, no skin reactions were observed in the negative controls (induction with corn oil, topical challenge with 100% test item). Therefore, the source substance is concluded to be not sensitising under the conditions of this test.

As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in skin sensitising potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No data on skin sensitization is available with N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine (CAS 120939-52-8). Therefore, read across from the structurally similar source substances N-methyl-3-(trimethoxysilyl)-1-propanamine (CAS 3069-25-8) and N-[3-(trimethoxysilyl)propyl]-1-butanamine (CAS 31024-56-3) was applied. In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances has been applied to support the human health hazard assessment of N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine (CAS 120939-52-8).


 


In the first key study (BSL BIOSERVICE, 2013), the source substance N-[3-(trimethoxysilyl)propyl]butylamine (CAS 31024-56-3) was investigated for its skin sensitising potential in a Buehler Test according to the OECD test guideline 406, and in compliance with GLP. During the induction phase gauze patches with 0.5 ml of the neat test item were topically applied to the clipped flanks of 20 female Hartley guinea pigs once a week for three consecutive weeks, and were held in contact under occlusive conditions for 6 h. 10 female animals of the control group were subsequently treated in the same way with a dry gauze patch. For challenge exposure all animals of the control and test groups received a gauze patch loaded with 0.5 ml of the neat test material on the clipped right flank and a dry gauze patch on the clipped left flank. The patches were held in contact with the skin under occlusive conditions for 6 h. Approximately 21 hours after removing the patch, the challenge area was cleaned and cleared of hair by the use of a depilatory cream. Approximately 24 and 48 hours after removing the patch the skin reaction was observed and recorded. Additionally all animals were observed for signs of toxicity at least once daily during the test period. Neither erythema nor oedema was observed in any animal at any time of observation. There was no evidence of sensitisation and the percentage of sensitised animals was 0%. All animals of both groups survived throughout the test period. No signs of toxicity were recorded. The body weight development was within the biological range for all animals compared to historical data. The sensitivity of the strain was proven in a reliability check performed in October/November 2012. The test item was therefore concluded to be not sensitising to the skin under the conditions of this test.


 


In the second key study (GPMT, Hüls AG, 1990), source substance N-methyl-3-(trimethoxysilyl)propylamine (CAS 3069-25-8) was tested in a study according to OECD TG 406 using the Guinea pig maximization test. The GPMT test was performed on 20 female Albino (Bor: DHPW) guinea pigs. At the beginning of the induction exposure 20 test animals and 10 control animals were either intradermally treated with 5% of the test substance or vehicle (corn oil), followed by SDS treatment for induction of local irritation and topical induction (100% or vehicle) under occlusive conditions one week later. On Day 22 all animals were challenged with the test substance at a concentration of 100%. Skin reactions of all animals were evaluated 24 and 48 hours after challenge exposure (after removal of the patch). No skin reactions were observed for any animal neither in the control nor in the test group. No information on periodic reliability checks were reported. In conclusion, under the conditions of the test, the test substance revealed no skin sensitising properties.


 


Based on the available data for the source substances, the target substance N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine (CAS 120939-52-8) is also considered to be not skin sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Reliable data from structural analogues on skin sensitization indicates that the registered substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and the available data are therefore conclusive but not sufficient for classification.