Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
A re-challenge is done after 16 not 7 days. Testing additional animals is strongly recommended when fewer than 20 test and 10 control guinea pigs have been used and it is not posible to conclude that the test substance is a sensitiser.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because the test method is not considered to be suitable for substances that contain silicon. Please refer to the attached document for further details.

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(triethoxysilyl)propiononitrile
EC Number:
213-050-5
EC Name:
3-(triethoxysilyl)propiononitrile
Cas Number:
919-31-3
Molecular formula:
C9H19NO3Si
IUPAC Name:
3-(triethoxysilyl)propanenitrile
Constituent 2
Reference substance name:
3-(triethoxysilyl)propionitrile
IUPAC Name:
3-(triethoxysilyl)propionitrile

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Remarks:
Albino CRL:(HA)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg / Germany
- Number of Animals for Main Study /Pretest:15 males / 3 males
- Age at Pretest Start / Beginning of Acclimatization Period: 5-6 weeks
- Body Weight at Pretest Start: Pretest groups: 680 -715 g
- Body Weight at Beginning of Acclimation Period: Test and control group: 604 - 748 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst /Switzerland).
- Diet: Pelleted standard Provimi Kliba 3418 guinea pig breeding / maintenance diet batch nos. 44/09 and 52/09, containing Vitamin C (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland), ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
- Water: Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.
- Identification: By unique cage number and corresponding individual ear tag.
- Randomization: Selected by hand at time of delivery. No computer generated randomization program.
- Acclimation period: Twelve days for the control and test group under laboratory conditions after health examination. No acclimation period for the animals of the pretest. Only animals without any visible signs of illness were used for the study. A certificate of health was provided by the animal supplier at the animal delivery and included in the raw data.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Air-conditioned with ranges for room temperature 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark
- Room temperature and humidity were monitored continuously and values outside of these ranges occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at Harlan Laboratories. Music was played during the daytime light period.

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
other: Diethylene glycol dimethyl ether (glyme)
Concentration / amount:
Intradermal induction : 0.1 mL of 50% test substance in vehicle and in FCA/physiological saline
Epidermal induction: 0.3 mL of 100% test substance in vehicle
Day(s)/duration:
Day 1 for intradermal induction, Day 8 for epidermal induction/48h of application for the closed patch
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Diethylene glycol dimethyl ether
Concentration / amount:
0.2 mL of the test item at 25% in vehicle (and vehicle alone)
Day(s)/duration:
Day 22/ 24h of application
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: Diethylene glycol dimethyl ether
Concentration / amount:
0.2 mL of the test item at 25% in vehicle (and vehicle alone)
Day(s)/duration:
Day 38/ 24h of application
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
15 (10 test and 5 control) male albino Dunkin Hartley guinea pigs
Details on study design:
The dose levels of 3-(triethoxysilyl)propiononitrile used in the main study were based on results from intradermal and epidermal pretests.
The intradermal induction of sensitization in the test group was performed in the nuchal region with a 50% dilution of the test item in diglyme and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 100% (undiluted) one week after the intradermal induction. The animals of the control group were intradermally induced with diglyme and FCA/physiological saline and epidermally induced with diglyme under occlusion. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 25% in diglyme and diglyme alone under occlusive dressing. Sixteen days after the first challenge a second challenge was performed in the same way as the previous challenge using the test group only and the test item at 25% in diglyme applied on a naive skin site.
Challenge controls:
The animals of the control group were intradermally induced with diglyme and FCA/physiological saline and epidermally induced with diglyme under occlusion.
Positive control substance(s):
yes
Remarks:
ALPHA-HEXYLCINNAMALDEHYDE at 1% (w/w) in PEG 300

Results and discussion

Positive control results:
The sensitivity and reliability of the experimental technique employed was assessed by use of ALPHA-HEXYLCINNAMALDEHYDE which is recommended by the OECD 406 Guidelines and is known to have moderate skin sensitization properties in the guinea pig strain. The results from the most recent test run (Harlan Laboratories Study C50652, performed from 27-May-2009 to 20-Jul-2009) ) follow:
One out of 10 test animals showed skin reactions after the first challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 1% (w/w) in PEG 300. No skin effect was observed in the control group. Eighty to ninety percent of the test animals showed discrete/patchy erythema at the 24- or 48-hour reading
after the second challenge treatment with ALPHA-HEXYLCINNAMALDEHYDE at 3% (w/v) in PEG 300. No skin effect was observed in the control group.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
Grade 2
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0
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:
test chemical
Dose level:
25%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Grade 1 in 3 animals, Grade 2 in 2 animals
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0
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:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Grade 1 in all animals
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Grade 1
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
positive control
Dose level:
3%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
Grade 1
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
3%
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
Grade 1
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

Table 1: Skin Reactions after the First Challenge Procedure

 

After 24 hours

Positive/Total

% Positive of Total

After 48 hours

Positive/Total

% Positive of Total

Control Group

3-(TRIETHOXYSILYL) PROPIONONITRILE, 25% in diglyme

(left flank)

 

 

Diglyme only

 

1/5

20

 

 

 

0/5

0

 

0/5

0

 

 

 

0/5

0

 

Test Group

3-(TRIETHOXYSILYL)PROPIONONITRILE,

25% in diglyme

(left flank)

 

Diglyme only

 

5/10

50

 

 

0/10

0

 

 

4/10

40

 

 

0/10

0

 Table 2: Skin Reactions after the Second Challenge Procedure

 

After 24 hours

Positive/Total

% Positive of Total

After 48 hours

Positive/Total

% Positive of Total

Test Group

3-(TRIETHOXYSILYL)PROPIONONITRILE,

25% in diglyme

(left flank)

 

Diglyme only

 

1/10

10

 

 

0/10

0

 

0/10

0

 

 

0/10

0

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
In a guinea pig maximisation test study with adjuvant, conducted according to OECD Test Guideline 406 and in compliance with GLP (with minor deviations), 3-(triethoxysilyl)propiononitrile is not considered to be a skin sensitiser.