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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
15 June 1993 to 23 July 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A LLNA does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction product of ammonium molybdate and C12-C24-diethoxylated alkylamine (1:5-1:3)
EC Number:
412-780-3
EC Name:
Reaction product of ammonium molybdate and C12-C24-diethoxylated alkylamine (1:5-1:3)
Cas Number:
1380226-46-9
Molecular formula:
A complex mixture of species so no unique molecular formula can be given
IUPAC Name:
dimolybdenum(6+) diammonium 2-{2-[(octadec-9-en-1-yl)amino]ethoxy}ethan-1-ol heptaoxidandiide
Test material form:
liquid: viscous
Details on test material:
- Name of test material: Additiv 104-Konzentrat
- Description: Dark red liquid
- Purity: Product by process; treated as 100% pure
- Lot/batch No.: DS 147
- Expiration date of the lot/batch: March 9, 1994
- Storage condition of test material: Room tempetrature in the dark
- Stability under storage conditions and up to 60 degrees C: Stable

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: Approx. 9 weeks
- Weight at study initiation: 346 — 461 grams
- Housing: Group housing of 2 animals per labelled metal cage with wire-mesh floors and equipped with an automatic drinking system (IlL, Bergen, The Netherlands).
- Diet (e.g. ad libitum): Free access to standard guinea pig diet,. including ascorbic acid (1600 mg/kg); LC 23—B, pellet diameter 4mm (Hope farms, Woerden, The Netherlands). In addition, hay (Broekman Institute, Sonieren, The Netherlands) was provided once a week
- Water (e.g. ad libitum): Free access to tap water, diluted with decalcified water
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): R elative humidity of 55%.
- Air changes (per hr): air-conditioned with 15 air changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was 12 hours artificial fluorescent light and 12 hours dark per day

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
propylene glycol
Concentration / amount:
Concentration of test substance and vehicle used at induction:

Intradermal Induction-
a) Test substance 1% (w/w) in propylene glycol
b) Freunds' complete adjuvant (FCA) 50:50 with water for injection
c) Test substance 2% (w/w) in FCA/water 1:1

Topical Induction-
Test substance 15% (w/w) in propylene glycol

Concentration of test substance and vehicle used for each challenge:
1.challenge 2. Re-challenge

a) 10% (w/w) in propylene glycol a) 0.1% (w/w) in propylene glycol

b) 5% (w/w) in propylene glycol b) 0.05% (w/w) in propylene glycol

c) 2% (w/w) in propylene glycol c) 0.02% (w/w) in propylene glycol

d) Propyleneglycol
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Concentration of test substance and vehicle used at induction:

Intradermal Induction-
a) Test substance 1% (w/w) in propylene glycol
b) Freunds' complete adjuvant (FCA) 50:50 with water for injection
c) Test substance 2% (w/w) in FCA/water 1:1

Topical Induction-
Test substance 15% (w/w) in propylene glycol

Concentration of test substance and vehicle used for each challenge:
1.challenge 2. Re-challenge

a) 10% (w/w) in propylene glycol a) 0.1% (w/w) in propylene glycol

b) 5% (w/w) in propylene glycol b) 0.05% (w/w) in propylene glycol

c) 2% (w/w) in propylene glycol c) 0.02% (w/w) in propylene glycol

d) Propyleneglycol
No. of animals per dose:
Number of animals in test group: 20 females
Number of animals in negative control group: 10 females
Details on study design:
INDUCTION - EXPERIMENTAL ANIMALS
Intradermal injections:
Day 1: The experimental animals were intradermally injected with three pairs of injections (0.1 ml/site) in the clipped scapular region. Concentrations of test substance and control used for the intradermal induction were as follows;
A) Test substance at a 1% (w/w) concentration in propylene glycol.
B) Freunds' complete adjuvant (FCA) 50:50 with water for injection.
C) Test substance, at twice the concentration used in (A), emulsified in a 50:50 mixture with FCA.

Epidermal applications:
Day 7: The area between the injection sites (6 x 8 cm) was clipped.
Day 8: The clipped area between the injection sites was treated with 0.5 ml of a 15% (w/w) test substance concentration in propylene glycol using a
Scotchpak-non-woven patch (2 x 4 cm) mounted on Micropore tape and secured with Coban elastic bandage. After 48 hours, the dressings and
residual test substance were removed. The skin reaction was assessed immediately after bandage removal.

INDUCTION - CONTROL ANIMALS
Day 1: The control animals were intradermally injected similar to described above with the omission of the test substance.
Day 8: The control animals were treated epidermally for 48 hours with propylene glycol only, using the similar patch as described above.
The treated area was assessed for erythema and oedema immediately after bandage removal.

CHALLENGE
Day 22: All animals were treated epidermally with a series of three test substance concentrations and propylene glycol (10%, 5% and 2%, w/w, 0.05 mlof each concentration and the vehicle) on the clipped and shaved left flank, using Square chambers attached to Micropore tape and secured with Coban elastic bandage. The dressings and residual test substance were removed after approximately 24 hours. The treated sites were assessed for redness and swelling 24 and 48 hours after removal of the dressings After the first reading, the test sites were shaved with an electric razor.

RE-CHALLENGE
Day 28: A second challenge was conducted one week after the first challenge, due to the inconclusive results obtained in the first challenge.
The method was similar to the first challenge for all animals except that the contralateral shaved flank of the animals was treated. The following three test substance concentrations and propylene glycol were applied: 0.1%, 0.05% and 0.02% (w/w) in propylene glycol.

At the end of the study period all animals were killed by intraperitoneal injection of Euthesate (A.U.V., Boxmeer, The Netherlands) 2 ml/animal.
Positive control substance(s):
yes
Remarks:
Formaldehyde (June 1993)

Results and discussion

Positive control results:
This positive control experiment was carried out to check the the test system as used by NOTOX, in accordance with the test in this report.
The positive control substance was Formaldehyde (batch 136K16536803)
Concentrations selected for this study were:
Intradermal induction: 1% (w/w) in physiological saline.
Epidermal induction: 1% (w/w) in distilled water.
Challenge 1:
a = 0.5% (w/w) in dist. water.
b = 0.2% (w/w) in dist. water.
c = 0.1% (w/w) in dist. water.
d = distilled water.
Challenge 2 (Re-Challenge)
a = 0.2% (w/w) in dist. water.
b = 0.1% (w/w) in dist. water.
c = 0.05% (w/w) in dist. water.
d = distilled water

Skin reactions were observed in the experimental and control animals in response to all three concentrations. However, it was clearly noted that a higher number of experimental animals showed a skin reaction than of the control animals and a higher degree of skin reaction in a few experimental animals in response to the three concentrations tested. A similar difference was noted in the first challenge skin sites and at histopathology examination. Therefore, it can be concluded that a clear sensitisation effect had occurred.From these results, it can be concluded that the Himalayan strain of guinea pig is an appropriate animal model for the performance of studies designed to evaluate the sensitising potential of a substance.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2 %
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2 %. No with. + reactions: 18.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2 %
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2 %. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5 %. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
2 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2 %. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5 %. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2 %
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2 %. No with. + reactions: 10.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 10 %

Signs of irritation during induction:

18 animals showed slight erythema

Evidence of sensitisation of each challenge concentration:
2nd challenge: up to 8 animals showed a positive reaction

Other observations:
No symptoms of systemic toxicity were observed.

Weight increase of test and control animals were similar.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Taking into account the intensity of the responses and comparing these with the skin reactions seen in the control animals in both challenges, it cannot be concluded that the skin reaction observed should be attributed to sensitisation reactions. These results lead to a sensitisation rate of 0 % which indicates that the test substancehas weak sensitizing properties in this test applying the rating of allergenicity described by Kligman AM. (1966).
Executive summary:

In a GLP compliant, guideline skin sensitisation test in the guinea pig the test substance was considered to have weak sensitizing properties. According to the EEC criteria for classification and labelling requirements of dangerous substances and preparations (EEC Directive 91/325/EEC, Amendment to Annex VI of the EEC Council Directive 67/548/EEC), the test substance need not be labelled as a skin sensitiser.