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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Magnusson, B. and Kligman, A.M. The Identification of Contact Allergens by Animal Assay. The Guinea Pig Maximization Test. J. Invest. Dermatol. 4, 268 - 276 (1969).
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
[(2E)-3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-butenyl]triphenylphosphonium chloride
EC Number:
613-004-8
Cas Number:
62285-89-6
Molecular formula:
C28 H32 O2 P . Cl
IUPAC Name:
[(2E)-3-(5,5-dimethyl-1,3-dioxan-2-yl)-2-butenyl]triphenylphosphonium chloride
Details on test material:
- Name of test material (as cited in study report): C5-NPG-ACETAL
- Substance Number: 92/128
- Physical state: white powder
- Analytical purity: 99 %
- Lot/batch No.: 92/33 - 1 (Technikum B 15 S)
- Stability under test conditions: The stability of the test substance in aqua bidest. for at least 4 hours was confirmed by analysis.
- Storage condition of test material: refrigerator; exclusion of moisture

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, Extertal 1, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 291 - 333 g
- Housing: 5 animals per cage
- Diet (e.g. ad libitum): Kliba Labordiaet 341 (Kaninchen-Meerschweinchen-Haltungsdiaet), Klingentalmuehle AG, Kaiseraugst, Switzerland, ad libitum
- Water (e.g. ad libitum): Water ad libitum (tap water; about 2 g of ascorbic acid per 10 l water was added to the drinking water twice a week)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction: test substance 1% in 0.9% aqueous NaCl solution resp. in Freund's adjuvant / 0.9% aqueous NaCl solution 1 : 1) resp. 0.9% aqueous NaCl solution.
Percutaneous induction: test substance 25% in aqua bidest.
1st challenge: test substance 10% in aqua bidest.
2nd challenge test substance 10% in aqua bidest.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction: test substance 1% in 0.9% aqueous NaCl solution resp. in Freund's adjuvant / 0.9% aqueous NaCl solution 1 : 1) resp. 0.9% aqueous NaCl solution.
Percutaneous induction: test substance 25% in aqua bidest.
1st challenge: test substance 10% in aqua bidest.
2nd challenge test substance 10% in aqua bidest.
No. of animals per dose:
Pretest: 4
Main test: control group: 5; test group: 10
Details on study design:
RANGE FINDING TESTS:
For detecting a possible influence on irritating effects of previous intradermal treatment with Freund's adjuvant, animais pretreated with Freund's adjuvant / 0.9% aqueous NaCl-solution (1 : 1) each, in the same manner as intradermal induction about 3 weeks prior to the application of the test substance were used.

In the preliminary test after two 24-hour percutaneous occlusive applications within 96 hours the minimum irritant concentration was found to be a 25% test substance preparation in aqua bidest. and the maximum nonirritant concentration a 10% test substance preparation in aqua bidest. (48 hours after the beginning of application).

Applicability: it was possible to inject a 1% test substance preparation in 0.9% aqueous NaCl solution resp. in Freund's adjuvant / 0.9% aqueous NaC1-solution (1 : 1) with a syringe.

Readings: about 24 and 48 h after the beginning of application

PREPARATION OF THE TEST SUBSTANCE FORMULATIONS
- immediately before test substance application with Ultraturrax or with a magnetic stirrer (only adjuvant preparation)
- Formulations of the test substance were prepared gravimetrically; all concentrations were determined in weight/weight.

MAIN STUDY
A. INDUCTION EXPOSURE
- Form of application: intradermal and percutaneous occlusive
- Skin preparation: Clipping of the test animais: about 3 hours before each test substance application at the appropriate application sites
- Amount applied: 2 x 2 cm filter paper strips were applied to the skin of the flanks under an occlusive dressing (the bandage consists of rubberized linenpatches 4 x 4 cm and Fixomull(R) Stretch (adhesive fleece). The test filter paper strip was soaked in the test substance formulation; thus, the animais were exposed to about 0.15 g of the test substance formulation.
- No. of exposures: 6 intradermal injections in groups of two per animal
- Exposure period: The test substance was applied 2 times for 24 hours within a period of 96 hours in order to detect non-specific phenomena that are not caused by a sensitization reaction but could possibly be attributed to a shift in the irritation threshold.
- Test groups:
• Intradermal induction:
A) front row: 2 injections each of 0.1 ml Freund's adjuvant* without test substance emulsified with 0.9% aqueous NaCl-solution in a ratio of 1 : 1
B) middle row: 2 injections each of 0.1 ml of the test substance formulation
C) back row: 2 injections each of 0.1 ml Freund's adjuvant* / 0.9% aqueous NaCl-solution (1 : 1) with test substance
- Control group:
The animals were given the same injections (A, B, C) but without test substance, only with the formulating agent.
- Site: shoulder
- Frequency of applications: once
- Concentrations: 1 %
- Readings: about 24 after the beginning of application
• Percutaneous induction:
- Percutaneous induction was carried out one week after intradermal induction
- Amount applied: 2. x 4 cm filter paper strips were soaked in the test substance formulation (about 0.3 g) and applied to the skin of the shoulder under an occlusive dressing (the bandage consists of rubberized linenpatches 4 x 6 cm and Fixomull(R) Stretch (adhesive fleece).
The control animals were not treated since the distilled water used as formulating agent was not expected to influence the result of the study.
- Duration: 48 hours
- Site of application: shoulder, same area as in the case of the previous intradermal application
- Concentrations: 25 %
- Readings: 48 h after the beginning of application
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: First challenge 21 days after intradermal induction. A second challenge was carried out one week after the first one.
- Amount applied: 2 x 2 cm filter paper strips were soaked in the test substance formulation (about 0.15 g of the test substance) and applied to the skin of the flank under an occlusive dressing (the bandage consists of rubberized linenpatches 4 x 4 cm and Fixomull® Stretch (adhesive fleece).
- Exposure period: 24 hours
- Test groups: 1st challenge: treatment of the test group with the test substance formulation
2nd challenge: treatment of the test group with the test substance formulation
- Control group:
1st challenge: treatment of control group 1 with the test substance formulation (control group 2 remained untreated)
2nd challenge: treatment of control groups 1 and 2 with the test substance formulation
- Site: intact flank
- Concentrations: 10 %
- Evaluation (hr after challenge): 24 and 48 h after the removal of the patch


OTHER:
Positive control substance(s):
yes
Remarks:
a separate study will be performed twice a year

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
erythema score 2 in 3/10 animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: erythema score 2 in 3/10 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
erythema score 2 in 3/10 animals; edema scor in 1 / 10 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: erythema score 2 in 3/10 animals; edema scor in 1 / 10 animals.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
erythema score 3 in 2 /10 animals and score 2 in 2 / 10 animals.
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10 %. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: erythema score 3 in 2 /10 animals and score 2 in 2 / 10 animals..
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
erythema score 2 in 3 / 10 animals
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10 %. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: erythema score 2 in 3 / 10 animals.
Reading:
other: 1st and 2 nd reading as well as rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: other: 1st and 2 nd reading as well as rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
other: 1st and 2 nd reading as well as rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
other: Reading: other: 1st and 2 nd reading as well as rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1 %
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
erythema and edema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 1 %. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: erythema and edema.

Any other information on results incl. tables

GPMT

Intradermal induction:

- After intradermal induction well-defined erythema and slight edema were observed at the injection sites of the control group animals and test group animals at which only Freund's adjuvant/0.9% aqueous NaCl solution (1 : 1) was applied.

- Injection of the test substance preparation in 0.9% aqueous NaCl solution as well as in Freund's adjuvant/0.9% aqueous NaCl solution (1 : 1) caused necrotic skin changes and slight edema at almost all injection sites of the test group animals. A few injection sites exhibited well-defined erythema and slight edema.

- The control group animals injected with 0.9% aqueous NaCl solution did not show any skin reaction.

- The percutaneous induction was only carried out in the test group animals, because with aqua bidest. a vehicle was used, that was not expected to influence the result of the study.

- Necrotic skin changes (caused by the intradermal induction) and slight edema were observed.

- After the first challenge (24 hours after removal of the patch) 3 out of 10 animals of the test group showed well defined

erythema. Control group 1 did not show any skin reactions.

- The second challenge caused skin reactions in 4 out of 10 test group animals. Moderate to severe erytherna were observed in 2 animals and well-defined erythema in 2 animals (24 hours after removal of the patch).

- The animals of control groups 1 and 2 did not show any skin reactions.

- The evaluation of the results is based on the criteria of Annex VI/II D of the Council Directive of July 29, 1983 for the 5th Amendment of the Directive 67/548 EEC (= 83/467 EEC)).

- The number of animals sensitized is primarily taken into account in the evaluation. The control animals are used to rule out a substance-induced primary skin irritation.

- The findings obtained 24 hours after the removal of the patch are taken into account for the determination of the sensitization rate.

- The evaluation "sensitizing" has to be made if at least 30 percent of the experiment animals exhibit skin reactions in this adjuvant test.

- The positive control with 1-chlor-2,4-dinitrobenzol showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.

- Based on the results of the study under the test conditions chosen and taking the above cited evaluation criteria into account C5-NPG-Acetal has a sensitizing effect an the skin of the guinea pig in the Maximization Test.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Classification: sensitizing