Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diphenylsulfon (DPS)
- Substance type: organic
- Physical state: solid, white powder
- Analytical purity: > 99%
- Purity test date: 15/05/2001
- Lot/batch No.: 1712SA
- Expiration date of the lot/batch: 15/05/2002
- Stability under test conditions: not indicated
- Storage condition of test material: at room temperature in the dark
- Other: bulk density: 0.7-0.8
stability in vehicle (corn oil): not indicated

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River deutschland, kisslegg, Germany
- Age at study initiation: approximately 4 weeks old
- Weight at study initiation: individual body weights < 500 grams
- Housing: group housing of 5 animals per labelled metal cage (57 cm * 41 cm * 23 cm height) with wiremesh floors.
- Diet (e.g. ad libitum): Free access to standard guinea pig diet, including ascorbic acid (1000 mg/kg); (Charles River Breeding and Maintenance Diet for guinea pigs, Altromin, Lage, Germany). Certificates of analysis were examined and retained in the NOTOX archives. Hay (B.M.I., Helmond, The Netherlands) was provided twice a week.
- Water (e.g. ad libitum): Free access to tap water. Certificates of analysis were examined and retained in the NOTOX archives.
- Acclimation period: 4 days before the start of the treatment under laboratory conditions, instead of at least 5 days before the start of the study. However, this slight deviation from the protocol was considered not to have affected the study integrity.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +- 3°c
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs artificial fluorescent light


IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
50%
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
50%
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
Preliminary irritation study:
The selection of concentrations was based on the following criteria:
* the concentrations are well-tolerated by the animals
* for the induction exposures: the highest possible concentration that produced mild to moderate irritation (grades 2-3).
* for challenge exposure: the maximum non-irritant concentration.
A series of test substance concentrations was tested. Practical feasibility of administration determined the highest starting-concentration. The starting- and subsequent concentrations were taken from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1% and, if needed, further lower concentrations using the same steps.
The test system, procedures and techniques were identical to those used during the main study, unless otherwise specified. The animals selected (Himalayan strain, albino guinea pig (SPF-quality); Source: Biotechnology & Animal Breeding Division (RCC Ltd.), Füllinsdorf, Switzerland) were between 4 and 9 weeks old. No body weights were determined.
Initially, Initially the preliminary irritation study was performed for a Maximization study. Therefore, the test substance was also intradermally injected in the preliminary irritation study.
Intradermal injections:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could pass an injection needle. Each of two animals received two different concentrations in duplicate (0.1 ml/site) in the clipped scapular region. The injection sites were assessed for irritation 24 and 48 hours after treatment.
Epidermal application:
A series of 4 test substance concentrations was used, the highest concentration being the maximum concentration that could technically be applied. Two different concentrations were applied (0.5 ml each) per animal to the clipped flank using Metalline patches* (2*3 cm) mounted on Medical tape, which will be held in place with Micropore tape* and subsequently Coban elastic bandage*.
After 24 hours, the dressings were removed and the skin cleaned of residual test substance using water. The resulting dermal reactions were assessed for irritation 24 and 48 hours after exposure.
(* Suppliers: Lohmann GmbH, Neuwied, Germany (Metalline) and 3M, St. Paul, Minnesota, U.S.A. (Medical tape, Micropore and Coban).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 20
- Exposure period: days 1, 8 and 15
- Test groups: The left side of the scapular region was clipped and subsequently epidermally treated with 0.5 ml of a 50% test substance concentration, using Metalline patches (2*3 cm) mounted on Medical tape, which was held in place with Micropore tape and subsequently Coban elastic bandage.
After 6 hours, the dressings were removed and the skin cleaned of residual test substance. No induction readings were performed on day 15. The test substance concentration used for the induction phase was the highest possible test substance concentration. In the preliminary irritation study, this test substance concentration of 50% did not induce any skin reactions after the induction phase, this protocol deviation was considered not to have affected the study integrity.
- Control group: The control animals (10) were treated as described for the experimental animals, except that, instead of the test substance, vehicle alone was administered.
- Site: The left side of the scapular region
- Frequency of applications: on days 1, 8 and 15
- Duration: 6 hours
- Concentrations: 0.5 ml of a 50% test substance concentration,


B. CHALLENGE EXPOSURE
- No. of exposures: 20
- Day(s) of challenge: day 28
- Exposure period: 6 hours
- Test groups: The left flank of all animals was clipped and subsequently treated epidermally with a 50% (w/w) test substance concentration and the vehicle (0.1 ml of each), using Patch Test Plasters (Curatest®, Lohmann, Almere, The Netherlands). The patches were held in place with Micropore tape and subsequently Coban elastic bandage. After 6 hours, the dressings were removed and the skin cleaned of residual test substance and vehicle. The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the dressings.
The left flank was treated instead of the right flank. However, since no skin reactions were to be expected after induction and since no skin reactions were observed after challenge, this protocol deviation was considered not to have affected the study integrity.
- Control group: same treatment as experimental animals
- Site: The left flank
- Concentrations: 50% (w/w) test substance concentration and the vehicle (0.1 ml of each)
- Evaluation (hr after challenge): 24 and 48 hours after removal of the dressings


OTHER:
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
50% test substance
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% test substance. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no.

Any other information on results incl. tables

Induction phase: Skin effects were not recorded after the last (3rd) induction exposure.

Challenge phase: No skin reactions were evident after the challenge exposure in the experimental and control animals.

Toxicity/Mortality: no mortality occured and no symptomes of systemic toxicity were observed in the animals of the main study.

Body Weights: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
There was no evidence that diphenylsulfon (DPS) had caused skin hypersensitivity in the guinea pig, since no responces were observed in the experimental animals in the challenge phase. This result indicates a sensitation rate of 0%.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), diphenylsulfon (DPS) does not hve to be classified and has no obligatory labelling requirement for sensitation by skin contact.