Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No . 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

EC Number:

913-404-5

Molecular formula:

Unspecified

IUPAC Name:

Reaction mass of iodine and 2-Pyrrolidinone, 1-ethenyl-, homopolymer

Details on test material:

- Purity: ≥ 92%- pH: ≥ 1 - ≤ 5 (aqueous preparation)

Specific details on test material used for the study:

- Name of test substance : PVP-lod 30/06- Test substance No.: 04/0282-1- Batch No.: Lot: G 2295BPZ0- Date of production: October 15, 2002- Physical state / appearance : Solid / brown- Degree of purity / content: 97.2 g/100 g- Homogeneity: The test substance was homogeneous by visual inspection.- Stability: The stability under storage conditions was confirmed by reanalysis- Storage conditions: Room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Remarks:

Crl:HA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS- Source: Charles River Kisslegg- Age at study initiation: About 6 weeks- Weight at study initiation: 343 g - 423 g- Housing: Stainless steel wire mesh cages with plastic-coated grating, minimum floor area: 2,000 cm2, 5 animals per cage.- Diet: Kliba Labordiät (Kaninchen/ Meerschweinchen-Haltungsdiät) Provimi Kliba SA, Kaiseraugst, Switzerland ad libitum- Water: Tap water ad libitum- Acclimation period: 14 days before the first test substance application .ENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 24- Humidity (%): 30 - 70- Air changes (per hr): fully air-conditioned rooms- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: 0.9% aqueous NaCI-solution or Freund's adjuvant / 0.9% aqueous NaCI-solution (1:1)

Concentration / amount:

5% test substance preparation in 0.9% aqueous NaCI-solution or 5% test substance preparation in Freund's adjuvant / 0.9% aqueous NaCI-solution (1:1)

Adequacy of induction:

other: Induction caused intense erythema and swelling at the injection sites of the test substance preparation in all test group animals.

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

1 mL of 25% test substance

Adequacy of induction:

other: After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test group animals.

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.5 mL of 10% test substance

Adequacy of challenge:

not specified

No. of animals per dose:

Number of animals per control group: 5Number of animals of the test group: 10

Details on study design:

RANGE FINDING TESTS: Intradermal Pre-test: 6 intradermal injections in groups of two per animal were applied to each animal .A) front row: 2 injections each of 0.1 mL Freund's adjuvant without test substance emulsified with 0.9% aqueous NaCI-solution in a ratio of 1:1B) middle row: 2 injections each of 0.1 mL of a test substance formulation in an appropriate vehicle at the selected concentrationC) back row: 2 injections each of 0.1 mL Freund's adjuvant / 0.9% aqueous NaCI-solution (1:1) with test substance at the selected concentration.- Site of application: neck region- No . of animals: 2 per test substance concentration- Reading: 24 h after the beginning of applicationEpicutaneous Pre-test: For detecting a possible influence on irritating effects of previous intradermal treatment with Freund's adjuvant, animals pre-treated with Freund's adjuvant / 0 .9% aqueous NaCI-solution (1:1) each, in the same manner as intradermal pre-test referring front row (A) and back row (C) without test substance about 2 weeks prior to the application of the test substance were used .- Amount applied: 2 x 2 cm gauze patches (6 layers surgical gauze) containing 0.5 mL of the test substance formulation were applied to the skin of the flanks under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 4 cm), patches of Idealbinde (5 x 5 cm) and Fixomull® Stretch (adhesive fleece).- Duration of exposure: 24 hours- Site of application: flank- Number of test animals: 3 per test substance concentration- Readings: 1 h, 24 h and 48 h after removal of the patchesMAIN STUDYINDUCTION EXPOSURE - IntradermalIntradermal injections in groups of two per animal were given.A) front row: 2 injections each of 0.1 mL Freund's adjuvant without test substance emulsified with 0.9% aqueous NaCI-solution in a ratio of 1:1B) middle row: 2 injections each of 0.1 mL of the undiluted vehicle or 0.1 mL of a test substance formulation in an appropriate vehicle at the selected concentrationC) back row: 2 injections each of 0.1 mL of a 50% formulation of the vehicle without test substance emulsified with Freund's adjuvant/ 0.9% aqueous NaCI-solution (1:1) or 0.1 mL Freund's adjuvant / 0.9% aqueous NaCI-solution (1:1) with test substance at the selected concentration.- Site of application: neck region- Reading: 24 h after the beginning of applicationINDUCTION EXPOSURE - EpicutaneousEpicutaneous induction was carried out one week after intradermal induction.- Amount applied: 2 x 4 cm gauze patches (6 layers surgical gauze) containing the test substance formulation were applied to the skin of the neck region under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 6 cm) and Fixomull® Stretch (adhesive fleece). 1 mL of the test substance formulation was applied to each animal. 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 of exposure: 48 hours- Site of application: neck region, same area as in the case of the previous intradermal application- Readings: directly after removal of the patchCHALLENGE EXPOSUREThe challenge was performed 14 days after the epicutaneous induction.- Amount applied: 2 x 2 cm gauze patches (6 layers surgical gauze Ph . Eur. from Lohmann GmbH & Co . KG) containing the test substance formulation were applied to the skin of the flank under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 4 cm from Russka), patches of Idealbinde (5 x 5 cm from Pfälzische Verbandstoff-Fabrik) and Fixomull® Stretch (adhesive fleece) from Beiersdorf AG. 0.5 mL of the test substance formulation was applied to each animal.- Duration of exposure: 24 hours- Site of application: intact flank- Readings: 24 and 48 h after the removal of the patch

Challenge controls:

A positive control (reliability check) with a known sensitizer is not included in this study. However, a separate study is performed twice a year in the laboratory. The positive controls with Alpha-Hexylcinnamaldehyde showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.

Positive control substance(s):

yes

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Slight yellow discoloration of the application areas. This did not impair evaluation of erythema formation. The expected body weight gain was generally observed in the course of the study.

Remarks on result:

no indication of skin sensitisation

Remarks:

Since no borderline results were observed, a 2nd challenge was not performed .

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met