Registration Dossier

Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 August - 1 October, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No information on the purity of the test material. It seems that the test was conducted using an adaptation of the method of Ritz and Buehler. Historical control data was provided after the study was carried out.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
The potential of Busan 11-M1, at a concentration of 75% (W/V) in distilled water, to produce delayed contact hypersensitivity in Guinea pigs was evaluated using an adaptation of the method of Ritz and Buehler.
GLP compliance:
yes (incl. certificate)
Type of study:
other: Adaptation of the method of Ritz and Buehler

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Busan 11-M1
- Substance type: No data
- Physical state: White powder
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No.: 8-11866
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Inc.
- Age at study initiation: young adult
- Weight at study initiation: 329 - 526 g
- Housing: Individually in wire mexh suspension cages
- Diet (e.g. ad libitum): Purina Guinea pig Chow (or comparable) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 25/08/1988 To: 01/10/1988

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Pilot 1: 0.5, 1.0, 2.5, 5.0, 10, 25, 50, 75 % (W/V) in distilled water
Induction: 75 % (W/V) in distilled water
Challenge: 75 % (W/V) in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Pilot 1: 0.5, 1.0, 2.5, 5.0, 10, 25, 50, 75 % (W/V) in distilled water
Induction: 75 % (W/V) in distilled water
Challenge: 75 % (W/V) in distilled water
No. of animals per dose:
Primary irritation: 4/sex/dose
Test (induction of sensitization and primary challenge): 10/sex/dose
Positive control: 5/sex/dose
Details on study design:
RANGE FINDING TESTS:
Sites are prepared by clipping the hair on the day before application of the test article. An appropriate volume of test article is applied into the selected patch system. The animal is placed into the restrainer and the patches applied to the clipped skin surface. The patches are occluded with a rubber dental dam pulled taut and fastened to the bottom m of the restrainer with clips. The restrainer is adjusted to minimise movement of the animal during exposure. 6 hours later the dental dam and patches are removed and the animal is removed from the restrainer and replaced in its cage. Excess material may be removed. On the day following exposure, the animals are depilated and scored.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 1 group male and female 75 % (W/V):
- Control group: No induction on control group
- Site: left sholder
- Frequency of applications: weekly
- Duration: 6 hours
- Concentrations: 75 % (W/V) in distilled water

B. CHALLENGE EXPOSURE
- No. of exposures: 1 on
- Day(s) of challenge: 2 weeks after induction
- Exposure period: 6 hours
- Test groups: 1 group male and female 75 % (W/V)
- Control group: 1 group male and female 75 % (W/V)
- Site:not previously exposed
- Concentrations: 75 % (W/V) in distilled water
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Ten animals (naive control) which have never been exposed to the test article are treated with the same concetnration as the test animals.
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-Dinitrobenzene

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75 % (W/V)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
incidence of +/- reactions comparable to controls
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 % (W/V). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: incidence of +/- reactions comparable to controls.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75 % (W/V)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
some +/- reactions observed
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75 % (W/V). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: some +/- reactions observed.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75 % (W/V)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
incidence of +/- reactions comparable to controls
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 % (W/V). No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: incidence of +/- reactions comparable to controls.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75 % (W/V)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
some +/- reactions observed
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75 % (W/V). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: some +/- reactions observed.

Any other information on results incl. tables

No further data

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Following primary challenge there were no grades of 1 produced in the test or control animals. The incidence of grade ± responses in the test group, was compared to that of the naive control group. The incidence and severity of these responses in the test group were essentially comparable to those produced by the naive control group and this indicated that sensitisation had not been induced. Therefore no classification is warranted for sensitisation.
Executive summary:

In a study conducted by Kreuzmann (1988), Guinea pigs were induced by applying patches of 75% (w/v) of the test substance, Busan 11-M1, to clipped exposure sites on the left shoulders of the animals. The 6 hour exposures were carried out weekly for 3 weeks. Two weeks later patches of the test substance were applied in the same manner for an exposure period of 6 hours to the test group and a naive control group at a concentration of 75% (w/v) of Busan 11-M1. At the test concentration used in this study, the test substance did not elicit allergenic responses and as such, is not considered to be a potential skin sensitiser. Based on these results, the test substance does not warrant classification for skin sensitisation in accordance with Regulation EC No. 1272/2008.