Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD Guideline 406, U.S. EPA OPPTS 870.2600 (2003), and EU Guideline 92/69, Annex V, B6 (1992)
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Purity: 99.6%
NB No. 1079166A

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Upon arrival, all animals were housed in individual suspended wire-mesh cages.

The basal diet and municipal water, delivered by an automatic watering system, were provided ad libitum.

The animal room was maintained with controlled temperature, humidity and light (12 hours light/12 hours dark). The room temperature and humidity controls were set to maintain daily averages of 66 ± 5°F (19 ± 3°C) and 50 ± 20% relative humidity.

Actual mean daily temperature ranged from 65.5°F to 67.4°F (18.6°C to 19.7°C) and mean daily relative humidity ranged from 26.2% to 92.4%
during the study.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test material was applied undiluted.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Test material was applied undiluted.
No. of animals per dose:
10/sex
5/sex (negative controls)
Details on study design:
INDUCTION PHASE:
The test article, undiluted ARCOSOLV® DPnP, was administered at 0.3 mL/site. Doses were applied under 25-mm Hill Top Chambers®, occluded with plastic wrap and overwrapped with nonirritating elastic tape. Induction doses were applied to the same site on the anterior left flank of all Test Group animals. Test Group animals received three induction doses spaced one week apart over a period of three weeks. All induction exposures were six hours, after which the bandages were removed and the sites wiped with disposable paper towels moistened with tepid tap water. Naive Control-I Group animals remained untreated during the Induction Phase.

CHALLENGE PHASE:
The Challenge Phase consisted of a single application of the maximal nonirritating concentration of test article to determine if delayed contact hypersensitivity had occurred. Two weeks after the final induction dose, an undiluted concentration of the test article, ARCOSOLV® DPnP, was administered to unexposed sites on the posterior left flank of the Test and Naive Control-I Group animals at 0.3 mL/site. Doses were applied under 25-mm Hill Top Chambers® that were occluded with plastic wrap and overwrapped with nonirritating elastic tape. All challenge exposures were six hours, after which the bandages were removed and the sites wiped with disposable paper towels moistened with tepid tap water.
Challenge controls:
Naive Control-I Group animals remained untreated during the Induction Phase.
Positive control substance(s):
no

Study design: in vivo (LLNA)

Concentration:
not applicable
No. of animals per dose:
not applicable
Details on study design:
not applicable
Statistics:
not applicable

Results and discussion

Positive control results:
None

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.3 mL
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.3 mL. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.3 mL
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.3 mL. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: None .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: not applicable
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: not applicable

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, ARCOSOLV® DPnP did not cause skin sensitization in albino guinea pigs.
Executive summary:

The sensitization potential of ARCOSOLV® DPnP was evaluated in this modified Buehler method dermal sensitization study. A Test Group of 10 male and 10 female Hartley albino guinea pigs was dosed topically with the test article one time per week for three weeks for a total of three induction exposures. The duration of each exposure was six hours. Two weeks after the last induction exposure, the animals were challenge-dosed for detection of sensitization by topical application of the test article to previously unexposed areas of skin. A Naive Control-I Group of 5 male and 5 female guinea pigs was dosed with the test article at challenge in the same manner as the Test Group and served as an irritation control. Reactions to challenge dosing were evaluated at approximately 24 and 48 hours after completion of exposure. Body weights and clinical observations were recorded at randomization (study day -1) and at study termination (study day 30).

Positive control data were not generated as part of this study. WIL historical positive control data from a study conducted within six months of this test were used to demonstrate the reliability of the experimental design.

There were no deaths, test article-related clinical findings or remarkable body weight changes during the study period. Following challenge dosing with ARCOSOLV® DPnP, there were no significant dermal reactions in the Test or the Naive Control Groups. The Incidence Index for the Test Group was 0% (0/20) following challenge dosing.

Under the conditions of this study, ARCOSOLV® DPnP was a non-sensitizer in albino guinea pigs.