Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 31 May 1988 to 5 August 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

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)
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XRD-498
- Analytical purity: 99.6%
- Physical state: white powder

- Lot/batch No.: AGR 240043

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston NY

- Weight at study initiation: 340 to 405 g
- Housing:Five per cage
- Diet (e.g. ad libitum): Purina Certified Guinea Pig Chow #5026, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: one week


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 g aliquot of test material was applied under gauze patch
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.4 g aliquot of test material was applied under gauze patch
No. of animals per dose:
10 males per control, and 10 males per 0.4 g dose
Details on study design:
RANGE FINDING TESTS:
A single application of 200 mg of the dry test material was topically applied to the clipped skin or two guinea pigs for 6 hours. Skin irritation readings were recorded 24 and 48 hours later. Based on the restuls of the skin irritation screen, the dry test material was not irritating and was chosen for the study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three
- Exposure period: once per week for three weeks
- Test groups: a 0.4 g aliquot of the test material was applied to the left side of ten guinea pigs under a gauze patch
- Control group: 10% solution of DER 331 epoxy resin in diproplylene glycol monomethyl ether was used as a positive control and applied in a similarmanner in Hill Top Chambers.
- Site: left side of guinea pig
- Frequency of applications: once
- Duration: 6 hours
- Concentrations: 0.4 g aliquot of test material


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: 2
- Exposure period: 6 hours
- Test groups: a 0.4 g aliquot of the test material was applied to the left side of ten guinea pigs under a gauze patch, then on the next day the application sites were depilated with Neet hair cream remover
- Control group: 10% solution of DER 331 epoxy resin in diproplylene glycol monomethyl ether was used as a positive control and applied in a similarmanner in Hill Top Chambers, then on the next day the application sites were depilated with Neet hair cream remover
- Site: right side of guinea pig
- Evaluation (hr after challenge): 24 and 48 hours after challenge

Challenge controls:
The ten guinea pigs that were used in the induction phase were also used in he challenge phase. A 10% solution of DER 331 epoxy resin in dipropylene glycol monomethyl ether was used as a positive control in the induction phase and applied in Hill Top Chambers. The same guinea pigs were treated in the induction phase with the same substance, except on the right instead of left side of the body. The following day, after the 6 hour challlenge, the application sites were depilated with Neet hair cream remover.
Positive control substance(s):
yes
Remarks:
10% solution of DER 331 epoxy resin in dipropylene glycol monomethyl ether

Study design: in vivo (LLNA)

Statistics:
NDA

Results and discussion

Positive control results:
Challenge application of the positive control caused slight to moderate erythema in seven of ten animals.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.4 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0.4 g
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.4 g. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10% DER 331
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 10% DER 331. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
10% DER 331
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 10% DER 331. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: no information
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: no information

Any other information on results incl. tables

Individual Animal Dermal Observations
Treatment Group Animal Number Induction Dermal Response Response
1 2 3 24 hours after challenge 48 hours after challenge
Treatment: 400 mg XRD-498 88A2873 0 0 0 0 0 -
88A2874 0 0 0 0 0 -
88A2875 0 0 0 0 0 -
88A2876 0 0 0 0 0 -
88A2877 0 0 0 0 0 -
88A2878 0 0 0 0 0 -
88A2879 0 0 0 0 0 -
88A2880 0 0 0 0 0 -
88A2881 0 0 0 0 0 -
88A2882 0 0 0 0 0 -
Control: 10% DER 331 88A2883 0 0 0 1 2 +
88A2884 0 0 0 0 1 +
88A2885 0 0 0 1 2 +
88A2886 0 0 0 0 1 +
88A2887 0 0 0 1 1 +
88A2888 0 0 0 0 0 -
88A2889 0 0 0 0 0 -
88A2890 0 0 0 0 0 -
88A2891 0 0 0 0 1 +
88A2892 0 0 0 0 1 +

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Challenge application of XRD-498 caused no reaction in any of the animals. Under the conditions of this study, XRD-498 did not cause delayed contact hypersensitivity in guinea pigs.
Executive summary:

XRD-498 was evaluated for dermal sensitization potential using a modified Buehler method. Ten male Hartley albino guinea pigs received three applications of XRD-498 during the induction phase of the study. A positive control group recieved three applications of 10% DER 331 epoxy resin during the induction phase. The respective groups were challenged with XRD-498 or 10% DER 331 two weeks after the last induction application. The condition of the test sites was assessed approximately 24 and 48 hours after the challenge application. Challenge application of the positive control caused slight to moderate erythema in seven of ten animals. It was therefore concluded that, under the conditions of this study, XRD-498 did not cause delayed contact hypersensitivity in guinea pigs.