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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 May 1979 to 22 June 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Follows recommended test procedure. No reference to GLP status in the report.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: J. E. V. Buehler, "Delayed Contact Hypersensitivity in the Guinea Pig", (Arch. Dermat. 91, 171-175, 1965).
Deviations:
not specified
GLP compliance:
no
Type of study:
Buehler test
Justification for non-LLNA method:
Historical Buehler test data available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
TVCI B-5909 .is a white powder.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
The animals used in this study were received from Murphy Breeding Laboratories, Inc. (Hartley albino strain). The animals were maintained on medicated water containing 4% of sulfaethoxypyridazine (6.25% S.E.Z®, American Cyanamid) for four days. A t the end of this period they were furnished with non-medicated water ad libitum; Purina Guinea Pig Chow was available ad libitum throughout the study. The animals were housed singly in wire mesh cages suspended above the droppings throughout the study, and were kept under a 12-hour light/12-hour dark cycle. The animals were of a size that would easily fit into the restrainers used throughout the study.
The animals were acclimated to the laboratory for a t least four days before they were used. Direct identification of the animals by tagging or banding was not done, as this would interfere with the purpose of the study. Careful checking of cage cards and numbering of restraining materials was used to assure the identity of each animal.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol/water (80:20)
Concentration / amount:
0.4 ml of 50% TVCI B-5909 (w/w in 80% ethanol/20% water).
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol/water (80:20)
Concentration / amount:
0.4 ml of 50% TVCI B-5909 (w/w in 80% ethanol/20% water).
No. of animals per dose:
For the sample tested, a group of 30 guinea pigs was used. The group of 30 was divided into 20 guinea pigs which served as test animals throughout the study and 10 guinea pigs which served as controls. The latter animals were maintained without treatment until primary challenge application.
Details on study design:
The upper left quadrant of the backs of the test guinea pigs was clipped using electric clippers. On the following day the patches were applied using a Parke-Davis Readi Bandage coverlet with 20 x 20 mm Webril swatch moistened with 0.4 ml of TVCI B-5909 as a 50% w/w paste in 80% ethanol/20% water. The guinea pigs were placed in restrainers and rubber dental damming was placed over the animals' backs and secured to the restrainers with clips.
After an exposure period of six hours, the patches were removed and the animals were returned to their cages.
The patches were reapplied to the same site once each week for a total of three applications. 0.4 ml of 50% TVCI B-5909 (w/w in 80% ethanol/20%water) was used for each application. The same site was shaved the day before each application was made.
During the induction phase of the study the test material was applied to four additional guinea pigs to determine the highest non-irritating concentration which could be applied for the primary challenge. For this purpose TVCI 8-5909 was tested as 50%, 25%, lo%, and 5% w/w solutions in acetone.
On the day before applications were made the backs of the guinea pigs were clipped with electric clippers. This provided space to test four concentrations on each guinea pig. On the following day a patch was applied to each animal using 0.4 ml of each test solution and the methods described previously.
On the day following application, the clipped areas were depilated with Neet Cream Hair Remover (Whitehall Laboratories, Inc., New York, N.Y. 10017). The depilatory was allowed to remain on the sites for 15 to 30 minutes and was then washed off with warm (ca. 37°C) tap water.
The patch sites were scored for irritation 6 to 7 hours later.
After a two-week rest period a fresh application site for primary challenge was prepared by clipping the lower left quadrant of the backs of the test and control guinea pigs. On the following day a challenge patch was applied to the site using 0.4 ml of TVCI B-5909 as a 50% w/w solution in acetone and the technique previously described. On the next day the sites were depilated and scored within 2 to 3 hours (24-hour reading).
The sites were scored again for a 48-hour reading without additional depilation.
Challenge controls:
None specified
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Irritative effects noted during the pilot test of TVCI B-5909 included one grade of ± and three grades of 0 as a 50% w/w solution in acetone; four grades of 0 as a 25% w/w solution in acetone; four grades of 0 as a 10% w/w solution in acetone; and four grades of 0 as a 5% w/w solution in acetone.

During the primary challenge of TVCI B-5909 as a 50% w/w solution in acetone reactions noted in the test animals at the 24-hour and 48-hour readings included twenty grades of 0. For the control animals ten grades of 0 were noted a t the 24-hour and 48-hour readings.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
When tested according to the method of Buehler, TVCI B-5909 produced no positive responses in either the test or control animals.
Executive summary:

The purpose of this study was to evaluate the potential of TVCI B-5909 to induce delayed contact hypersensitivity in guinea pigs.

 

When tested according to the method of Buehler, TVCI B-5909 produced no positive responses in either the test or control animals.