Registration Dossier

Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: No data on GLP, comparable to a guideline study
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:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
According to Landsteiner and Jacobs procedure "Studies on Sensitization of Animals with Simple Chemical Compounds", J. Exp. Med. 61:643-656, 1935.
GLP compliance:
not specified
Type of study:
other: Intradermal sensitization test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The analytical report submitted with the sample indicated that the purity of the test material was 96.12%. The test material also contained (by weight) 2.44% 2-nitropropane, 0.64% 1-nitro-2-methyl propane, 0.42% 2-nitrobutane, 0.35% 2-nitro-2-methyl propane, and 0.013% water. Other minor impurities were not listed.

Prodution lot number 9A17-7B

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
Body weights 250-300 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
5% and 1% solutions of test material in saline
Challengeopen allclose all
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
5% and 1% solutions of test material in saline
No. of animals per dose:
10/group
Details on study design:
Thirty male guinea pigs (250-300 g) were divided into 3 groups of 10 each. The animals' backs and flanks were shaved free of hair. One group was intradermally injected with 0.05 ml of a 5% solution of test material in saline. The second group (positive control) was similarly injected with 0.05 ml of a 0.3% dinitro-chlorobenzene (DNCB) solution that was solubilized in a minimum volume of alcohol and made to volume with saline. The third group (negative control) was injected with 0.05 ml of saline. After 24 hours, the injected sites were scored for erythema and edema according to the method of Draize (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Association of Food and Drug Officials of the United States, p.48, 1957). at 48 hours the animals were again injected with 0.1 ml of their respective solutions. The injections were repeated 2-3 times a week until 10 injections were made.

The animals were allowed to rest for 2 weeks after the last injection. On the first day of the third week (or the 43nd day after the first injection), the animals in each group were challenged intradermally with 0.1 ml of solution at a new site. Animals from the first, second and third groups were challenged with 1% test material, DNCB solution (0.03% and 0.3%), and test material and both DNCB solutions (at different sites), respectively. After 24 hours, the injected sites were depilated with "Nair". The injected sites were scored for erythema and edema 3 hours after hair removal. The sites were rescored at 48 hours.

The test material was considered a sensitizer if the number of animals exhibiting skin reactions was higher in Group 1 than in the negative control group. The positive control group was an internal control for the test.
Challenge controls:
Yes, dinitro-chlorobenzene
Positive control substance(s):
yes
Remarks:
dinitro-chlorobenzene

Study design: in vivo (LLNA)

Concentration:
Not applicable
No. of animals per dose:
Not applicable
Details on study design:
Not applicable
Statistics:
None

Results and discussion

Positive control results:
Positive control animals exhibited necrosis during the entire induction period.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
27
Group:
test group
Dose level:
Challenged with 0. 1 ml of 1% solution of test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 27.0. Group: test group. Dose level: Challenged with 0. 1 ml of 1% solution of test material. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Challenged with 0.1 ml of 1% solution of test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Challenged with 0.1 ml of 1% solution of test material. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
27
Group:
positive control
Dose level:
Challenged with 0.1 ml of 0.3 % solution of DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 27.0. Group: positive control. Dose level: Challenged with 0.1 ml of 0.3 % solution of DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Challenged with 0.1 ml of 0.3% solution of DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: Challenged with 0.1 ml of 0.3% solution of DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
27
Group:
positive control
Dose level:
Challenged with 0.1 ml of 0.03% solution of DNCB
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 27.0. Group: positive control. Dose level: Challenged with 0.1 ml of 0.03% solution of DNCB. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Challenged with 0.1 ml of 0.03% solution of DNCB
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: Challenged with 0.1 ml of 0.03% solution of DNCB. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
27
Group:
negative control
Dose level:
Challenged with 0.1 ml of 1% solution of test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 27.0. Group: negative control. Dose level: Challenged with 0.1 ml of 1% solution of test material. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenged with 0.1 ml of 1% solution of test material
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Challenged with 0.1 ml of 1% solution of test material. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Challenged with 0.1 ml of 0.3% solution of DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Challenged with 0.1 ml of 0.3% solution of DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenged with 0.1 ml of 0.3% solution of DNCB
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Challenged with 0.1 ml of 0.3% solution of DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
27
Group:
negative control
Dose level:
Challenged with 0.1 ml of 0.03 % DNCB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 27.0. Group: negative control. Dose level: Challenged with 0.1 ml of 0.03 % DNCB. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Challenged with 0.1 ml of 0.03% solution of DNCB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Challenged with 0.1 ml of 0.03% solution of DNCB. No with. + reactions: 0.0. Total no. in groups: 10.0.

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

During the induction phase, the first 3 injections of a 5% solution of test material caused necrosis.  Therefore, the last seven injections were made with 1%.  Whether or not any reactions were observed at this concentration was not listed.   Positive control animals exhibited necrosis during the entire induction period.

None of the animals that were induced with test material reacted after challenge with the test material.
  In the positive control group 8/10 animals challenged with 0.03% DNCB and all animals challenged with 0.3% DNCB had skin reactions at 27 hours. At 48 hours, all positive control animals injected with 0.3% DNCB and none of the positive controls injected with 0.03% DNCB had positive reactions.   All negative controls challenged with 0.3% DNCB had skin reactions at 27 and 48 hours, and none of the negative controls challenged with 0.03% DNCB had skin reactions at 27 and 48 hours.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
None of the animals that were induced with test material reacted after challenge with the test material. 1-Nitropropane is considered to be not sensitizing.
Executive summary:

None