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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:
unknown
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A maximisation test was performed based on the current test guidelines but GLP and test guideline are not mentioned

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: no guideline mentioned
Deviations:
no
Principles of method if other than guideline:
The testing was conducted in accordance with the Nakamura et al. improved method (1994) for the Magnusson and Kligman GPMT (1996). This method consists of sensitization exposure using intradermal injection and epicutaneous application, along with challenge exposure to challenge an immunological response (onset of erythema or edema) in the treatment site through reapplication after a certain period of time
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Details on test material:
4,4′-thio-bis(3-methyl-6-tert-butylphenol)
(TBMBP: CAS No. 96-69-5, Nocrac 300 (manufactured by Ouchi Shinko Chemical Industrial))
Purity: Unknown.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Five-week old Std:Hartley strain female guinea pigs (clean) were purchased from Japan SLC, Inc. for the GPMT, and were used for the test after one week of acclimatization. Animals that had no abnormalities in general status or the skin at the administration site on the day before administration were selected and divided randomly into groups. The guinea pigs were freely given solid feed RC-4 (manufactured by Oriental KK) and tap water during both the acclimatization period and the test period. They were kept in an animal room at a temperature of 23 ± 2°C with lights on from 7:00 AM to 7:00 PM

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
olive oil
Concentration / amount:
Multiple concentrations were tested, the most relevant for interpretation:
Intradermal: 0 (control), 0.5% (experimental)
epidermal induction: 0 (control), 25% (experimental)
Challenge: 0 and 5%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Multiple concentrations were tested, the most relevant for interpretation:
Intradermal: 0 (control), 0.5% (experimental)
epidermal induction: 0 (control), 25% (experimental)
Challenge: 0 and 5%
No. of animals per dose:
10 experimentals and 5 controls per group
Details on study design:
A skin irritation study was carried out for each test substance (intradermal administration, sealed patch, open application), the maximum concentrations that could be used in each process were determined, and a preliminary test of skin sensitization was performed.
The following groups were established: A group for which the maximum dosage that could be applied was used for primary sensitization and secondary sensitization (high dosage group), a group for which 1/10,000 of the primary sensitization concentration used for the high dose group was used for primary and secondary sensitization (low dosage group), and, in order to study whether or not skin sensitization was established by the sec-ondary sensitization procedure only, a group for which the first sensitization concentration was set at 0% (solvent administered) and the secondary sensitization concentration was set at the concentration used in the high dose group (sealed patch group), and a control group. The number of animals used in each group was five. In the results of this test, positive reactions were observed for TBMBP in the high dosage group.
Based on the results of the test described above, the dose responsiveness of TBMBP was studied, which was conjectured to have skin sensitization. The dosages, challenge concentrations (open application), and numbers of animals used in the tests are indicated above. A non-sensitization group, which was administered the solvents for each test substance in the skin sensitization test, was provided.

Emulsified solutions of TMCBDPB and HMBCDPB were prepared at the time of use during primary sensitization by taking a Pharmacopoeia olive oil solution or suspension at the prescribed concentrations and by dissolving or suspending these test substances in FCA such that the concentration wouldbe 2 times higher, after which the material was mixed with the equivalent amount of physiological saline solution. Since there was moderate skin irritation for all of the test substances, it was alleviated by treatment with 10% sodium lauryl sulfate (SLS) Vaseline ointment. The evaluation of the skin reaction was determined forty-eight and seventy-two hours after the challenge exposure.
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

Positive control results:
The DNCB positive control revealed positive results:
A skin sensitization test of DNCB, which was the positive control substance, was performed in parallel. The mean evaluation points after forty-eight hours of challenge were 0.8 for challenge concentrations of 10 ppm, 4.0 for 100 ppm, and 5.2 for 1,000 ppm. These results confirmed that favorable skin sensitization reactions were shown to the positive control substance in the lot of guinea pigs used in these tests.
The sensitization rate was not specified in this report.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
5%
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 5%. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
The relative challenge strength of TBMPM as found based on the dose responsiveness of skin reaction (mean evaluation points) and challenge concentration in the 0.5% sensitization group was calculated to be 0.9. DNCB, which was used as a positive control, is a compound representative of skin sensitizing substances, but its relative challenge strength was calculated to be 13.0. It is considered that, when these values are compared, TBMBP is a more weakly sensitizing substance than DNCB.