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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Skin sensitivity of the test substance was examined in guinea pigs in accordance with the Guinea Pig Maximization Test.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The system was selected because guinea pigs are often used in skin initation tests and rich basic data are available.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Purity: not reported

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Inc. (3371-8 Koto-cho, Harnamatsu-shi, Shizuoka, Japan)
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 5 weeks
- Weight at study initiation: Mean of 331.8 g with a range of 321 to 342 g
- Housing: Aluminum cages (W 350 mm x D 400 mm x H 230 mm). Animals were kept in groups of 5 or 6 per cage during the quarantine/acclimatization and in a group of 5 per cage during the study period.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days
- Indication of any skin lesions: No

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2°C
- Humidity (%): 50±10%
- Air changes (per hr): 17 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours/day

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: Intracutaneously
Vehicle:
water
Concentration / amount:
0.03, 0.1, 0.3, 1, 3, or 10% solutions
Day(s)/duration:
1 day
Adequacy of induction:
other: Maximum concentration not inducing irritability
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
1, 3, 10, 30, 60, and 100%
Day(s)/duration:
1 day
Adequacy of induction:
other: Maximum concentration not inducing irritability
Challenge
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
Pure solid or 30 and 60% solutions in distilled water
Day(s)/duration:
1 day
Adequacy of challenge:
not specified
No. of animals per dose:
8 (preliminary study), 10 (sensitization group), 5 (control)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: Day 0
- Test groups: 10
- Control group: 5
- Site: lateral abdomen
- Frequency of applications: Single exposure
- Duration: One day
- Concentrations: 20%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 7 and 21
- Exposure period: 48 hours
- Test groups: 10
- Control group: 5
- Site: Site of intradermal injection
- Concentrations: 60%
- Evaluation (hr after challenge): 48

OTHER:RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: Day 0
- Test groups: 4
- Control group: 4
- Site: Intradermal and Closed patch
- Frequency of applications: Single exposure
- Duration: 24 hours
- Concentrations: For intradermal injection: 0.03, 0.1, 0.3, 1, 3, and 10% solutions in physiological saline and for the Closed-patch test, 1, 3, 10, 30, and 60% solutions in distilled water
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1 g of the solid test substance and 0.1 mL of 30 and 60% test substance in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1 g of the solid test substance and 0.1 mL of 30 and 60% test substance in distilled water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 mL of distilled water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1 mL of distilled water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No sensitization was observed in guinea pigs.
Executive summary:

Skin sensitivity of inositol was examined in guinea pigs in accordance with the Guinea Pig Maximization Test. The animals were allocated as follows; 8 animals for the preliminary study, 10 for the sensitization group and 5 for the control group, 23 animals in total.

For sensitization, a: an equal volume emulsion of Freund's complete adjuvant (hereinafter abbreviated as FCA) and physiological saline, b: 10% solution (vehicle: physiological saline), and c: an equal volume emulsion of 20% solution (vehicle: physiological saline) and FCA were administered intracutaneously and 60% solution (vehicle: distilled water) was applied in a closed patch for 48 hours on the intracutaneous injection site on Day 7 of sensitization (treated with Sodium lauryl sulfate on Day 6). The control animals were treated similarly using the distilled water for injection instead of test substance. The animals were challenged on Day 21 after initiation of sensitization by applying 24-hour closed patch of the pure drug substance (white powder) or the 60% or 30% solution of the test substance (vehicle: distilled water) on the lateral abdomen. Skin reactions were observed at 24 and 48 hours after removal of the patch.

Abnormality was absent in either the sensitization group or control group during the study period. No skin reaction was observed with any dosing sample in either the sensitization group or control group. Based on the above results, the test substance was judged to be non-sensitizing to the skin under the condition of this test.