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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Development and Validation of an Alternative Dermal Sensitization Test : The Mouse Ear Swelling Test (MEST)
Author:
Gad S.C., Dunn B.J., Dobbs D.W., Reilly C., Walsh R.D.
Year:
1986
Bibliographic source:
Toxicol. Appl. Pharmacol. 84, 93-114.

Materials and methods

Principles of method if other than guideline:
Not reported
GLP compliance:
no
Type of study:
mouse ear swelling test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
propan-1-ol
Analytical purity: > 98 %.

In vivo test system

Test animals

Species:
mouse
Strain:
CF-1
Sex:
female
Details on test animals and environmental conditions:
- Age at study initiation: 6-8 weeks
- Housing: 5/cage
- Diet: ad libitum, (Purina Rodent Laboratory Chow 5001)
- Water: ad libitum
- Aclimation: 7 days (during this period, any animal with red or swollen ear disqualified and was removed from the study)

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction: 100%
Challenge: 100%

Basis of selection: Based on solubility of n-propanol
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction: 100%
Challenge: 100%

Basis of selection: Based on solubility of n-propanol
No. of animals per dose:
Test groups: 10
Irritation control: 5
Details on study design:
PRELIMINARY RANGE FINDING TEST

- Number of animals: 2/concentration
- Induction: procedure as described in main study whereby four concentrations were used for induction; no further information
- Challenge: each group was challenged at a different concentration; no further details given
- Evaluation: 24 h after challenge
Results: Concentrations utilized in the main study was the highest with minimal iiritation or non-iiritating to the stomach (for induction) and nonirritating to the ear (for challenge)

MAIN STUDY

IRRITATION CONTROL ANIMALS
INDUCTION EXPOSURE:
- Site of application: Abdomen
- Shaved: yes, before application on Day 0
- FCA (Freund's Complete Adjuvant) pretreatment: Yes, injected intradermally 2x á 0.05 ml after which the abdominal skin was then tape stripped.
- Volume: it is unclear from reporting if control animals were induced with a control substance or not, since test substance was applied undiluted (unchanged)
- Repeation: Yes, tape stripping and topical induction applications were repeated for additional 3 consecutive days

CHALLENGE
- Time schedule: 7 days after induction
- Area of application: left ear, (test substance); right ear (treatment unclear; untreated or if treated what solvent was employed)
- Volume applied: 20 µl
- Concentration: undiluted (100%)
- Evaluation: 24h and 48h after challenge
- Anesthesia: Yes, ether before measurement

TEST GROUP
INDUCTION EXPOSURE:
- Site of application: Abdomen
- Shaved: yes, before application on Day 0
- FCA (Freund's Complete Adjuvant) pretreatment: Yes, injected intradermally 2x á 0.05 ml after which the abdominal skin was then tape stripped.
- Volume (Test substance): 100µl applied topically to the center of the shaved region. Area dried with electric dryer
- Concentration: undiluted (100%)
- Repeation: Yes, tape stripping and topical induction applications were repeated for additional 3 consecutive days

CHALLENGE
- Time schedule: 7 days after induction
- Area of application: left ear, (test substance); right ear (treatment unclear; untreated or if treated what solvent was employed)
- Volume applied: 20 µl
- Concentration: undiluted (100%)
- Evaluation: 24h and 48h after challenge
- Anesthesia: Yes, ether before measurement
Positive control substance(s):
yes
Remarks:
Ethylene diamine, dinitrochlorobenzene and p-phenylenediamine

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction 100%; challenge 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction 100%; challenge 100% . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction 100%; challenge 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction 100%; challenge 100% . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
not sensitising