Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished study report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.

Test material

Constituent 1
Chemical structure
Reference substance name:
Toluene
EC Number:
203-625-9
EC Name:
Toluene
Cas Number:
108-88-3
Molecular formula:
C7H8
IUPAC Name:
toluene
Details on test material:
- Name of test material (as cited in study report): CAS 108-88-3, toluene
- Physical state: colourless liquid
- Lot/batch No.: 623889 543
- Stability under test conditions: stable
- Storage condition of test material: room temperature in the dark
- supplier: Merck, Germany

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL LTD, Basel, Switzerland
- Age at study initiation: approx 6 weeks
- Weight at study initiation: mean 394 g
- Housing: group housing 5 per cage in metal cages with wire mesh floors
- Diet: standard guinea pig diet ad libitum
- Water: ad libitum via automatic system
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.5-23.8°C
- Humidity: 34-92%
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 22 July 1996 To: 15 August 1996

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
10% for intradermal induction, 25 and 50% for challenge
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
10% for intradermal induction, 25 and 50% for challenge
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS: intradermal and epidermal irritancy was investigated to select appropriate concentrations for the main study. The selection was based on absence of toxicity and: for induction (intradermal and epidermal) the highest possible concentration that produced moderate irritation and showed no necrosis; for challenge, the maximum non-irritant concentration. Initial concentrations were selected from the series: undiluted, 50%, 20% and 10%, 5%,

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1 intradermal and 1 epidermal)
- Exposure period: 48 hours for epidermal
- Test groups: Freunds, TS in vehicle, TS in Freunds for intradermal, 0.5 mL TS applied using a Scotchpak-non-woven patch (2 x3 cm) mounted on micropore tape and secured with elastic bandage for epidermal
- Control group: Freunds, vehicle, vehicle in Freunds for intradermal, vehicle for epidermal
- Site: scapular region
- Frequency of applications: intradermal day 1, epidermal day 8
- Concentrations: 10% for intradermal, undiluted for epidermal

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 hours
- Test groups: 0.5mL TS applied using a Scotchpak-non-woven patch (2 x3 cm) mounted on micropore tape and secured with elastic bandage
- Control group: as test
- Site: flank
- Concentrations: 2 (50% and 25%)
- Evaluation (hr after challenge): 24 and 48 hour

Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamicaldehyde

Results and discussion

Positive control results:
Following intradermal induction at 5% in distilled water, epidermal induction with neat test material and challenge with 50% solution all 10 animals responded with a skin reaction greater than control animals.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
none
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
none

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Toluene was not a skin sensitizer in this study.
Executive summary:

A guinea pig maximisation test in accordance with EU guideline B6 (Skin sensitisation) has been carried out. Twenty guinea pigs were intradermally injected with a 10% concentration and epidermally exposed to the undiluted test substance. Ten control guinea pigs were similarly treated, but with vehicle (corn oil) only. Two weeks later all animals were challenged with 50% (maximum non-irritant concentration) and 25% test solution, and vehicle. A single guinea pig showed a grade 1 reaction (discrete or patchy erythema) in response to the 50% solution. No other skin reactions were observed. It was concluded that toluene was not a skin sensitizer in this study. Toluene does not require classification for sensitisation properties.