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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
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other: GLP compliant, guideline study, available as unpublished study report, no restrictions, fully adequate for assessment
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:
The guinea pig maximisation test (GPMT) used to support the sensitisation endpoint is of good quality and provides clear results, therefore the preferred murine local lymph node assay (LLNA) was not performed to avoid unnecessary animal testing.
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
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
10% for intradermal induction, 25 and 50% for challenge
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
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.
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.
Group:
negative control
Dose level:
25% and 50%
Remarks on result:
other: No skin reactions were evident in response to the 50% and 25% concentration in the control animals
Group:
positive control
Dose level:
50% concentration
Remarks on result:
other: Skin reactions observed in response to 50% positive control concentration in the challenge phase lead to a sensitisation rate of 100%
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

LOA is currently reviewing the human and animal data supporting Human Health for Toluene. It is expected to be completed by Q4 2020.

Non-human information

A maximisation test in accordance with EU guideline B6 (Skin sensitisation) was performed by NOTOX (1996) to assess the sensitisation potential of toluene in guinea pigs. A grade 1 reaction (discrete or patchy erythema) was seen in 1/20 tested animals in response to challenge with a 50% solution. No other skin reactions were observed. It was concluded that toluene was not a skin sensitiser in this study.

Human information

There are no reports of skin sensitisation in humans attributed to toluene.


Migrated from Short description of key information:
The available animal data are sufficient to conclude that toluene is not a skin sensitiser. This is supported by the lack of human case reports for this high tonnage and widely used material.

Justification for selection of skin sensitisation endpoint:
Results from a guideline study provide no evidence of a potential to induce or elicit skin sensitisation

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

No data animal or human data have been found with regard to respiratory sensitisation.


Migrated from Short description of key information:
No data have been found concerning respiratory sensitisation and there are no indications that toluene is a respiratory allergen.

Justification for selection of respiratory sensitisation endpoint:
No data have been found concerning respiratory sensitisation and there are no indications that toluene is a respiratory allergen

Justification for classification or non-classification

The animal data supported by the lack of human case studies reporting skin or respiratory sensitisation allow for the overall conclusion that, according to the GHS / CLP criteria, toluene does not require classification for sensitisation properties.