Registration Dossier

Diss Factsheets

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

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:
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other: GLP compliant, guideline study, available as unpublished study report, no restrictions, fully adequate for assessment
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.
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.
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
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:

There are no specific animal or human data on any of Aliphatics and Cyclics C5 and Higher streams. Data on the specific components benzene, toluene and pentane indicate no dermal sensitisation potential.

Benzene (No classification): Although there are no GLP guideline compliant studies the skin sensitisation potential of benzene was assessed in a mouse ear swelling test (MEST) and a reduced guinea pig maximisation test (GPMT) using neat benzene. None of the mice and none of the guinea pigs showed any evidence of sensitisation (Gad et al, 1986). In a study using 25 male volunteers a maximisation test with induction using 50% benzene and challenge with 20% benzene no evidence of skin sensitisation was seen (0/25) (Kligman, 1966).

Toluene (No classification): 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.

Pentane (No classification): In a guinea pig maximisation test with n-pentane no signs of dermal irritation were recorded during the study and it was concluded that n-pentane showed no sensitisation potential (Exxon Biomedical Sciences, Inc., project no. 196221, 1991).


Migrated from Short description of key information:
No specific sensitisation data are available on any of the streams within this category (CAS Numbers; 102110-14-5, 64741-84-0, 64742-49-0, 68476-55-1, 68956-55-8, 92128-65-9). However there are data on specific components that are present in some streams which indicate that Aliphatics and Cyclics C5 and Higher streams are unlikely to be skin sensitisers.

Justification for selection of skin sensitisation endpoint:
Results from testing the marker substances present in these streams indicate no potential to induce or elicit skin sensitisation. Information available for the key component toluene is considered indicative of the overall skin sensitisation potential of these streams.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No specific animal or human data have been found with regard to respiratory sensitisation for any components within this stream.


Migrated from Short description of key information:
No data have been found concerning respiratory sensitisation and there are no indications that components within this stream are respiratory allergens.

Justification for classification or non-classification

There are no studies on the streams identified for this category but there are sufficient data on constituents to indicate that Aliphatics and Cyclics C5 and Higher streams are not skin or respiratory sensitisers and no classification is warranted for these end-points under Reg (EC) 1272/2008.

Categories Display