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Toxicological information

Endpoint summary

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Administrative data

Description of key information

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

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other: GLP compliant, guideline study, available as unpublished study report, no restrictions, fully adequate for assessment
Reason / purpose for cross-reference:
read-across: supporting information
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
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:

Skin sensitisation

There are no specific animal or human data on any of Aliphatics and Cyclics C5 and Higher streams. Data on the specific constituents 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).

In relation to cyclohexane skin irritation, although the animal studies gave results slight below the limits of classification, the RAR (2004) concluded that it had been demonstrated that the irritant properties of cyclohexane were delayed and persisted until the end of observation period (16 days). Since defatting properties are also expected, it was concluded that cyclohexane should be classified.

To assess skin sensitisation of cyclohexane, a modified Buehler test was performed by White Eagle Toxicology Laboratories (1996) (method B6 Annex V and according to EC and OECD GLP). During the induction phase, the response ranged from no redness (14/20 animals) to very faint redness on some tested animals. A very faint redness was observed 24 hours after the challenge application in 1/20 tested animals, no reactions were observed in other tested animals or negative controls. There was no incidence of sensitisation among cyclohexane induced and challenged animals

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 constituent 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 constituents within this stream.

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.