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Description of key information

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Skin sensitisation

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Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, restrictions in design and reporting but otherwise adequate for assessment
Qualifier:
according to
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Deviations:
yes
Remarks:
only 10 animals in test group
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska, USA.
- Age at study initiation: Young adult
- Weight at study initiation: 300-500 g
- Housing: Individually in stainless steel, wire mesh bottom cages.
- Diet: Fresh Agway Certified Guinea Pig Feed ad libitum
- Water: ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64-79°F
- Humidity: 40-70%
- Air changes: At least 10/hour
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 7 February 1990 To: 16 March 1990
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: 1:2 v/v dilution,
Challenge: 1:4 v/v dilution
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: 1:2 v/v dilution,
Challenge: 1:4 v/v dilution
No. of animals per dose:
10 test, 10 vehicle control, 10 positive control (plus 4/group challenge control)
Details on study design:
RANGE FINDING TESTS: 6 guinea pigs exposed to neat, 1:2, 1:4 and 1:8 v/v dilutions in mineral oil. 0.5 mL applied for 6 hours and irritation assessed using the Draize scoring system approximately 24 and 48 hours after treatment. No irritation was seen at the 24 hour reading. At the 48 hour reading erythema and oedema were present at the neat site, oedema was present at the 1:2 dilution site and no signs of irritation were seen at the 1:4 and 1:8 v/v dilution sites. Dilutions of 1:2 and 1:4 for the induction and challenge applications, respectively, were selected for use in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours, once per week
- Test groups: 0.5 mL of a 1:2 v/v dilution of E000144700 in mineral oil
- Control group: 0.5 mL of mineral oil
- Site: shaved dorsal area
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after last induction application
- Exposure period: 6 hours
- Test groups: 0.5 mL of a 1:4 v/v dilution of E000144700 in mineral oil
- Control group: 0.5 mL of a 1:4 v/v dilution of E000144700 in mineral oil
- Site: naive site on the shaved dorsal area
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
Unused naive guinea pigs were used to distinguish between "background" irritation and actual allergic response (4 guinea pigs for each group-test, vehicle control and positive control)
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Following induction (x3) with 0.3% DNCB, challenge with 0.2% DNCB resulted in significantly higher response than that observed in the naive challenge control group.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1:4 v/v dilution . No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: no response.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1:4 v/v dilution . No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: no response.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1:4 v/v dilution . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1:4 v/v dilution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1:4 v/v dilution . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema scores of 1 or 2 in all animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2% . No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: erythema scores of 1 or 2 in all animals.
Interpretation of results:
other: Not sensitising
Conclusions:
Under the conditions of the study described, E000144700 was not a delayed contact sensitiser.
Executive summary:

The sensitization potential of E00014470 (CAS 68516-20-1) was investigated in male guinea pigs dermally exposed to a 1:2 v/v dilution of 0.5 mL E000144700 in mineral oil for each of 3 induction phases. Following challenge with a 1:4 dilution response grades, severity and incidence were not greater than those at the control group site. The positive control, DNCB, produced significantly higher responses than in the control group which were free of dermal lesions throughout the study period.

It is concluded that E000144700 (CAS 68516-20-1) is not a skin sensitiser and no classification is warranted under Dir 67/548/EEC or GHS/CLP.

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

Skin sensitisation

Non-human information

In a study using methodology based on Buehler, the sensitization potential of CAS 68516-20-1 was investigated in groups of 10 male guinea pigs dermally exposed to a 1:2 v/v dilution of 0.5 mL in mineral oil for each of 3 induction phases. Following challenge with a 1:4 dilution response grades, severity and incidence were not greater than those at the control group site. It was concluded that CAS 68516-20-1 was not a skin sensitiser.

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 low benzene naphtha streams or toluene NOTOX (1996). Assessment of contact hypersensitivity to toluene in the albino guinea pig (Maximization test). Testing laboratory: NOTOX, s'Hertogenbosch, The Netherlands. Report no.: 179911. Owner company: Shell. Report date: 1996-11-21.


Migrated from Short description of key information:
The available animal data are sufficient to conclude that members of the low benzene naphtha category are not skin sensitisers. Toluene is not a skin sensitiser in animals and there are no reports of skin sensitisation attributed to toluene in humans.

Justification for selection of skin sensitisation endpoint:
Data for representative streams, together with information on the key marker substance toluene, indicate that members of this category will not cause skin sensitisation.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No animal or human data have been found with regard to respiratory sensitisation of low benzene naphtha streams or of the specific component, toluene.


Migrated from Short description of key information:
There are no data on respiratory sensitisation for the low benzene naphtha streams or toluene, but there is no evidence that they require classification for sensitisation properties.

Justification for classification or non-classification