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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 406 performed under GLP conditions on an analogue substance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The Buehler skin sensitisation test is a scientifically valid method for assessing skin sensitisation potential. As the data exists and is adequate for hazard assessment, performing a new LLNA test is not scientifically justified

Test material

Constituent 1
Reference substance name:
Naphtha (petroleum), light catalytic cracked
EC Number:
265-056-2
EC Name:
Naphtha (petroleum), light catalytic cracked
Cas Number:
64741-55-5
IUPAC Name:
Naphtha (petroleum), light catalytic cracked
Constituent 2
Reference substance name:
Light catalytic cracked naphtha
IUPAC Name:
Light catalytic cracked naphtha

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Induction dose: 0.4 ml, neat
Challenge dose: 0.4 ml, 1:4 dilution in paraffin oil

Positive Control DNCB:
Induction dose: 0.4 ml, 0.3% dilution in 80% aq. ethanol
Challenge dose: 0.1% dilution in acetone
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
Induction dose: 0.4 ml, neat
Challenge dose: 0.4 ml, 1:4 dilution in paraffin oil

Positive Control DNCB:
Induction dose: 0.4 ml, 0.3% dilution in 80% aq. ethanol
Challenge dose: 0.1% dilution in acetone
No. of animals per dose:
4 males for dose-selection
10 males for induction/challenge
10 males for challenge control
10 males for vehicle control group
20 males for positive control group
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Frequency of applications: once per week
- Duration: 3 weeks


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 14 post-induction application
- Exposure period: 6 hours
- Evaluation (hr after challenge): 24 and 48 hrs

OTHER: response grade score = erythema + edema
Challenge controls:
Naive guinea pigs receiving only the challenge dose in order to distinguish between “background” irritation response and actual allergenic response.
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

Positive control results:
DNCB:
Challenge: 24/48 hr average: 2.2 (response grade), 20/20 animals

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
other: Challenge: Avg 24 and 48 hour readings
Group:
test chemical
Dose level:
25% v/v dilution challenge phase
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
0.0 Erythema
0.0 Edema
Remarks on result:
no indication of skin sensitisation
Reading:
other: Sensitizing Phase: Avg 24 and 48 hour readings
Group:
test chemical
Dose level:
100% (applied neat)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
1.8 Erythema Avg
1.4 Edema Avg
Remarks on result:
other: mild irritation
Key result
Reading:
other: Challenge: Avg 24 and 48 hour readings
Group:
positive control
Dose level:
2,4-dinitrochlorobenzene, was administered at a concentration of 0.3% w/v in 80% aqueous ethanol, wit. a dosage volume of 0.4 mL for the sensitizing phase.
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
1.6 Erythema
0.75 Edema
Remarks on result:
positive indication of skin sensitisation
Reading:
other: Sensitizing Phase: Avg 24 and 48 hour readings
Group:
positive control
Dose level:
2,4-dinitrochlorobenzene, was administered at a concentration of 0.3% w/v in 80% aqueous ethanol, wit. a dosage volume of 0.4 mL for the sensitizing phase.
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
2.25 Erythema
1.9 Edema
Remarks on result:
other: Moderate Irritation
Reading:
other: Challenge: Avg 24 and 48 hour readings
Group:
negative control
Dose level:
0.4% Paraffin oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
0.0 Erythema
0.0 Edema
Remarks on result:
no indication of skin sensitisation
Reading:
other: Sensitizing Phase: Avg 24 and 48 hour readings
Hours after challenge:
0
Group:
negative control
Dose level:
0.4% Paraffin oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
0.0 Erythema
0.0 Edema
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Light catalytic cracked naphtha (API 83-20) did not induce a sensitisation response in guinea pigs in this study. This finding does not warrant the classification of the test article as a skin sensitiser under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Male Hartley Albino guinea pigs were dermally exposed to light catalytic cracked naphtha (API 83-20), neat, at a volume of 0.4 ml for each of the three induction phases. For the challenge phase, light catalytic cracked naphtha was administered as a 1:4 dilution in paraffin oil for the challenge and challenge control group animals. Response grades, severity and incidence at the time of the challenge exposure for the test article indicated no dermal responsiveness in the induction/challenge group above that observed in the naive challenge control group. Response grades, severity and incidence at the time of the challenge exposure for DNCB resulted in a significantly higher response in the induction/challenge group than that observed in the naive challenge control group. This finding does not warrant the classification of light catalytic cracked naphtha (API 83-20) as a skin sensitiser under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 

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