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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-09-23 to 1983-10-31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable and well documented study report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
The study does not use the appropriate number of test animals in the treatment group.
Principles of method if other than guideline:
Information pertinent to the guideline followed was not available.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The first-choice method according to REACH Annex VII §8.3, the Murine Local Lymph Node Assay, is known to give false positive results with hydrocarbon substances.

Test material

Constituent 1
Reference substance name:
64742-80-9
Cas Number:
64742-80-9
IUPAC Name:
64742-80-9
Constituent 2
Reference substance name:
Hydrodesulfurised middle distillate
IUPAC Name:
Hydrodesulfurised middle distillate
Details on test material:
Test material (as cited in the study report): API 81-10 (CAS# 64742-80-9)
Physical description: clear yellow liquid
Gravity: 34.9
Nitrogen (ppm): 97
Flash Point (°F): 160
Composition: 48.9% paraffins, 20.2% naphthenes, 30.9% aromatics; consists of hydrocarbons having carbon numbers predominantly in the range of C11 to C25 and boiling in the range of approximately 205°C to 400°C

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, Pennsylvania
- Age at study initiation: young adult, age not specified
- Weight at study initiation: 382 to 506 g
- Housing: individually housed in screen-bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 26°C
- Humidity (%): 42 to 72%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark


IN-LIFE DATES: From: 1983-09-23 To: 1983-10-31

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: undiluted for induction phase, 10% v/v in paraffin oil for challenge phase
Concentration / amount:
Test material was applied neat for the induction phase and at 10% v/v in paraffin oil for the challenge phase. Dosing volume was 0.4 mL for all applications.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: undiluted for induction phase, 10% v/v in paraffin oil for challenge phase
Concentration / amount:
Test material was applied neat for the induction phase and at 10% v/v in paraffin oil for the challenge phase. Dosing volume was 0.4 mL for all applications.
No. of animals per dose:
10 animals
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 exposures
- Exposure period: 3 weeks
- Test groups: 0.4 millilitres of undiluted test material was applied to an adhesive pad (Hilltop Chamber, 25-millimetre diameter) and secured onto the clipped dorsal area (left flank) of the animals with dental dam and elastoplast tape.
- Control group: naive controls did not receive any treatment, vehicle controls were dosed with paraffin oil undiluted at 0.4 millilitres, positive controls were dosed with 2,4-dinitrochlorobenzene at 0.3% w/v in 80% aqueous ethanol at 0.4 millilitres (The third sensitising dose for the positive control was applied to a test site slightly posterior to initial site due to severe irritation).
- Site: clipped dorsal area of the left flank
- Frequency of applications: once per week
- Duration: 6-hour duration after which patches and wrappings were removed and test sites were wiped with wet disposable paper towels
- Concentrations: test material applied neat (100%)


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: two weeks following the third sensitising dose
-Test groups: 0.4 millilitres of 10% v/v test material in paraffin oil was applied to an adhesive pad (Hilltop Chamber, 25-millimetre diameter) and secured onto the clipped dorsal area (right anterior quadrant) of the animals with dental dam and elastoplast tape.
-Control group: naive controls were dosed with the test material mixture in the same manner as the test group, vehicle controls were dosed with paraffin oil undiluted at 0.4 millilitres, positive controls were dosed with 2,4-dinitrochlorobenzene at 0.1% w/v in acetone at 0.4 millilitres
- Exposure period: single-exposure, 6-hour duration after which patches and wrappings were removed and test sites were wiped with wet disposable paper towels
- Site: naive site on the clipped dorsal area on the right flank; test sites were treated with depilatory for 20 minutes at 3 hours before the first reading
- Concentrations: 10% v/v in paraffin oil
- Evaluation (hr after challenge): 24 and 48 hours after challenge dose
Challenge controls:
positive controls
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene (0.3% in 80% aqueous ethanol)

Results and discussion

Positive control results:
All 20 animals dosed with 2,4-dinitrochlorobenzene reacted to the material at both the sensitising and challenge phases.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: challenge phase
Group:
test chemical
Dose level:
10% v/v in paraffin oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and oedema scores of 0
Remarks on result:
other: Reading: other: challenge phase. Group: test group. Dose level: 10% v/v in paraffin oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: erythema and oedema scores of 0.
Reading:
other: challenge phase
Group:
negative control
Dose level:
10%v/v in paraffin oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and oedema scores of 0
Remarks on result:
other: Reading: other: challenge phase. Group: other: naive control group. Dose level: 10%v/v in paraffin oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: erythema and oedema scores of 0.
Reading:
other: challenge phase
Group:
positive control
Dose level:
0.1% in acetone
No. with + reactions:
20
Total no. in group:
20

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No dermal irritation was observed in either the test group or naive control group following challenge with 10% v/v test material in paraffin oil. Test material is considered non-sensitising to rabbit skin.
Executive summary:

In a dermal sensitisation study using test material (hydrodesulfurised middle distillate), young-adult, male albino guinea pigs were tested using a closed-patch technique. Dermal irritation ranged form very slight to well-defined erythema and oedema during the sensitising phase with undiluted test material. No dermal irritation was observed in either the test group or naive control group following challenge with 10% v/v test material in paraffin oil. Test material is considered non-sensitising in the guinea pig.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it does not use the appropriate number of test animals in the treatment group, but otherwise, it is a well-conducted, scientifically sound study.