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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 based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1985/11/18 - 1986/01/03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report in agreement with OECD guideline 406-GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CAMM Research Laboratory Animals, Wayne, NJ 07470
- Age at study initiation: young adults
- Weight at study initiation: 284-331g
- Housing: individually
- Diet (e.g. ad libitum): fresh Certified Purina guinea pig chow #5026, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days, induction phase animals; 7 days, dose selection phase animals

ENVIRONMENTAL CONDITIONS
-Temperature: 64 to 74 degrees F
-Humidity: 29 to 62 percent relative humidity
-Photoperiod: 12hrs dark/12hrs light

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: 0.5 ml, neat
Challenge: 0.5 ml, neat
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: 0.5 ml, neat
Challenge: 0.5 ml, neat
No. of animals per dose:
Dose selection: 6
Induction/challenge: 20
Challenge control: 8
Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 1 (receiving 0.5 ml of undiluted test article)
- Control group: 2 (challenge control and positive control (0.3% DNCB in 80% ethanol/water))
- Site: along a side of the dorsal midline
- Frequency of applications: Weekly
- Duration: Three weeks

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 14 post induction applications
- Exposure period: 6 hours
- Test groups: 1 (receiving 0.5 ml of undiluted test article)
- Control group:2 (Challenge control and positive control (0.2% DNCB in 80% ethanol/water))
- Site: Naive area along a side of the dorsal midline
- Evaluation (hr after challenge): 24- and 48-hours post-application, challenge sites were scored for erythema and edema according to the Draize technique
Positive control substance(s):
yes
Remarks:
2,4 dinitrochlorobenzene (2,4 DNCB)

Results and discussion

Positive control results:
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.

DNCB:
Challenge: 24 h reading: 3.2 (response grade), 10/10 animals
48 h reading: 2.4 (response grade), 10/10 animals

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 mL neat
No. with + reactions:
9
Total no. in group:
9
Clinical observations:
Avg. combined erythema/edema score = 2.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 mL neat. No with. + reactions: 9.0. Total no. in groups: 9.0. Clinical observations: Avg. combined erythema/edema score = 2.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 mL neat
No. with + reactions:
8
Total no. in group:
9
Clinical observations:
Avg. combined erythema/edema score = 0.9
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 mL neat. No with. + reactions: 8.0. Total no. in groups: 9.0. Clinical observations: Avg. combined erythema/edema score = 0.9.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge control
Dose level:
0.5 mL
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
Avg. combined erythema/edema score = 2.0
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control
Dose level:
0.5 mL
No. with + reactions:
4
Total no. in group:
4
Clinical observations:
Avg. combined erythema/edema score = 1.2
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3% DNCB
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test article F-64-01 was not a delayed contact sensitizer and the positive control DNCB was a delayed contact sensitizer.
Executive summary:

Male Hartley Albino guinea pigs were dermally exposed to test article F-64-01 neat at a volume of 0.5 ml for each of three induction phases. For the challenge phase, the test article was administered undiluted for both the induction/challenge and challenge control group animals. Response grades, severity and incidence at the time of the challenge exposure for the test article F-64-01 indicated no dermal responsiveness in the induction/challenge group above that observed in the naive challenge control group. The naive challenge irritation control group animals were also free of any dermal response. 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.

Under the conditions of the test, the test article F-64-01 was not a delayed contact sensitizer and the positive control DNCB was a delayed contact sensitizer.