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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study available as unpublished report, restrictions in design and reporting, otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): E000044012
- Clear, pale yellow to yellow-coloured liquid; disagreeable odour
- Specific gravity: AP = 0.87 - 0.91 (H2O = 1 at 39.2°F)
- Flash point: AP = 75°F
- Density: 0.9651 g/mL (as determined by UBTL)
- Analytical purity: no data
- Test material data on file with the study sponsor

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sasco Inc., Omaha, Nebraska, USA
- Sex: 48 males
- Age at study initiation: young adult
- Weight at study initiation: Approximately 300 - 500 g
- Housing: Individually, in stainless steel, wire mesh bottom cages
- Diet: Agway guinea pig feed ad libitum
- Water: ad libitum
- Acclimation period: At least 7 days

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

IN-LIFE DATES: From: 7 February 1990 To: 16 March 1990

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
E000044012 - 1:2 v/v dilution for induction; 1:4 v/v dilution for challenge
DNCB (positive control) - 0.3% for induction; 0.2% for challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
E000044012 - 1:2 v/v dilution for induction; 1:4 v/v dilution for challenge
DNCB (positive control) - 0.3% for induction; 0.2% for challenge
No. of animals per dose:
10 (test, positive control and vehicle control groups)
4 (challenge controls )
Details on study design:
RANGE FINDING TESTS:
- 6 animals used for dose selection (irritation) phase.
- 0.5 mL of undiluted, 1:2, 1:4 and 1:8 v/v applied to shaved dorsal area.
- occlusive dressing
- 6 h application period
- scored after 24 and 48 h

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 0.5 mL of 1:2 v/v dilution
- Control group: 0.5 mL of mineral oil
- Site: dorsal surface
- Frequency of applications: once/week
- Duration: 3 weeks

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) after last induction: 13
- Exposure period: 6 h
- Site: naive site (opposite side of dorsal midline from induction applications)
- Concentrations: 0.5 mL of 1:4 v/v dilution
- Evaluation (hr after challenge):
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
DNCB

Study design: in vivo (LLNA)

Statistics:
Not required

Results and discussion

Positive control results:
Response grades, severity and incidence following challenge exposure to DNCP resulted in a significantly higher response than that seen in the naive challenge control group.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1:4 v/v
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: test group. Dose level: 1:4 v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1:4 v/v
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: test group. Dose level: 1:4 v/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Reading:
1st reading
Hours after challenge:
24
Group:
other: E000044012 challenge control
Dose level:
1:4 v/v
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: E000044012 challenge control
Dose level:
1:4 v/v
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2% DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
well-defined to moderate to severe erythema in all 10 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2% DNCB in 80% ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: well-defined to moderate to severe erythema in all 10 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.2% DNCB in 80% ethanol
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
well-defined erythema in all 10 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.2% DNCB in 80% ethanol. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: well-defined erythema in all 10 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB challenge control
Dose level:
0.2%
No. with + reactions:
2
Total no. in group:
4
Clinical observations:
very slight erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB challenge control
Dose level:
0.2%
No. with + reactions:
2
Total no. in group:
4
Clinical observations:
very slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
mineral oil
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: mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
mineral oil
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: mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
E000044012 was not a delayed contact sensitiser.
Executive summary:
The sensitization potential of E000044012 (CAS 68478-10-4) was investigated in 10 male guinea pigs dermally exposed to a 1:2 v/v dilution of 0.5 mL E000044012 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 E000044012 (CAS 68478 -10 -4) is not a skin sensitiser and no classification is warranted under Dir 67/548/EEC or GHS/CLP.