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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29-02-2000 to 30-03-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to international guidelines.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace animals, Boyertown, PA on 22/2/2000
- Quarantine period of at least six days.
- Age at study initiation: 2 to 3 weeks
- Weight at study initiation: males: 235-322 g
- Fasting period before study: not applied
- Housing: 1/cage
- Diet (e.g. ad libitum): Fresh Purina Rat Chow (Diet #5025)
- Water (e.g. ad libitum): Tap water
- Acclimation period: 1 to 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12
Route:
epicutaneous, occlusive
Vehicle:
other: safflower oil
Concentration / amount:
1. 100% Ceraphyl RMT
2. 5% Ceraphyl RMT in safflower oil
3. 100% Safflower oil
Route:
epicutaneous, occlusive
Vehicle:
other: safflower oil
Concentration / amount:
1. 100% Ceraphyl RMT
2. 5% Ceraphyl RMT in safflower oil
3. 100% Safflower oil
No. of animals per dose:
25
Details on study design:
20 animals per group were tested in the induction and challenging phases, while 5 animals per group were only challenged to serve as a naive control.The site reserved for induction was only clipped in ten animals, while it was abraded in the other ten animals. A volume of 0.4 ml of test substance, mixture of test substance with safflower or safflower only was applied for induction using a 25 mm Hilltop Chamber, which was covered and wrapped to provide full occlusion. Exposure lasted for 6 hours. This procedure was repeated two times with a period of one week between each of the exposures resulting in 3 x 6-h exposures on the same area of skin. Forteen days after the last induction the challenge was performed with the same procedure but using another site on the skin. A significant reaction/incidence = Erythema score ≥ 1.
Challenge controls:
Yes, naive controls of treated animals and vehicle controls.
Positive control substance(s):
yes
Remarks:
Sensitivity of the guina pigs to dinitrochlorobenzene (DNCB) performed every half year.
Positive control results:
24h: incidence was 0.50 and severity was 0.78
48h: incidence was 0.30 and severity was 0.58
Conclusion: DNCB is a sensitizer
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% abraded
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% abraded. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% clipped only
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% clipped only. No with. + reactions: 6.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% abraded
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% abraded. No with. + reactions: 3.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% clipped only
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% clipped only. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
clipped only
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: clipped only. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% abraded
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% abraded. No with. + reactions: 6.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% clipped only
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% clipped only. No with. + reactions: 4.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% abraded
No. with + reactions:
5
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% abraded. No with. + reactions: 5.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% clipped only
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% clipped only. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
abraded
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: abraded. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
clipped only
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: clipped only. No with. + reactions: 0.0. Total no. in groups: 10.0.

Erthema incidences in the Ceraphyl RMT (RMT) treated groups:

100% RMT 24 48 5% RMT 24 48
ma1 1 1 ma1 2 2
ma2 0 0 ma2 1 1
ma3 1 0.5 ma3 1 1
ma4 0.5 0 ma4 0.5 1
ma5 0 0 ma5 0.5 0
ma6 2 1 ma6 0 1
ma7 1 1 ma7 0 0.5
ma8 0 0 ma8 0.5 0
ma9 2 2 ma9 0 0
ma10 0 0 ma10 0 0
Severity 0.75 0.55 Severity 0.55 0.65
Incidence 0.50 0.40 Incidence 0.30 0.50
100% RMT 24 48 5% RMT 24 48
m-1 1 1 m-1 0 0
m-2 0.5 0.5 m-2 0.5 0
m-3 0 0 m-3 0 0.5
m-4 1 1 m-4 0 0
m-5 0.5 0 m-5 0 0
m-6 2 2 m-6 0.5 0.5
m-7 1 1 m-7 0 0
m-8 0.5 0.5 m-8 0 0
m-9 1 1 m-9 + +
m-10 2 1 m-10 1 1
Severity 0.95 0.80 Severity 0.22 0.22
Incidence 0.60 0.60 Incidence 0.10 0.10
ma = abraded
Interpretation of results:
sensitising
Remarks:
Migrated information sub-category 1B Criteria used for interpretation of results: EU
Conclusions:
Ceraphyl RMT is not classified as sub-category 1A ensitizer because no significant incidences (erythema score ≥ 1) were ≥ 60 % at 5% (= between 0,2 % to 20 %) topical induction dose. Ceraphyl RMT meets the criteria for classification as sub-category 1B sensitizer because incidences (erythema score ≥ 1) were between 15 and 60 % for 5 % topical induction on abraded skin and > 15 % at 100 % topical induction dose.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The response after intradermal induction dose of 100% Ceraphyl RMT is > 30 % in a maximization test. Incidences (erythema score ≥ 1) were between 15 and 60 % for 5 % topical induction on abraded skin and > 15 % at 100 % topical induction dose in a Bueler test. Another maximization test showed a responding of > 60 % (100%) at 1 % intradermal induction dose.

A test item is regarded as a sensitizer in the LLNA if the exposure to one or more test concentrations resulted in 3-fold or greater increase in incorporation of HTdR compared with concurrent controls, as indicated by the S.l. In a study included in this dossier, S.I. values of 1.4, 1.9 and 2.9 were determined with the test item at concentrations of 2.5 %, 5 % and 10 % (w/v), respectively, in acetone/olive oil (4/1, vlv). Hence, CERAPHYL® RMT does not show an allergenic potential when tested up to the concentration of 10 % (w/v) in acetone/olive oil (4/1, vlv) in the LLNA. The results indicate that the EC3 is > 10%.

A repeated Insult Patch test (epicutaneous test) in humans showed that an analogue of the substance had no potential for dermal irritation or allergic contact sensitization at a dermal dose of 55 mg/cm2.


Migrated from Short description of key information:
Based on the results of four reliable studies, the substance is to be considered a sub-category 1B skin sensitizer.

Justification for selection of skin sensitisation endpoint:
The result of this test include both 5 and 100% of induction doses.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Ceraphyl RMT is not classified as sub-category 1A sensitizer because no significant incidences (erythema score ≥ 1) were ≥ 60 % at 5% (= between 0,2 % to 20 %) topical induction dose. Ceraphyl RMT meets the criteria for classification as sub-category 1B sensitizer because incidences (erythema score ≥ 1) were between 15 and 60 % for 5 % topical induction on abraded skin and > 15 % at 100 % topical induction dose. This was confirmed in other animal studies.