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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
Since March 9,1994 - May 20,1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, test procedure in accordance with OECD406 methods, meets generally accepted scientific principles, acceptable for assessment. Not GLP compliment. Justification for Read Across will be provided in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was run before the LLNA method was available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: blue powder
- Expiration date of the lot/batch: 2018
- Stability under test conditions: 6 years
- Storage condition of test material: room temperature, not direct light exposure
- Lot/batch No.: JC0236JC

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Company distributed by Anlab s.r.o.
- Weight at study initiation: 302-364 g
- Housing: Guinea pigs were housed in separate cages in plastic cages type T4. The group of 5 animals were housed in one cage.
- Diet : Experimental animals were fed with a standard granulated feed mixture TM produced commercially in Kocanda. Animals were fed ad libitum. Raw material composition provided full biological and nutritional diet for experimental animals
- Water: guinea pigs were supplied with safe drinking water, according to CSN 757111 and each animal additionaly received 20 mg of sorbic acid per day.
- Acclimation period: at least 1 week
Regular cleaning and disinfection of cages was performed to prevent contamination of pathogens according to standard operating procedure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° C ± 3°C
- Humidity (%): 50% ± 15%
- Photoperiod: 12-hour light cycle

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
0,5 % of the tested substance in water solution
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0,5 % of the tested substance in water solution
No. of animals per dose:
Experimental group: 20 females x dose (0,5% )
Control group: 10 females x dose
Details on study design:
A. INDUCTION: INTRADERMAL INJECTION
Day 0- treated group:
Three pairs of intradermal injections of 0,1 ml volume were applied to the shaved area .
injection 1: a 1:1 mixture FCA/water
injection 2: 0,5 % of the test substance in water solution
injection 3: 0,5 % of the test substance in water solution formulated in a 1:1 mixture FCA/water
Day 0- control group:
Three pairs of intradermal injections of 0,1 ml volume were applied to the shaved area .
injection 1: a 1:1 mixture FCA/water
injection 2: water for injection
injection 3: a 50 % w/v formulation of the vehicle in a 1:1 mixture (v/v) FCA/water
INDUCTION: TOPICAL APPLICATION
Day 7- treated group:
Tested area on the neck was again shaved. On the identical site of intradermal injection was applied a filter paper (2x4cm) which was loaded with 25% of tested substance in white vaseline and held in contact by an occlusive dressing for 48 hours.
Day 7- control group:
Tested area on the neck was again shaved. White vaseline was applied to an identical area of intradermal injection on filter paper (2x4 cm) in occlusive dressing for 48 hours.

B. CHALLENGE: TOPICAL APPLICATION
Day 21- treated and control group:
On the right side of the animals was applied a filter paper (2x2 cm) impregnated with 0.5% solution of the tested substance in water for injections, occlusive dressing covered a period of 24hrs. Skin reaction were evaluted on 1, 24, 48 and 72 hours after removal of the patch and cleaning of the challenge area with water. Clinical trials were performed, focusing on the intensity of erythema and edema .


Day 28- treated and control group
second exposure is recommended to avoid false negative results. On the left side of animals was applied a filter paper (2x2 cm) impregnated with 0.5% solution of the tested substance in water for injections, occlusive dressing covered a period of 24hrs. After 1,24,48 and 72 hours was removed the patch and the challenge area was cleaned with water and was carried out a evaluation of the skin reactions.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
1
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 1.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 4.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
1
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 1.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
1
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 1.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
1
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 1.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0,5 % of the tested substance in water
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: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0,5 % of the tested substance in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0,5 % of the tested substance in water. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was tested following OECD 406 for skin sensitisation. No positive skin reactions were observed in the first or in repeated experiments.
Executive summary:
The substance was tested following OECD 406 for skin sensitisation (GMPT). The skin was exposed to maximal concentration of the tested substance and the allergenic potential was determined using the known factors for confirmed contact allergy, such as penetration, skin irritation, and high concentrations.

Induction was performed by intradermal and topical application. Clinical sign (edhema and erythema) were evaluated and no animal showed any important skin reactions after 1, 24, 48 and 72h and it can be concluded that the substance has no allergenic potential.