Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP and acc. to OECD guideline no. 406

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In vivo study that was performed before 10 May 2017

Test material

Constituent 1
Chemical structure
Reference substance name:
Nadide
EC Number:
200-184-4
EC Name:
Nadide
Cas Number:
53-84-9
Molecular formula:
C21H27N7O14P2
IUPAC Name:
nadide
Test material form:
other: crystalline powder
Details on test material:
- Physical state: crystalline powder
- Analytical purity: 98-area%
- Storage condition of test material: 2 - 8 °C, protected from light

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl:HA - Guinea Pigs
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 4 weeks
- Weight at study initiation: 353- 399 g
- Housing: Semi barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 oc
- Humidity (%): 55+/- 10%
- Air changes (per hr): at least I 0 x I hour
- Photoperiod (hrs dark / hrs light) :Artificial light, sequence being 12 hours light, 12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline
Concentration / amount:
2.5% and 50%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
2.5% and 50%
No. of animals per dose:
Number of animals in the test group: 10
Number of animals in the negative-control group: 5
Number of animals in the dose range finding study: 3
Details on study design:
RANGE FINDING TESTS:
For the justification of dose levels a preliminary test was performed.
1 animal was treated intradermally with concentrations of 5% and 2.5% of the test item (dissolved in physiological saline 0.9% NaCl)
1 animal was treated topically with concentrations of 50% and 25% of the test item (suspended in vaseline), for 24 hours.
1 animal was treated topically with concentrations of 50% and 25% of the test item (suspended in vaseline), for 48 hours.
MAIN STUDY
A. INDUCTION EXPOSURE
induction: First Stage, lntradermal lnjection
Three pairs of intradermal injections of 0.1 mL volume were given in the shoulder region which was cleared of hair by clipping so that one of each par lies on each side of the midline.
Test Group: Day 0
Injection I: a I: I mixture (v/v) FCA/physiological saline 0.9% NaCl
Injection 2: 2.5% the test item in physiological saline 0.9% NaCl
Injection 3: 2.5% the test item formulated in a I :I mixture (v/v) FCA/physiological
saline 0.9% NaCl
Control Group: Day 0
Injection I: a I: I mixture (v/v) FCA/physiological saline 0.9% NaCI
Injection 2: 100% physiological saline 0.9% NaCl
Injection 3: a 50% (v/v) formulation of physiological saline 0.9% NaCl in a 1:1 (v/v)
mixture FCA/physiological saline 0.9% NaCl
Injections I and 2 were given close to each other and nearest to the head, while
injection 3 was given toward the caudal part of the test area.
11. 7. Induction: Second Stage, Topical Application
Test Group and Control Group: Day 6
Approximately twenty-four hours before the topical application the test area was
painted with 0.5 g of I 0% sodium Iaury! sulphate in vase line after close clipping in
order to create a local irritation.
Test Group: Day 7
The test item was suspended in vaseline at a concentration of 50%. A patch was fully
loaded with 0.5 g of the prepared test item. Then it was applied to the test area and held
in contact with the help of an occlusive dressing for 48 hours.
Control Group: Day 7
A patch was fully loaded with 0.5 g ofvaseline. Then it was applied to the test area and
held in contact with the help of an occlusive dressing for 48 hours.

B. CHALLENGE EXPOSURE
Challenge: Topical Application
The flanks of treated and control animals were cleared of hair by close-clipping.
Test Group and Control Group: Day 20
The test item was suspended in vaseline at a concentration of 50%. A patch, loaded with
0.5 g of the prepared test item was applied to the left flank of the animals and a patch
loaded with 0.5 g of the vehicle to the right flank (intraspecific control). The patches
were held in contact with the help of an occlusive dressing for 24 hours.
The application area was not rinsed.
OTHER:
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole, purity> 98%

Results and discussion

Positive control results:
The sensitisation rate after application of the positive-control substance mercaptobenzothiazole (15% in vaseline) was IOO%, confirming the reliability of the test system.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
15%
No. with + reactions:
5
Total no. in group:
5

Any other information on results incl. tables

 Challenge Concentrations of Test Substance: 50%
  Number of animals showing skin reaction after:
   24 hours  48 hours
 Test group  0
 Negative-control group
 

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 present study it can be stated that the test item b-Nicotinamide-adenine Dinucleotide II (nadide) caused no reactions
identified as sensitisation at the tested concentration. According to the EC criteria for classification and labelling requirements for dangerous
substances and preparations labelling is not necessary.
Executive summary:

Skin sensitisation potential of Nadide was tested using the Guinea Pig Maximisation Test in accordance with OECD guideline 406.

A preliminary test was used to determine the concentrations to be used. The concentrations chosen for the main test were: 2.5% for the intradermal induction; 50% for the dermal induction and 50% for the challenge concentration. 10 female guinea pigs (Crl:HA) were used as test group and 5 animals in the negative control group. Under the conditions of the present study it can be stated that the test item b-Nicotinamide-adenine Dinucleotide II (nadide) caused no reactions

identified as sensitisation at the tested concentration. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations labelling is not necessary. The substance is also considered unclassified according to GHS.