Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from Nov. 20, 2001 to Jan. 28, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed according to test guideline in compliance with GLP with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, this study is used for read-across thus avoiding duplicate tests.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
FAT 41030/A
IUPAC Name:
FAT 41030/A
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
FAT 41'030/A

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
male
Details on test animals and environmental conditions:
Test system Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)
Rationale Recognized by the international guidelines as a recommended test system (e.g. OECD, EEC).
Source RCC Ud, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
Number of animals for main study / pretest: 15 males / 3 males
Age at pretest startlbeginning of acclimatization period : 4 - 6 weeks
Body weight at pretest start : Pretest groups: 429 - 437 9
Body weight at beginning of acclimatization period : Control and test group 377 - 444 9
Identification By unique cage number and corresponding ear tags.
Randomization Selected by hand at time of delivery. No computer randomization.
Acclimatization: One week for the control and test group under test conditions after health examination. No acclimatization for the animals of the pretest. Only animals without any visible signs of illness were used for the study.
HUSBANDRY
Room no. 110 / RCC Ud, Füllinsdorf
Conditions: Standard Laboratory Conditions
Accommodation :Individually in Makroion type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
Diet Pelleted standard Provimi Kliba 3418, batch nos. 92101 and 93/01, guinea pig breeding / maintenance diet, containing Vitamin C (Provimi Kliba AG, CH-4303 Kaiseraugst), ad Iibitum. Results of analyses for contaminants are archived at RCC Ud, Itingen.
Water : Community tap water from Füllinsdorf, ad Iibitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ud, Itingen.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Remarks:
PEG300
Concentration / amount:
Intradermal lnduction: 5%
Epidermal lnduction: 50%
Epidermal Challenge: 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG300
Concentration / amount:
Intradermal lnduction: 5%
Epidermal lnduction: 50%
Epidermal Challenge: 25%
No. of animals per dose:
Intradermal Pretest: 1
Epidermal Pretest :2
Control Group :5
Test Group:10
Details on study design:
vehicle:
Identification Polyethylene glycol 300 (PEG 300)
Description colorless viscous liquid
Lot number 412565/1 51301
Source FLUKA Chemie GmbH, CH-9471 Buchs
Stability of vehicle Stable under storage conditions; expiration date: 10-JUL-2002
Storage conditions In the original container, at room temperature (range of 20 ± 3 ℃), away from direct sunlight.
Safety precautions Routine hygienic procedures were used to ensure the health and safety of the personnel.
The vehicle was selected based on preliminary solubility testing which was performed before the study initiation date. Therefore, the formulation trials were excluded from the statement of GLP compliance. The test item was not soluble in purified water but was readily soluble in PEG 300.
AUXILIARY COMPOUNDS: Freund's Complete Adjuvant (FCA), Physiological saline
RATIONALE
The application procedure was used to detect a possible allergenie potential of the test item applied.
READINGS AND SCORING
The scoring system was performed by visual scoring of erythema, oedema and other clinical changes of skin conditions.
SELECTION OF CONCENTRATION OF TEST ITEM FOR MAIN STUDV
Intradermal lnduction:
The 5 % concentration of test item used for the intradermal induction exposure was well-tolerated systemically and was the highest technically applicable concentration.
Epidermal lnduction: The 50 % concentration of test item used for the epidermal induction exposure was well-tolerated systemically and was the highest attainable concentration causing mild skin irritation.
Epidermal Challenge:
The 25 % concentration of the test item used for the challenge application was the maximum tested non-irritant concentration.
MAIN STUDY
1.INDUCTION
1.1 INTRADERMAL INJECTIONS I PERFORMED ON TEST DAY 1
An area of dorsal skin fram the scapular region (appraximately 6 x 8 cm) was clipped free of hair. Three pairs of intradermal injections (0.1 ml/site) were made at the border of a 4 x 6 cm area in the clipped region as folIows:
Test Group: 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
2) The test item, at 5 % in PEG 300.
3) The test item at 5 % in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
Contra I Graup: 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
2) PEG 300
3) 1:1 (w/w) mixture of PEG 300 in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
1.2 EPIDERMAL APPLICATIONS I PERFORMED ON TEST DAY 8
One week after the injections, the scapular area (approximately 6 x 8 cm) was again clipped and shaved free of hair prior to the application. A 2 x 4 cm patch of filter paper was saturated with the test item (50 % in PEG 300) and placed over the injection sites of the test animals.
The amount of test item preparation applied was approximately 0.3 g. The patch was covered with aluminum foil and firmly secured by an elastic piaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The occlusive dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test item.
The guinea pigs of the control group were treated as described above with PEG 300 only, applied at a volume of approximately 0.3 ml.
2 CHALLENGE I PERFORMED ON TEST DAY 22
The test and control guinea pigs were challenged two weeks after the epidermal induction application and were treated in the same way.
Hair was clipped and shaved from a 5 x 5 cm area on the left and right flank of each guinea pig just prior to the application. Two patches (3 x 3 cm) of filter paper were saturated with the test item at the highest tested non-irritating concentration of 25 % (applied to the left flank) and the vehicle only (PEG 300 applied to the right flank) using the same method as for the epidermal application. The amount of test item preparation applied was approximately 0.2 g and a volume of approximately 0.2 ml was used for the vehicle. The dressings were left in place for 24 hours.
Twenty-one hours after removal of the dressing the test sites treated with the test item were depilated as described in the epidermal pretest.
OBSERVATIONS
The following observations and data were recorded during the study:
Viability / Mortality Daily from delivery of the animals to the termination of the test.
Clinical signs (systemic) Daily from delivery of the animals to the termination of the test.
Skin reactions At the times specified during the pretest, induction and challenge periods.
Body weights At pretest and acclimatization start, day 1 and termination of the test.
NECROPSY
No necropsies were performed in the animals of the control and test group sacrificed at termination of the observation period nor in the animals of the intradermal and epidermal pretest sacrificed on test day 1 of the main study.
The animals were sacrificed by intraperitoneal injection of NARCOREN (Rhöne MerieuxGmbH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to 320 mg sodium pentobarbitone/kg body weight) and discarded.














Challenge controls:
no data
Positive control substance(s):
no

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% . No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

SKIN EFFECTS AFTER INTRADERMAL INDUCTION - PERFORMED ON TEST DAY 1

The expected and common findings were observed in the control and test group after the different applications using FCA intradermally. These findings consisted of erythema, oedema, necrotizing dermatitis, encrustation, exfoliation of encrustation and also red dis- coloration produced by the test item. No detailed description of the effects is given in the report as these FCA effects are well- known.

SKIN EFFECTS AFTER EPIDERMAL INDUCTION - PERFORMED ON TEST DAY 8

CONTROL GROUP

No erythematous or oedematous reaction was observed in the animals treated with PEG 300 only.

TESTGROUP

As the test item at 50 % stained the skin red, it was not possible to determine whether erythema was present or not. However, no oedema was observed. The animals were not depilated in the epidermal induction phase.

SKIN EFFECTS AFTER THE CHALLENGE - PERFORMED ON TEST DAY 22

CONTROL GROUP

No skin reactions were observed in the animals when treated with either PEG 300 only or when treated with the test item at 25 % in PEG 300. Red discoloration produced by the test item was noted directly after removal of the patch. To remove the discoloration all animals were depilated 3 hours prior to challenge reading.

TEST GROUP

No skin reactions were observed in the animals when treated with either PEG 300 only or when treated with the test item at 25 % in PEG 300. Red discoloration produced by the test item was noted directly after removal of the patch. To remove the discoloration all animals were depilated 3 hours prior to challenge reading.

VIABILITY / MORTALITY / MACROSCOPIC FINDINGS

There were no deaths during the course of the study, hence no necropsies were performed.

CLiNICAL SIGNS, SYSTEMIC

No signs of systemic toxicity were observed in the animals.

BODY WEIGHTS

The body weight of the animals was within the range commonly recorded for animals of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results given in this study, test item failed to cause skin sensitization in the guinea pigs.
Executive summary:

This study was conducted to assess the cutaneous allergenie potential of FAT 41030/A, the Maximization-Test was performed in 15 (10 test and 5 control) male albino guinea pigs, in accordance with OECD Guideline No. 406. No toxic symptoms were evident in the guinea pigs of the control or test group. No deaths occurred. None of the control and test animals showed skin reactions after the challenge treatment with FAT 41'030/A at 25 % (w/w) in PEG 300.

Based on the above mentioned findings in an adjuvant sensitization test in guinea pigs, FAT 41030/A does not have to be classified and labelled as a skin sensitizer.