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Diss Factsheets

Administrative data

Description of key information

The test substance is not considered as skin sensitiser to rabbit.

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:
21 October 1996 to 26 November 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.
Specific details on test material used for the study:
Identity: FAT 40557/A
Batch-no.: PV1
Purity: 65 %
Appearance: Solid powder, red-brown
Stability of Test Article: Stable under storage condition; expiration date: 30-SEP-2002
Stability of Test Article Dilution: Stable in polyethylene glycol, saline and FCA for at least 48 hours
Expiration date: 30 September, 2002
Storage conditions: In the original container at room temperature away from direct sunlight.
Species:
guinea pig
Strain:
Himalayan
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age at delivery: 5-7 weeks
- Weight at delivery: Control and test group: 291 - 416 g, Pretest: 354-431 g
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Nafag Ecosan 845 25W4, batch nos. 90/96 and 105/96 guinea pig breeding/ maintenance diet ("Nafag", Nähr- und Futtermittel AG, CH-9202 Gossau), ad libitum.
- Water: Community tap water from Itingen, ad libitum.
- Acclimation period: One week for the control and test group under test conditions after health examination. No acclimatization for the animals of the pre-test.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70 (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
5 %; 0.1 ml/site (Three pairs of intradermal injections)
Day(s)/duration:
Day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Concentration / amount:
50 %; 0.3 ml
Day(s)/duration:
Day 8
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50 %; 2 x 2 cm) of filter paper
Day(s)/duration:
Day 22
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Ten females were treated with the vehicle alone and twenty females were treated with the test article.
Details on study design:
RANGE FINDING TESTS:
- Intradermal injections: Two pairs of intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline was made simultaneously into the shaved neck of two guinea pigs. One week later intradermal injections (0.1 mL/site) were made into the clipped flank of the same guinea pigs at concentrations of 5 %, 3 % and 1 % of the test article in polyethylene glycol 400. The resulting dermal reactions were assessed 24 hours later. For intradermal induction application in the main study a 5 % test article dilution was selected.
- Epidermal applications: Two pairs of intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline was made simultaneously into the shaved neck of four guinea pigs. One week later both flanks of each of the guinea pigs were clipped and shaved just prior to the application. Thereafter 4 patches of filter paper ( 2 x 2 cm) were saturated with the test article at 50 % (this concentration used was found to be the most qualified to assure an optimum technical application procedure), 25 %, 15 % and 10 % in polyethylene glycol 400 and applied to the clipped and shaved flanks. The volume of test article concentration applied was approximately 0.2 mL. The patches were covered by a strip of aluminum foil and firmly secured by elastic plaster wrapped around the trunk and covered with impervious adhesive tape. This procedure ensured the intensive contact of the test article. The dressings were removed after an exposure period of 24 hours. 21 hours after removal of the dressing the application site was depilated with an approved depilatory cream (VEET Cream, Reckitt & Colman AG, CH-4123 Allschwil) to clean the application site from staining produced by the test article, so that possible erythema reactions were clearly visible at that time. The depilatory cream was placed on the patch sites and surrounding areas, and left on for 3-5 minutes. It was then thoroughly washed off with a stream of warm, running water. The animals were then dried with a disposable towel, and returned to their cages. The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema on a numerical basis according to Draize.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal injections: An area of dorsal skin from the scapular region (approximately 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 follows: 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline. 2) The test article, diluted with polyethylene glycol 400. 3) The test article diluted to 5% by emulsion in a 1:1 mixture of Freund's complete adjuvant and physiological saline.
Epidermal applications: On test day 7 and approximately 22 hours prior to the epidermal application the scapular area (approximately 6 x 8 cm) of the animals of the control and test group was clipped, shaved free of hair and the test area was pre-treated with a 10 % dilution of Sodium-Lauryl-Sulfate (SLS) in paraffinum per liquidum as no primary irritation had been observed in the pre-test. The SLS was massaged into the skin with a glass rod without bandaging. This 10 % concentration of SLS enhances sensitization by provoking a mild inflammatory reaction. On test day 8, a 2 x 4 cm patch of filter paper was saturated with the test article (50 % in polyethylene glycol 400) and placed over the injection sites of the test animals. The volume of test article concentration applied was approximately 0.3 mL. The patch was covered with aluminum foil and firmly secured by an elastic plaster wrapped around the trunk of the animal and secured with impervious adhesive tape. The dressings were left in place for 48 hours. The epidermal application procedure described ensured intensive contact of the test article. The guinea pigs of the control group were treated as described above with polyethylene glycol 400 only. Reaction sites were assessed for erythema and oedema 24 and 48 hours after removal of the dressing, using the numerical grading system according to Draize.

B CHALLENGE
The test and control guinea pigs were challenged two weeks after the epidermal induction application. The test and control guinea pigs 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 ( 2 x 2 cm) of filter paper were saturated with the highest non-irritating concentration of 50 % (left flank) and the vehicle only (polyethylene glycol 400 applied to the right flank) using the same method as for the epidermal application. The dressings were left in place for 24 hours. Approximately 21 hours after removal of the dressing the test sites treated with the test article were depilated with an approved depilatory cream (VEET Cream, Reckitt & Colman AG, CH-4123 Allschwil). The cream was placed on the patch sites for 3-5 minutes and then washed off with a stream of warm running water. When the application sites were clean and any stains from the test article removed the animals were dried with a disposable paper towel and returned to their cages. Approximately 24 and 48 hours after the removal of the dressing the application sites were assessed for erythema and oedema using the numerical scoring system according to Draize.
Challenge controls:
The control animals were treated in the same way as described above without the test substance.
Positive control substance(s):
yes
Remarks:
The positive controls were performed with 2-Mercaptobenzothiazole (RCC project 901080) from 30 April 1996 to 07 June 1996 and Alphahexylcinnamaldehyde (RCC project 901203) from 14 May 1996 to 21 June 1996.
Positive control results:
Clear positive results were observed in treated animals after the epidermal challenge application of 2-Mercaptobenzothiazole (RCC project 901080) from 30 April 1996 to 07 June 1996 and Alphahexylcinnamaldehyde (RCC project 901203) from 14 May 1996 to 21 June 1996.
65 % (at 24-hour reading) and 60 % (at 48-hour reading) of the animals of the test group were observed with positive skin reactions after treatment with a non-irritant test article concentration of 15 % in PEG 400.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: One animal of the test group (no. 353) was found dead on test day 23
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: One animal of the test group (no. 353) was found dead on test day 23
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
15 %
No. with + reactions:
13
Total no. in group:
20
Remarks on result:
other: ALPHA-HEXYLCINNAMALDEHYDE
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
15 %
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
Erythema
Remarks on result:
other: ALPHA-HEXYLCINNAMALDEHYDE

SKIN EFFECTS AFTER INTRADERMAL INDUCTION:


A normal development of the local symptoms was observed in the animals of the control and test group after the intradermal injections.


SKIN EFFECTS AFTER EPIDERMAL INDUCTION:


No erythematous or oedematous reaction was observed in the animals treated with polyethylene glycol 400 only. As the test article at 50% in polyethylene glycol 400 stained the skin orange, it was not possible to determine whether erythema was present or not. However, no oedema was observed.


SKIN EFFECTS AFTER THE CHALLENGE APPLICATION:


No positive reactions were observed in the animals neither when treated with polyethylene glycol 400 alone nor when treated with the test article at 50% in polyethylene glycol 400. An orange discoloration was noted directly after removal of the patch. To remove discoloration all animals were depilated approximately 3 hours prior to challenge reading.


 


MORTALITY / VIABILITY:


One animal of the test group (no. 353) was found dead on test day 23. In the lungs several dark red foci (D=3 mm) were noted. The death was considered to be treatment unrelated since no clinical signs or deaths were observed in any other animals.


 


CLINICAL SIGNS (SYSTEMIC):


No systemic symptoms were observed in the animals.


 


BODY WEIGHTS:


The body weight of the animals was within the range of physiological variability known for this strain and age.

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40557/A is not a considered as skin sensitizer in GPMT.
Executive summary:

In a GLP-compliant sensitivity study using the Maximization-Test, performed according to OECD guideline 406, guinea pigs were treated with the test substance. Twenty animals were treated with the test substance and ten animals with only the vehicle (polyethylene glycol 400). The concentrations of the test substance used in the main study were determined by the results of the preliminary study. The intradermal induction of sensitization in the test group was performed using 5 % of the test substance in both the vehicle and adjuvant/vehicle mixture. One week later this was boosted by the topical application of the test substance at 50 % concentration over the injection sites. Animals of the control group were treated in the same manner but only the selected vehicle was used. Two weeks after the second induction all animals were challenged by topical application of the test substance at 50 % concentration. No animals reacted positive after the challenge with 50 % of the test substance. One animal of the test group was found dead on test day 23, but the death was considered to be treatment unrelated since no clinical signs or deaths were observed in any other animal. Based on the study results, FAT 40557/A is not a considered as skin sensitizer in GPMT.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP-compliant sensitivity study using the Maximization-Test, performed according to OECD guideline 406, guinea pigs were treated with the test substance. Twenty animals were treated with the test substance and ten animals with only the vehicle (polyethylene glycol 400). The concentrations of the test substance used in the main study were determined by the results of the preliminary study. The intradermal induction of sensitization in the test group was performed using 5 % of the test substance in both the vehicle and adjuvant/vehicle mixture. One week later this was boosted by the topical application of the test substance at 50 % concentration over the injection sites. Animals of the control group were treated in the same manner but only the selected vehicle was used. Two weeks after the second induction all animals were challenged by topical application of the test substance at 50 % concentration. No animals reacted positive after the challenge with 50 % of the test substance. One animal of the test group was found dead on test day 23, but the death was considered to be treatment unrelated since no clinical signs or deaths were observed in any other animal. Based on the study results, FAT 40557/A is not a considered as skin sensitizer in GPMT.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the findings in the skin sensitisation study, the test substance does not need to be classified according EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.