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Diss Factsheets

Administrative data

Description of key information

The test substance is not considered to be a skin sensitiser.

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:
12 September 2001 to 22 October 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC Ltd., 4452 Itingen, Switzerland
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:
Identification: FAT 40'800/B
Description: dark orange powder
Batch number: REM1'
Purity: approx. 70 %
Stability of test item: Stable under storage conditions;
Expiration date: 14-AUG-2007
Stability of test item dilution: Stable in bi-distilled water and in a 1:1 (v/v) mixture of FCA/physiological saline for at least 24 hours at room temperature.
Storage conditions: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.
Species:
guinea pig
Strain:
other: Ibm: GOHI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age at pretest start/beginning of acclimatization period: 4 - 6 weeks
- Body weight at pretest start: 376 - 391g
- Body weight at beginning of acclimatization period: Control and test group: 362-415 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Provimi Kliba 3418, batch no. 91/01, guinea pig breeding / maintenance diet, containing Vitamin C (Provimi Kliba AG, CH-4303 Kaiseraugst), ad libitum.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: One week for the control and test group under test conditions after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3 °C
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12, music during light period.
Route:
intradermal
Vehicle:
water
Remarks:
bi-distilled water
Concentration / amount:
10%; 0.1 ml/site
Day(s)/duration:
Day 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
bidistilled water
Concentration / amount:
50%; 0.3 g at a volume of approximately 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, open
Vehicle:
water
Concentration / amount:
50 %; 0.2 g
Day(s)/duration:
Day 22
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Intradermal pretest: 1, Epidermal pretest: 2, Control group: 5, Test group: 10.
Details on study design:
- Pretest intradermal injections: Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline were made into the shaved neck of one guinea pig (no. 173). One week later intradermal injections (0.1 mL/site) were made into the clipped flank of the same guinea pig at concentrations of 10, 5 %, and 3% of the test item in bidistilled water. The concentration of 10 % was considered to be the highest technically applicable concentration which could be injected into the intra-cellular space in spite of the obstacle caused by the tissues. Dermal reactions were assessed 24 hours later.
- Pretest epidermal applications: Four intradermal injections (0.1 mL/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline were made into the shaved neck of two 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 (3x3 cm) were saturated with the test item at 50 % (technically the highest possible concentration to be applied sufficiently), 25 %, 15 %, and 10 % in bi-distilled water and applied to the clipped and shaved flanks. The amount of test item preparation applied was approximately 0.2 g for the test item at 50 % and a volume of approximately 0.2 mL was applied for the remaining test item concentrations. 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 item. The dressings were removed after an exposure period of 24 hours. Twenty-one hours after removal of the dressing the application site was depilated with an approved depilatory cream (VEET Cream, Reckitt & Colman AG, CH-4123 Allschwil) in order to visualize any resulting erythema. 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. Thereafter, the animals were 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 according to the method of Magnusson and Kligman.

- Main test:
Induction: 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: Test Group: 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline, 2) The test item, at 10 % in bi-distilled water, 3) The test item at 10 % in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline. Control Group: 1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline, 2) Bi-distilled water, 3) 1:1 (w/w) mixture of bi-distilled water in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
- Main test: Induction: Epidermal applications:
On test day 7 and approximately 24 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 pretreated with 0.5 mL of 10 % Sodium-Lauryl-Sulfate (SLS) in paraffinum per liquidum as no primary irritation had been observed in the pretest. 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 item (50 % in bidistilled water) 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 plaster 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 bi-distilled water only, applied at a volume of approximately 0.3 mL. The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema according to the method of Magnusson and Kligman.
- Main test: Challenge:
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 (3x3 cm) of filter paper were saturated with the test item at the highest tested non-irritating concentration of 50 % (applied to the left flank) and the vehicle only (bi-distilled water 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. The reaction sites were assessed 24 and 48 hours after removal of the bandage for erythema and oedema according to the method of Magnusson and Kligman.
Challenge controls:
The control animals were treated in the same way as described above.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole
Positive control results:
All 10 test animals showed discrete/patchy to intense erythema and swelling at the 24- and 48-hour reading after the challenge treatment with 2-mercaptobenzothiazole at 0.5 % (w/w) in mineral oil.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
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:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
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:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: 2-mercaptobenzothiazole
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: 2-mercaptobenzothiazole

- Selection of concentrations of test item for main study: Intradermal Induction: The 10 % concentration of test item used for the intradermal induction exposure was well tolerated systemically and was the highest technically applicable concentration, Epidermal Induction: The 50 % concentration of test item used for the epidermal induction exposure was the highest attainable concentration which could be applied and was well-tolerated systemically. This concentration did not cause any skin irritation but was nevertheless selected because it was the highest attainable concentration, Epidermal Challenge: The 50 % concentration of the test item used for the challenge application was non-irritant and was the maximum concentration attainable.

RESULTS

- After intradermal induction: The expected and common findings were observed in the control and test group after the different applications using Freund's Complete Adjuvant intradermally. These findings consisted of erythema, oedema, necrotizing dermatitis, encrustation, exfoliation of encrustation and also red discoloration produced by the test item.

- After epidermal induction: Discrete/patchy erythema was observed in all animals at the 24-hour reading and in four out of 5 animals at the 48-hour reading after treatment with bi-distilled water only. As the test item at 50 % stained the skin red-brown, it was not possible to determine whether erythema was present or not. However, no oedema was observed.

- After the challenge: No skin reactions were observed in the animals when treated with either bi-distilled water only or when treated with the test item at 50 % in bi-distilled water in the control and test group. Red-brown discoloration produced by the test item was noted directly after removal of the patch.

- There were no deaths during the course of the study and no signs of systemic toxicity were observed in the animals. Two animals of the control group showed a loss of body weight (3.0 - 4.7 %) during the acclimatization period. One animal recovered between the treatment start and the end of the study whereas the other animal continued losing body weight (2.8 %) until the end of the study. The body weight of the other animals was within the range commonly recorded for animals of this strain and age.

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40800/A is not a sensitizer in GPMT assay.
Executive summary:

In a GLP-compliant sensitivity study using the Maximization-Test, performed according to OECD guideline 406, female albino guinea pigs were treated with the test substance. Ten animals were treated with test substance and five animals with only the vehicle. The intradermal induction of sensitization in the test group was performed in the nuchal region with a 10 % dilution of the test item in bi-distilled water and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 50 % in bi-distilled water one week after the intradermal induction and following pretreatment of the test areas with 10 % Sodium-Lauryl-Sulfate (SLS) approximately 24 hours prior to application of the test item. The animals of the control group were intradermally induced with bi-distilled water and FCA/physiological saline and epidermally induced with bi-distilled water under occlusion following pretreatment with 10 % SLS. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 50 % in bi-distilled water and bi-distilled water alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing. No toxic symptoms were evident in the guinea pigs of the control or test group and no deaths occurred. None of the control and test animals showed skin reactions after the challenge treatment with the test substance at 50 % (w/w) in bi-distilled water. Based on the study findings, the test substance is not considered to be a skin sensitizer.

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, female albino guinea pigs were treated with the test substance (RCC 2001). Ten animals were treated with test substance and five animals with only the vehicle. The intradermal induction of sensitization in the test group was performed in the nuchal region with a 10 % dilution of the test item in bi-distilled water and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the test item at 50 % in bi-distilled water one week after the intradermal induction and following pretreatment of the test areas with 10 % Sodium-Lauryl-Sulfate (SLS) approximately 24 hours prior to application of the test item. The animals of the control group were intradermally induced with bi-distilled water and FCA/physiological saline and epidermally induced with bi-distilled water under occlusion following pretreatment with 10 % SLS. Two weeks after epidermal induction the control and test animals were challenged by epidermal application of the test item at 50 % in bi-distilled water and bi-distilled water alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing. No toxic symptoms were evident in the guinea pigs of the control or test group and no deaths occurred. None of the control and test animals showed skin reactions after the challenge treatment with the test substance at 50 % (w/w) in bi-distilled water. Based on the above mentioned findings the test substance is not considered to be a skin sensitiser.

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 to the Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008