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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:
From July 12, 2017 to July 20, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
The test substance is a complex UVCB with an undefined molecular weight and therefore the DPRA assay cannot be conducted. Therefore, an LLNA study – being the first choice animal method – was initiated. The pre-tests of this study demonstrated too high irritation up to dose levels of 1%. It is stated in the OECD 429 guideline that […Despite the advantages of the LLNA over TG 406, it should be recognised that there are certain limitations that may necessitate the use of TG 406 (13) (e.g. false negative findings in the LLNA with certain metals, false positive findings with certain skin irritants…]. Going any further down in dose levels to reach a non-irritant level is not any longer meaningful in view of risk assessment. Therefore, the GPMT (according to OECD Guideline 406) was selected as a more appropriate method for skin sensitization.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Based on the guinea pig maximisation test was conducted

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexamethylene diisocyanate, oligomers, reaction products with 3-methoxypropylamine
EC Number:
500-740-9
EC Name:
Hexamethylene diisocyanate, oligomers, reaction products with 3-methoxypropylamine
Cas Number:
162492-07-1
Molecular formula:
C38H69N9O9
IUPAC Name:
Hexamethylene diisocyanate, oligomers, reaction products with 3-methoxypropylamine
Specific details on test material used for the study:
CAS No.: 162492-07-1; Lot No.: 1591ZG-101; EINECS No.: 500-740-9; Purity: >98 %; Appearance: homogeneous, white powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
Dose level: 12%
Injection 1/ 0.1 mL FCA 1:1 with water
Injection 2/ 0.1 mL test item formulated in vehicle
Injection 3/ 0.1 mL test item formulated in a 1:1 mixture FCA/water
Day(s)/duration:
Day 0
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Dose level: 50%
The test item (in the minimal irritating concentration) was spread over 2 x 4 cm piece of gauze to saturation. The patch was secured with an occlusive dressing for 48 h.
Day(s)/duration:
Day 7
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
Dose level: 10%
The flanks of the treated and control animals were cleared of hair by shaving. Pieces of gauze saturated with the test item resp. vehicle were secured to the previously unexposed area of the animals for 24 h with the same type of occlusive bandage as for topical induction.
Day(s)/duration:
Days 21 and 22
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
4
Positive control substance(s):
no

Results and discussion

Positive control results:
Well defined erythema was seen 24 h after removal of the patches in 2/5 animals of the positive control group, and slight erythema for the remaining 3/5 animals. This result represents skin sensitization reaction in 100 % of tested animals. Slight erythema was still visible 48 h after removal of the patches in 3/5 animals. Oedema was not observed in any of the animals.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction / Intradermal Injection: 12 % Induction / Topical Application: 50 % Challenge / Topical Application: 10 %
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
Slight erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction / Intradermal Injection: 12 % Induction / Topical Application: 50 % Challenge / Topical Application: 10 %
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
Very slight erythema
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Not applicable
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No oedema or erythema was observed.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction / Intradermal Injection: 0.3%; Induction / Topical Application: 100%; Challenge / Topical Application: 100%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
Well defined erythema was observed in 2/5 animals 24 hours after removal of the patches. For the remaining 3/5 animals slight erythema was seen. This result represents skin sensitization reaction in 100 % tested animals.
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction / Intradermal Injection: 0.3%; Induction / Topical Application: 100%; Challenge / Topical Application: 100%
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
Slight erythema was still visible in 3/5 animals 48 hours after removal of the patches. No oedema was observed in animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not sensitizing.
Executive summary:

A study was conducted to determine the allergenic potential or sensitizing capacity of the test substance according to OECD 406 Guideline (guinea pig maximisation test), in compliance with GLP. Thirty-four guinea pig (Dunkin Hartley) females were used. The study was performed with 2 test groups: 1 negative control group (10 animals) and 1 treated group (20 animals). 4 additional animals were used in the pilot study to assess the irritation potency via intradermal and topical application, which was used to determine the test concentrations for induction and challenge phase. A parallel positive control group using α-Hexylcinnamaldehyde conducted on 5 animals was shared with a concurrent study and served as a reliability check. The animals were inspected daily during the study. All skin reactions and any unusual findings, including systemic reactions, results from induction and challenge procedures were observed and recorded. Individual weights of animals were determined shortly before the test substance was applied and at the end of the study. For the induction phase, the test substance was administrated in a concentration of 12 % for intradermal injection and 50 % for topical application. For the challenge phase, a concentration of 10 % was used. No clinical signs and no deaths in any of the groups were observed. The body weights of all animals increased during the study. No edema or erythema was observed in animals of control group (vehicle only). Slight erythema were observed in 5/20 animals of the treated group 24 hours after removal of the patches. This result represents skin sensitization reaction in 25 % of tested animals. Very slight erythema was observed in 3/20 animals 48 hours after removal of the patches. Oedema was not observed in any of the animals. Well defined erythema was seen 24 hours after removal of the patches in 2/5 animals of the positive control group, and slight erythema for the remaining 3/5 animals. This result represents skin sensitization reaction in 100 % of tested animals. Slight erythema was still visible 48 hours after removal of the patches in 3/5 animals. Oedema was not observed in any of the animals. Under the study conditions,according to the sensitization classification GHS and CLP the sensitization rate of the test substance is 25 %, thereforethe test substance is not sensitizing (Hozova, 2017).