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Key value for chemical safety assessment

Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
clinical study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2011
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Prior to the start of the trials, the initial skin moisture of the test persons (female) was measured with the aid of a Corneometer® which detects the skins moisture retention in the superficial layers of the stratum corneum as deep as 10-20 μm (to be ensured that the measurement is not influenced bycapillary blood vessels). For two weeks, the human applied emulsions with different glycerin:ERYTHRITOL ratios (3:0; 2:1; 1:1; 1:2; 0:3) daily on their right forearm. Four measure points per test person were determined: one measure point where the skin has not been treated with the emulsion and three measure points where the skin has been treated with the emulsion. The main purpose of this study is to determine the ability of the substance to hydrate human skin,
as part of a cosmetic test. The authors of the study the authors of the study also evaluate the skin irritation potential of the substance. Given the animal model used (human) and the duration of the test (2 weeks), it can be considered reliable in assessing the potential for irritation of the skin by erythritol
GLP compliance:
not specified
Remarks:
Clinical test performed for cosmetic regulation n°1223/2009 compliance (efficacy claim support) relevant for REACH compliance
Type of study:
open epicutaneous test
Justification for non-LLNA method:
LLNA assay not avaialble, but clinical data used in a weight of evidence approach with sensitization data
Test material information:
Composition 1
Specific details on test material used for the study:
different glycerin:Erythritol ratios (3:0; 2:1; 1:1; 1:2; 0:3) then between 25% and 75%
Species:
other: human
Sex:
female
Details on test animals and environmental conditions:
healthy female test persons of different age and different skin type
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: glycerin
Concentration / amount:
25 to 75%
Day(s)/duration:
daily for 2 weeks
Adequacy of challenge:
other: up to 75% (non irritating substance)
No. of animals per dose:
10 persons per glycerin:Erythritol ratios (3:0; 2:1; 1:1; 1:2; 0:3)
Details on study design:
For statistical reasons four measure points per test person were determined: one measure point where the skin has not been treated with the emulsion and three measure points where the skin has been treated with the emulsion.
Challenge controls:
see above
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
test group
Dose level:
25 to 75%
No. with + reactions:
0
Total no. in group:
80
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Group:
negative control
Remarks on result:
not measured/tested
Remarks:
clinical test on volunteers to support substance safety and efficacy: no negative/control group
Group:
positive control
Remarks on result:
not measured/tested
Remarks:
clinical test on volunteers to support substance safety and efficacy: no negative/control group
Interpretation of results:
GHS criteria not met
Conclusions:
People who are sensitive or allergic to certain chemical components can have skin irritation, rashes or other allergic reactions when getting in contact with certain substances. None of the 80 test persons having erythritol (at 25% and up to 75%) on their skin reported any side effect, even those with dry or sensitive skin had no skin irritations during or after the testing period.
Executive summary:

In a clinical open test in 80 volunteers, application onto forearm of women. People who are sensitive or allergic to certain chemical components can have skin irritation, rashes or other allergic reactions when getting in contact with certain substances. None of the 80 test persons having erythritol (at 25% and up to 75%) on their skin reported any side effect, even those with dry or sensitive skin had no skin irritations during or after the testing period.

Endpoint:
skin sensitisation, other
Remarks:
skin puncture test and intradermal (ID) titration skin test
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2001
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reference:
Composition 0
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Case reports and clinical study on 2 Japanese volunteers who had experienced multiple reactions to erythritol containing foods: specific IgE antibody assay
GLP compliance:
not specified
Remarks:
available publication which does not precise GLP compliance status, nevertheless judged as relevant for REACH compliance
Type of study:
intracutaneous test
Justification for non-LLNA method:
skin puncture eventually followed by oral administration (challenge)
Test material information:
Composition 1
Species:
other: human volunteer
Sex:
male/female
Details on test animals and environmental conditions:
A 28-year-old woman developed generalized urticaria after eating various ERT-containing foods.
A 50-year-old man experienced 3 episodes of generalized urticaria, 2 of which included physician-documented hypotension (systolic BP readings, 90 and 74) after eating ERT-containing foods.
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
test group
Dose level:
100 mg/mL puncture skin test with more than 40 lots of erythritol (100 mg/mL in 50% glycerine)
No. with + reactions:
1
Total no. in group:
1
Clinical observations:
small amounts of histamine were released in a dose-dependent manner with both synthetic ERT (maximum release, 17%) and fermentation-derived ERT (maximum release, 23%).
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
0
Group:
test group
Dose level:
100 mg/mL intradermal titration skin test with erythritol solutions in saline solution between 4 and 20 mg/mL
No. with + reactions:
1
Total no. in group:
1
Clinical observations:
This first volunteer’s peripheral blood leukocytes released <8% total histamine when challenged in vitro with serial dilutions of erythritol
Remarks on result:
positive indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
1
Group:
test group
Dose level:
cumulative dose, 1.6 g by oral route
No. with + reactions:
1
Total no. in group:
1
Clinical observations:
facial swelling and urticaria
Remarks on result:
not determinable because of methodological limitations
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
test group
Dose level:
puncture skin tests with more than 40 lots of erythritol (100 mg/mL in 50% glycerine)
No. with + reactions:
0
Total no. in group:
1
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
negative control
Dose level:
100 mg/mL punture skin test - 7 healthy control subjects, 2 groups
No. with + reactions:
14
Total no. in group:
14
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
study cannot be used for classification
Conclusions:
anecdotal and unconfirmed reports of adverse reactions to ERT-containing products (estimated prevalence, <1 per million people) have appeared. Collectively, these data suggest that ERT might function as an allergen or hapten to mediate IgE-dependent anaphylactic reactions. Alternatively,a non–IgE-mediated mechanism of tissue mast cell or blood leukocyte activation might be operative. The pathophysiologic mechanisms underlying these reactions remain obscure.
Executive summary:

In a clinical study in 2 case reported of oral allergy to erythritol persons, contracdictory results on skin sensitization in skin puncture test and intradermal (ID) titration skin test.

Anecdotal and unconfirmed reports of adverse reactions to erythritol-containing products (estimated prevalence, <1 per million people) have appeared. Collectively, these data suggest that ERT might function as an allergen or hapten to mediate IgE-dependent anaphylactic reactions. Alternatively,a non–IgE-mediated mechanism of tissue mast cell or blood leukocyte activation might be operative. The pathophysiologic mechanisms underlying these reactions remain obscure for the publication authors.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Regarding low probability of:

- exposure by inhalation (boi:ling point 330°C, vapour pressure 33,6 mPa, particule size D50 = 550,5 µm)

- sensitization in humans (prevalence <1 per million people)

no significant respiratory sensitization potential is expected