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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vitro
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No guideline followed but test procedure scientifically validated.
Principles of method if other than guideline:
There are no official national or international guidelines for the DPRA Test; however, the study is performed according to the methods described in the following publications:
 Gerberick GF, Vassallo JD, Bailey RE, Chaney JG, Morrall SW, Lepoittevin JP. Development of a Peptide Reactivity Assay for Screening Contact Allergens. Toxicological Sciences 81,332-343, 2004.
 Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittenvin JP. Quantificationn of Chemical Peptide Reactivity for Screening Contact Allergens: A Classification Tree Model Approach. Toxicological Sciences 97(2), 417-427, 2007.
 Bauch C, Kolle SN, Fabian E, Pachel C, Ramirez T, Wiench B, Wruck CJ, van Ravenzwaay B, Landsiedel R. Intralaboratory validation of four in vitro assays for the prediction of the skin sensitizing potential of chemicals. Toxicology in Vitro 25, 1162 – 1168, 2011
GLP compliance:
yes (incl. QA statement)
Type of study:
other: Direct Peptide Reactivity Assay

The test substance was soluble in acetonitrile.

The mean C-peptide depletion, caused by the test substance was determined to be 58.3%.

The mean K-peptide depletion, caused by the test substance was determined to be 5.5%.

Thus, the mean peptide depletion was calculated to be 31.9%.

No co-elution of test substance and peptides was noticed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In vivo:

in an Guinea Pig Maximation Test according to OECD Guideline 406 (CIT 2003), the test substanc dissolved in 0.9% NaCl was assessed for its skin sensitizing with a concentration of 5%. Thirty guinea pigs were allocated to two groups: a control group of five males and five females and a treated group of ten males and ten females. with an oedema and/or crusts in 6/19 animals, was noted in 1/19, 5/19 and 12/19 animals, respectively. At the 48-hour reading, a moderate or intense erythema, together with an oedema,

dryness of the skin, crusts and/or a brownish area in 16/19 animals, was recorded in 5/19 and 13/19 animals, respectively.

Under the experimental conditions the test item HYDROXYETHYL IMIDAZOLIDONE METHACRYLATE (ureido methacrylate) induces delayed contact hypersensitivity in 18/19 (95%) guinea pigs and should therefore be considered as a sensitizer.

In vitro:

A combination of several in vitro methods addressing key steps of the adverse outcome pathway (AOP) for skin sensitization [1] as defined by OECD, has been conducted to assess the skin sensitizing potential of ureido methacrylate

 

·        protein reactivity(DPRA),

·        activation of keratinocytes(LuSens), and

·        activation of dendritic cells(MUSST).

 

 

The results of the individual studies are evaluated to predict the presence or absence of skin sensitizing potential of ureido methacrylate

 

The combination of test methods and the evaluation of their results has been evaluated and published by Bauch et al., 2012[2]. Based on the performance standards of the OECD test guideline no. 429 (Local Lymph Node Assay, LLNA, OECD 2010[3]), the evaluation based on the DPRA, LuSens and MUSST methods yields an overall accuracy of 95% compared to results in humans (for comparison: for the same data set the LLNA yielded an overall accuracy of 86%).

A skin sensitizing (quantitative) potency assessment using the reported results was not validated at the time of writing of this report.

Evaluation criteria for individual tests are:

Test method

Endpoint

Evaluation criteria

Direct Peptide Reactivity Assay (DPRA)

Peptide depletion

Positiveif ≥6.38% mean peptide depletion

Negativeif <6.38% mean peptide depletion

Keratinocyte Activation Assay - LuSens

ARE-dependent luciferase activity

Positiveif ≥1.5-fold luciferase activity when viability is >70% of the vehicle control

Negativeif <1.5-fold luciferase activity

Dendritic Cell Line Activation Assay

Myeloid U937 Skin Sensitization Test (MUSST)

CD86 expression

Positiveif ≥1.2-fold of CD86 when viability is >70% of the control

Negativeif <1.2-fold of CD86

Direct Peptide Reactivity Assay: Positive

31.9% mean peptide depletion

(58.3% cysteine peptide depletion; 5.5% Iysine peptide depletion)

 

Keratinocyte Activation Assay (LuSens): Positive

Inatleasttwo independent experiments a luciferase activity induction above 1.5-fold at test

substance concentrations that did not reduce cell viability below 70% was observed.

 

Dendritic Cell Line Activation Assay Myeloid U937 Skin Sensitization Test(MUSST): Positive

ln atleasttwoindependentexperiments an induction of the expression of CD 86 above 1.2-fold

was observed at sufficiently non-cytotoxic(cell viability 70%) concentration.

Based on the results of the in vitro tests applying the evaluation criteriaureido methacrylateis predicted to be a skin sensitizer.


[1]OECD 2012:The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins (2012) OECD ENVIRONMENT, HEALTH AND SAFETY PUBLICATIONS: No.168; ENV/JM/MONO(2012)10

http://search.oecd.org/officialdocuments/displaydocumentpdf/?cote=env/jm/mono(2012)10/part1&doclanguage=en last accessed 05 Feb 2013

[2]Bauch C Kolle SN, Ramirez T, Eltze T, Fabian E, Mehling A, Teubner W, van Ravenzwaay B, Landsiedel R., 2012.Putting the parts together: combining in vitro methods to test for skin sensitizing potentials. Regul Toxicol Pharmacol. 63: 489-504.

[3]OECD 2010: OECD GUIDELINE FOR THE TESTING OF CHEMICALS 429 Skin Sensitization: Local Lymph Node Assay (adopted July 2010)

http://www.oecd-ilibrary.org/docserver/download/9742901e.pdf?expires=1361285265&id=id&accname=guest&checksum=0F8779438DAD60D05DF9CD1DDABC2555



Migrated from Short description of key information:
In vivo Sensitziation Test:
Maximization Test (guinea pigs): sensitizing
In vitro Sensitization Test:
Direct Peptide Reactivity Assay (DPRA): Positive
Keratinocyte Activation Assay (LuSens): Positive
Dendritic Cell Line Activation Assay Myeloid U937 Skin Sensitization Test (MUSST): Positive

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information available on the potential for Ureidomethacrylate to produce respiratory sensitisation in animals or humans.


Migrated from Short description of key information:
No data available

Justification for classification or non-classification

Skin Sensitization:

Based on the available data of ureido methacrylate for skin sensitization, the substance has to be classified as skin sensitisation (Xn, R43 according to Directive 67/548/EEC (DSD) and skin sensitisation cat. 1B, H317 according to Regulation (EC) No 1272/2008 (CLP, GHS).

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