Hexahydro-4,7-methano-1H-indenyl acrylate

Endpoint summary

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP but not guideline compliant. There are no national or international guidelines for the DPRA Assay.

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 (DPRA)

The test substance was soluble in acetonitrile. However when mixed with the peptide stock solution the samples of the C-peptide became cloudy directly after preparation. After 24 hours precipitates were noticed in the samples of both peptides, additionally. Thus the samples of both peptides were centrifuged prior to HPLC analysis.

The mean C-peptide depletion, caused by the test substance was determined to be 100%.

The mean K-peptide depletion, caused by the test substance was determined to be 57.2%.

Thus, the mean peptide depletion was calculated to be 78.6%. Based on the observed results and applying the prediction model proposed in Gerberick et. al (2007) it was concluded that Dihydrodicyclopentadienylacrylate shows a high chemical reactivity in the DPRA under the test conditions chosen.

Interpretation of results:

other: shows a high chemical reactivity

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In vitro Sensitization Test Battery:

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 dihydrodicyclopentadienyl acrylate.

 

·        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 dihydrodicyclopentadienyl acrylate.

 

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

78.6% mean peptide depletion (100.0% cysteine peptide depletion; 57.2% Iysine peptide depletion)

 

Keratinocyte Activation Assay (LuSens): Positive

In at least two 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 at least two independent experiments 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 criteria dihydrodicyclopentadienyl acrylate 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

The OECD toolbox vs.2.1 predicted a Michael-type nucleophilic addition for the substance, i.e. a protein-binding potential. dihydrodicyclopentadienyl acrylate can be expected to be a potential skin sensitizer as are most of the acrylate esters.

Migrated from Short description of key information:
In vitro Sensitization Test:
Direct Peptide Reactivity Assay (DPRA): Positive
Kerationocyte Activation Assay (LuSens): Positive
Dendritic Cell Line Activation Assay Myeloid U937 Skin Sensitization Test (MUSST): Positive

Justification for selection of skin sensitisation endpoint:
The key study was selected

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There is no information available on the potential for Hexahydro-4,7-methano-1H-indenyl acrylate to produce respiratory sensitisation in animals or humans.

Migrated from Short description of key information:
No data available.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

Classification and labelling as a skin sensitizer (R43)

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008 (last amended by EC/286/2008 (2011-03-10)):

Classification and labelling as a skin sensitizer (category 1)