sar- and analogue based safety assessments of cosmetic ingredients

1
Abstracts / Toxicology Letters 221S (2013) S59–S256 S229 P20-33 Risk assessment for hazardous substances contained in household product-cleaner and wet-tissue KunHo Park , Junghyun Park, Chan-Kook Kim, Jihye Shin, Jong-Hyeon Lee NeoEnBiz Co, Republic of Korea Recently, the exposure to hazardous substances contained in household products has a concern. In particular, cleaner and wet- tissue are one of the typical household products, which are used various chemicals. In this study, the exposure to 30 kinds of chem- icals, which are containable in cleaner and wet-tissue and can be exposed by dermal and inhalation pathway assessed according to tiered approach. Tiered approach is a logical stepwise process to risk assessment and uses the available information to the opti- mum extent while reducing unnecessary requirements for human exposure surveys or studies. Risk assessment of the present study was separated by tier 1 and tier 2. The tier 1, the worst case scenario was applied, was evaluated to screen target products and ingredients for tier 2, and ConsExpo model was applied. In the tier 2 assessment, the targeted products and ingredients were evaluated in detail, using measured data (migration, particle size distribution, etc.). The results of this study can be used to provide information about the management plan, according to the product type of cleaner and wet-tissue on the substances contained in the product safety standards of the target compounds. http://dx.doi.org/10.1016/j.toxlet.2013.05.552 P20-34 SAR- and analogue based safety assessments of cosmetic ingredients Thomas Petry , Daniela Jeronimo-Roque, Francesca Tencalla, Sanghamitra Mishra ToxMinds BVBA, B-1200 Brussels, Belgium The new EU Cosmetics Regulation (EC) 1223/2009 has replaced the former EU Cosmetics Directive 76/768/EEC and outlines the requirement for cosmetic product manufacturer to keep a prod- uct information file (PIF). An important aspect of the PIF is the availability of a detailed cosmetic safety report supporting the safe use of the cosmetic product and its ingredients. However, not for all ingredients present in today’s cosmetic products there will be sufficient ingredient-specific data to address each tox- icological endpoint individually and the animal testing ban for cosmetic product ingredients which came into force in March 2013 precludes the generation of new toxicology data in experimen- tal animals. Nevertheless, our current understanding of structure activity relationships paired with the high number of regulatory databases containing quality toxicology information allow the SAR- and analogue- or grouping based safety assessment of many cos- metic ingredients for most, if not all toxicological endpoints even in the absence of substance-specific toxicology data. This poster presentation will discuss on the basis of case studies structured approaches and frameworks how the safety of cosmetic ingredi- ents can be assessed on the basis of available toxicological data on structural analogues. This includes our strategies for identifi- cation of suitable analogues and chemical similarity assessment using IT tools (e.g., through determination of molecular similar- ity indices such as Tanimoto score), followed by assessment of the physico-chemical properties, structure reactivity and metabolism of the identified analogues and expert judgement on final chemical- specific assessment approach. http://dx.doi.org/10.1016/j.toxlet.2013.05.553 P20-35 The PCB effect database: A tool for translational research and health risk assessment Dennis Hellgren 1,, Jianyao Wu 1 , Robert Roos 1 , Emma Westerholm 1 , Oliver Adfeldt-Still 1 , Patrik Andersson 2 , Krister Halldin 1 , Helen Håkansson 1 1 Karolinska Institutet, Stockholm, Sweden, 2 Umeå University, Umeå, Sweden PCB exposure has been linked to adverse health outcomes, including developmental neurotoxicity, in human cohorts world- wide. Despite the wealth of published PCB data, there is a lack of knowledge to aid in the health risk assessment process. Data gaps are vast in several areas of developmental toxicity and the associ- ated mode-of-actions. The EU project ATHON addressed concerns raised by EFSA regarding the subgroup of PCB congeners, which is defined as non-dioxin-like (NDL). A toxicological effect database for these congeners was established and is under further development to aid in the health risk assessment. Initially, PubMed was searched for abstracts related to NDL-PCB congeners for the period between September 2005 to December 2012 and 769 references were identified. All of these were categorized based on toxicity type (i.e. neurotoxicity (22%); repro- ductive/developmental toxicity, or endocrine disruption (42%); liver toxicity and cancer (20%) and study type (in vitro (26%), in vivo (26%), or epidemiology (43%) study). Even though 769 abstracts were identified, only a small number could be entered into the effect database based on the inclusion criteria of individ- ual PCB compound studies with proven contamination of the test compound with dioxinlike impurities. A detailed analysis of the neurotoxicological section of the data base will be presented. Next, the PCB effect database will be used to accommodate data from mRNA arrays, e.g. as generated by the ATHON project using six NDL-PCB congeners with less than 0.00001% of dioxinlike impu- rities and thereby significantly increase and broaden its potential for translational research in the future. http://dx.doi.org/10.1016/j.toxlet.2013.05.554 P20-36 Toxicogenomics to group environmental chemicals in vitro? Alessa Ignarski 1,, Jessica Legradi 2 , Juliette Legler 2 , Helmut Segner 1 1 University of Bern, Bern, Schweiz, 2 VU University, Amsterdam, The Netherlands In our study we assessed the suitability of integrating tox- icogenomics into chemical classification. In order to make risk assessment of high numbers of chemicals feasible, chemicals have to be classified into groups, as thereby risk assessment can be done group-wise instead of substance by substance. One frequently used classification approach is to group chemicals according to their mode of action (MoA). However, a critical point in this grouping approach is the properties according to which substances can be

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Abstracts / Toxicology Letters 221S (2013) S59–S256 S229

P20-33Risk assessment for hazardous substancescontained in household product-cleaner andwet-tissue

KunHo Park ∗, Junghyun Park, Chan-Kook Kim, Jihye Shin,Jong-Hyeon Lee

NeoEnBiz Co, Republic of Korea

Recently, the exposure to hazardous substances contained inhousehold products has a concern. In particular, cleaner and wet-tissue are one of the typical household products, which are usedvarious chemicals. In this study, the exposure to 30 kinds of chem-icals, which are containable in cleaner and wet-tissue and can beexposed by dermal and inhalation pathway assessed according totiered approach. Tiered approach is a logical stepwise process torisk assessment and uses the available information to the opti-mum extent while reducing unnecessary requirements for humanexposure surveys or studies.

Risk assessment of the present study was separated by tier 1and tier 2. The tier 1, the worst case scenario was applied, wasevaluated to screen target products and ingredients for tier 2, andConsExpo model was applied. In the tier 2 assessment, the targetedproducts and ingredients were evaluated in detail, using measureddata (migration, particle size distribution, etc.).

The results of this study can be used to provide informationabout the management plan, according to the product type ofcleaner and wet-tissue on the substances contained in the productsafety standards of the target compounds.

http://dx.doi.org/10.1016/j.toxlet.2013.05.552

P20-34SAR- and analogue based safety assessments ofcosmetic ingredients

Thomas Petry ∗, Daniela Jeronimo-Roque, Francesca Tencalla,Sanghamitra Mishra

ToxMinds BVBA, B-1200 Brussels, Belgium

The new EU Cosmetics Regulation (EC) 1223/2009 has replacedthe former EU Cosmetics Directive 76/768/EEC and outlines therequirement for cosmetic product manufacturer to keep a prod-uct information file (PIF). An important aspect of the PIF is theavailability of a detailed cosmetic safety report supporting thesafe use of the cosmetic product and its ingredients. However,not for all ingredients present in today’s cosmetic products therewill be sufficient ingredient-specific data to address each tox-icological endpoint individually and the animal testing ban forcosmetic product ingredients which came into force in March 2013precludes the generation of new toxicology data in experimen-tal animals. Nevertheless, our current understanding of structureactivity relationships paired with the high number of regulatorydatabases containing quality toxicology information allow the SAR-and analogue- or grouping based safety assessment of many cos-metic ingredients for most, if not all toxicological endpoints evenin the absence of substance-specific toxicology data. This posterpresentation will discuss on the basis of case studies structuredapproaches and frameworks how the safety of cosmetic ingredi-ents can be assessed on the basis of available toxicological dataon structural analogues. This includes our strategies for identifi-cation of suitable analogues and chemical similarity assessmentusing IT tools (e.g., through determination of molecular similar-ity indices such as Tanimoto score), followed by assessment of the

physico-chemical properties, structure reactivity and metabolismof the identified analogues and expert judgement on final chemical-specific assessment approach.

http://dx.doi.org/10.1016/j.toxlet.2013.05.553

P20-35The PCB effect database: A tool for translationalresearch and health risk assessment

Dennis Hellgren 1,∗, Jianyao Wu 1, Robert Roos 1, EmmaWesterholm 1, Oliver Adfeldt-Still 1, Patrik Andersson 2, KristerHalldin 1, Helen Håkansson 1

1 Karolinska Institutet, Stockholm, Sweden, 2 Umeå University, Umeå,Sweden

PCB exposure has been linked to adverse health outcomes,including developmental neurotoxicity, in human cohorts world-wide. Despite the wealth of published PCB data, there is a lack ofknowledge to aid in the health risk assessment process. Data gapsare vast in several areas of developmental toxicity and the associ-ated mode-of-actions. The EU project ATHON addressed concernsraised by EFSA regarding the subgroup of PCB congeners, which isdefined as non-dioxin-like (NDL). A toxicological effect database forthese congeners was established and is under further developmentto aid in the health risk assessment.

Initially, PubMed was searched for abstracts related to NDL-PCBcongeners for the period between September 2005 to December2012 and 769 references were identified. All of these werecategorized based on toxicity type (i.e. neurotoxicity (22%); repro-ductive/developmental toxicity, or endocrine disruption (42%);liver toxicity and cancer (20%) and study type (in vitro (26%),in vivo (26%), or epidemiology (43%) study). Even though 769abstracts were identified, only a small number could be enteredinto the effect database based on the inclusion criteria of individ-ual PCB compound studies with proven contamination of the testcompound with dioxinlike impurities. A detailed analysis of theneurotoxicological section of the data base will be presented.

Next, the PCB effect database will be used to accommodate datafrom mRNA arrays, e.g. as generated by the ATHON project usingsix NDL-PCB congeners with less than 0.00001% of dioxinlike impu-rities and thereby significantly increase and broaden its potentialfor translational research in the future.

http://dx.doi.org/10.1016/j.toxlet.2013.05.554

P20-36Toxicogenomics to group environmentalchemicals in vitro?

Alessa Ignarski 1,∗, Jessica Legradi 2, Juliette Legler 2, HelmutSegner 1

1 University of Bern, Bern, Schweiz, 2 VU University, Amsterdam, TheNetherlands

In our study we assessed the suitability of integrating tox-icogenomics into chemical classification. In order to make riskassessment of high numbers of chemicals feasible, chemicals haveto be classified into groups, as thereby risk assessment can be donegroup-wise instead of substance by substance. One frequently usedclassification approach is to group chemicals according to theirmode of action (MoA). However, a critical point in this groupingapproach is the properties according to which substances can be