Arnot, J.A.

Bennett, D.H.

Csiszar, S.A.

Ernstoff, Alexi

Fantke, Peter

Jolliet, O.

Shin, H.

Wetmore, B.A.

Online Research Database In Technology

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Downloaded from orbit.dtu.dk on: Dec 20, 2017Flagging health risks of chemicals by combining in vitro bioactivity data withenvironmental and consumer product exposure modelingErnstoff, Alexi; Shin, H. ; Bennett, D.H. ; Arnot, J.A. ; Csiszar, S.A. ; Fantke, Peter; Wetmore, B.A. ;Jolliet, O.Published in:Abstract book - SETAC Europe 24th Annual MeetingPublication date:2014Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Ernstoff, A., Shin, H., Bennett, D. H., Arnot, J. A., Csiszar, S. A., Fantke, P., ... Jolliet, O. (2014). Flagging healthrisks of chemicals by combining in vitro bioactivity data with environmental and consumer product exposuremodeling. In Abstract book - SETAC Europe 24th Annual Meeting (pp. 45). SETAC Europe.testing physiological parameter here is BL intensity. The BL assaysystems are based on biological objects of different levels oforganization – bacteria-based or enzyme-based bioassays, providing for astudy of the effects of toxic compounds on cells or enzymes,respectively. Basing on a broad investigation of effects of model toxicexogenous compounds on BL assay systems, classification of the effectson the BL enzyme reaction was suggested. The effects were classified asphysical, chemical and/or biochemical ones. Five mechanisms arediscussed: (1) change in electron-excited states’ population and energytransfer, (2) change in the efficiency of the S-T conversion in thepresence of an external heavy atom, (3) change of rates of coupledreactions, (4) interactions with enzymes and variation of the enzymaticactivity, (5) nonspecific effects of electron acceptors. The broadexperience in investigation of effects of exogenous compounds makesthe BL assay systems to be a very convenient tool for studying toxicitymechanisms. The BL assays were found to be sensitive to alpha- andbeta-radionuclides. The role of peroxides and electron transfer inhormesis and toxic effects of radionuclides was studied. Changes inprotein secondary structure in bacterial cells exposed to radionuclideswas discussed in terms of a stress response of the bacterial cells to thelow-dose chronic radioactivity. The mutagenic effect of tritium wasstudied using restriction analysis of marker amplicons. Detoxification ofsolutions of metallic salts and organic oxidizers by humic substances(HS), products of natural transformation of organic matter in soils andbottom sediments, was studied. Detoxification mechanisms wererevealed to be complex, with chemical, biochemical, and cellular aspectsconditioning those. The detoxifying effects were explained by: (i)decrease of free toxic compound’ content in water solutions underbinding and redox neutralization by HS, (ii) increase of rates ofbiochemical processes in the bioassay system under HS influence, (iii)enhancement of mucous layers on cell surface as a cellular response tounfavorable impact of toxicants. Mechanisms (ii) and (iii) revealed anactive role of the bioassay systems in the detoxification processes.165 Flagging health risks of chemicals by combining in vitrobioactivity data with environmental and consumer productexposure modeling     A.S. Ernstoff, Quantitative SustainabilityAssessment; H. Shin, University of California  Davis; D.H. Bennett,Public Health Sciences; J.A. Arnot, ARC Arnot Research  Consulting /Department of Physical  Environmental Science; S.A. Csiszar,University of Toronto / Dept of Chemical Engineering and AppliedChemistry; P. Fantke, Technical University of Denmark / IER; B.A.Wetmore, The Hamner Institutes for Health Sciences / Institute forChemical Safety Sciences; O. Jolliet, University of Michigan / School ofPublic Health.  Combining in vitro bioactivity data with exposuremodels is essential to predict potential public health risks. We present atier 1 framework to flag chemical exposures of potential risk based on invitro bioactivity data for 229 chemicals from the US EPA. Tounderstand chemical-specific exposure, we refined thousands ofchemical categories in the US EPA ACToR/CpCat product database toharmonize with exposure modeling. Most chemicals matched several ofthe following exposure categories: direct intakes (e.g. food), dermalapplication (e.g. cosmetics), pesticides (e.g. ingestion of residues), andindoor and environmental emissions. Results were also cross-checkedwith the Household Product Database and FDA-approved foodadditives. We independently estimated population-scale chemical intakefractions due to environmental and indoor emissions and product intakefractions using three multi-media models (USEtox, CalTox, RAIDAR).Model results predicted similar trends within two orders of magnitudefor most chemicals. Intake fractions were multiplied by emissionestimates or production volumes to extrapolate daily intake of chemicalper unit bodyweight (mg/kg/day). Modeled intake doses per categoryvaried greatly across chemicals due to physicochemical properties andemission estimates - the main source of uncertainty. We found usingconservative approaches, that chemical intake due to consumer productuse generally exceeds intakes due to environmental exposures, with thegreatest intake being 2,600mg/kg/day for phenol in a personal careproduct. Population-scale average intake doses due to environmentalexposures were always less than 0.34 (mg/kg/day). When comparingintake estimates with the bioactivity data, we found 66 chemicals with amaximum intake that exceeds the minimum oral dose equivalents forobserved biological activity. For these 66 chemicals there were severalchemical/exposure classification combination that exceeded min oraldose equivalents: 12 cases due to environmental exposure, 20 cases dueto product use within home, 41 cases due to personal care product, and47 cases due to food ingestion. These chemical exposures are flagged asneeding to be further evaluated in order to understand possible publichealth threats.166 Second tier options in the EFSA Guidance Document on RiskAssessment of Plant protection products on bees (Apis mellifera,Bombus spp. and solitary bees)     C. Szentes, EFSA; F. Streissl, EFSA/ Pesticide Unit; D. Auteri, Auteri; R. Sharp, EFSA  European FoodSafety Authority.  Pesticides are considered as one factor among othersthat are contributing to the decline of pollinators. Moreover, the currentrisk assessment schemes for pesticides are not considered to be able toaddress the risk to pollinators in a comprehensive way. This indicatedthe need to review the current risk assessment schemes and to developnew, more sophisticated ones. As a response to this regulatorychallenge, the European Commission tasked EFSA to develop guidancefor pesticide risk assessment for bees. The new guidance document wasissued on July, 2013, but has not yet been adopted for use in regulatoryrisk assessments. The guidance document suggests the implementationof a tiered risk assessment scheme with a simple and cost-effective firsttier moving to more complex higher tiers (e.g. using field studies). Eachtier of the risk assessment ensures that the appropriate level of protectionis achieved. However, the guidance document was heavily criticised bydifferent stakeholders including the industry and some Europeanregulatory bodies. One of the main concerns raised by the industry wasthe severity of the first tier together with the unfeasibility of the highesttier options. However, there has been very little discussion regarding the2nd tier options, which is between the 1st tier and highest tier level. Anumber of 2nd tier options are suggested by the guidance documentwhich can be used to refine the estimation of the exposure of pollinatorsto pesticides when foraging on the treated plants. These options can alsobe used to provide a more realistic oral exposure estimate for larvae.Crop or compound specific data are needed at this tier, with which a lowrisk may be achieved. Consequently, there will be no need to performthe more complex and expensive field studies. As an example, it isexpected that using compound specific information on residue levels inpollen and nectar will provide a solution in many cases. For other casesdata on the sugar content of the nectar will be sufficient. Thepresentation will deliver an overview of the most important 2nd tieroptions that are included in the guidance document. Also, a case studywill be presented explaining how some of these options can be appliedin practice. 167 Development of a Toxicokinetic-Model of the Bee Hive.     K.Szonn, RWTH Aachen University / Institute for EnvironmentalResearch; C.D. Maus; H. Ratte, Research Institute for EcosystemAnalysis and Assessment – gaiac; M. Ross-Nickoll, RWTH Aachen /Institute for Environmental Research; W. Schmitt, Bayer CropScienceAG / Environmental Modelling; T.G. Preuss, Bayer CropScience /Institute for Environmental Research.  Pollination is an important factorof the food economy and the honey bee Apis mellifera is the mostimportant commercial pollinator. Over the last few years, potentialeffects of insecticides on bee colonies have been discussed. There islargely consensus that the risk assessment for bees will benefit from adeeper understanding of mechanisms of bee exposure to pesticides. Tounderstand the effects of toxicants in the bee hive it is important to fullyunderstand their fate within bee colonies. Literature data were analysedto determine the relevant toxicokinetic processes in the bee colony andhow these processes influence the fate of chemical substances in the beehive. To realistically estimate the quantity of chemical substances beesare exposed to within the hive, the whole process of resource collectionand processing has to be taken into account. We assume bee-to-bee-contact as the most important factor for the distribution of chemicalsubstances in the hive; physicochemical properties of the materials in45SETAC Europe 24th Annual Meeting

Flagging health risks of chemicals by combining in vitro bioactivity data with environmental and consumer product exposure modeling

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Flagging health risks of chemicals by combining in vitro bioactivity data with environmental and consumer product exposure modeling

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