Decision Tool for Assessing Polymers and Polymeric ... SOT Poster.pdf · Decision Tool for...
1
Decision Tool for Assessing Polymers and Polymeric Substances Decision Tool for Assessing Polymers and Polymeric Substances with Potential Hazards to Human Health with Potential Hazards to Human Health 1 Bernard Gadagbui, 1 Andrew Maier, 1 Patricia Nance, 2 Michael Jayjock, 2 Claire Franklin; 1 Toxicology Excellence for Risk Assessment, 2 The LifeLine Group Overview of the Polymer Hazard Characterization Decision Framework Overview of the Polymer Hazard Characterization Decision Framework *See Detailed Hazard CharacterizaƟon Decision Tree for Polymers Abstract Abstract Polymers display a wide variety characterisƟcs – e.g., presence of non‐bound residual monomers, polymerizaƟon chemicals, degradaƟon products, and addiƟves – that can generate a potenƟal health hazard. There is a paucity of direct tesƟng data on many polymers to adequately evaluate their toxicity, but several regulatory agencies have provided guidance for as‐ sessing polymer safety. We evaluated each of these approaches and idenƟfied the strengths and weaknesses of each. No single published model appears to cover all characterisƟcs of interest and this suggests the need to develop a comprehen‐ sive decision tool to idenƟfy polymeric substances that may pose potenƟal toxicological hazards to human health. We de‐ veloped a decision tool that incorporates a weight of evidence approach integraƟng informaƟon for many individual hazard flags. Hazard flags were placed into four broad categories: (1) empirical hazard informaƟon on the polymer or residual monomer; (2) evidence of toxicity based on structural properƟes (i.e., based on polymer class, monomer components, or reacƟve funcƟonal groups); (3) potenƟal for significant Ɵssue dose (i.e., based on molecular weight distribuƟon or systemic bioavailability); and (4) hazard based on foreseeable special use consideraƟons. Some of these hazard flags have not been considered previously by the regulatory agencies. We tested this approach for a number of polymers to demonstrate how the tool integrates all available regulatory approaches and provides a comprehensive decision framework for evaluaƟng pol‐ ymer safety. Introduction Introduction Why is this framework needed? Several regulatory agencies have guidance on assessing polymer safety No single published model covers all characterisƟcs of interest Suggests the need to develop a comprehensive decision tool Approach Approach Intended to cover the assessment of polymers based on their innate propensity to cause toxic effects Also taking into consideraƟon the impacts of polymer uses and exposure scenario informaƟon that directly impacts the characterizaƟon of hazard potenƟal Designed with several guiding principles Provision for incorporaƟng weight of evidence principles in reaching the ul Ɵmate conclusion regarding hazard potenƟal Need to reflect the preference for direct hazard data over surrogate or indirect evidence of hazards, without providing too rigid a hierarchy Breadth of applicability to polymers with wide ranging characterisƟcs and data sets. for most applicaƟons, the assessments will be done with a paucity of direct hazard informaƟon a robust set of criteria to capture a range of physical or chemical characterisƟcs in the weight of evidence decision is provided. RecogniƟon that hazard potenƟal reflects innate properƟes, many of which reflect the ability to achieve an adequate Ɵs‐ sue dose ProperƟes related to toxicokineƟcs (e.g., bioavailability or release of toxic molecules) as well as toxicodynamics (presence of biologically acƟve reacƟve funcƟonal groups) are included in the assessment Hazard potenƟal may also reflect directly special use condiƟons or exposure scenarios – and such consideraƟons are in‐ cluded in the process Hazard Evaluation Form Hazard Evaluation Form Documents the presence or absence of important hazard flags relevant to the polymer under review Lists flags under one of four quesƟon categories Presence of a hazard flag is based on the specific criteria for each parameter Presence of any one flag triggers a check for the overall hazard flag within a quesƟon category A check in any one quesƟon is translated to a “yes” answer in the Final Hazard CharacterizaƟon Decision Flow Chart for that quesƟon All “yes” quesƟons then must be evaluated, using professional judgment, to determine whether the var‐ ious flags consƟtute a moderate or high concern based on the science If no hazard flags are checked, this result is translated as a “no” answer in the Final Hazard Characteriza‐ Ɵon Decision Flow Chart for that quesƟon Four Question Categories Four Question Categories Q.1. Is there sufficient empirical evidence of toxicity? Q.2. Is there sufficient evidence of toxicity based on structural properƟes (i.e., based on polymer class, monomer components, or reacƟve funcƟonal groups)? Q.3. Is there potenƟal for significant Ɵssue dose (i.e., based on molecular weight distribuƟon, reacƟve funcƟonal groups, charge density, or systemic bioavailability)? Q.4. Is there addiƟonal hazard based on foreseeable special use consideraƟons? Weight of Evidence Decision Flow Chart Weight of Evidence Decision Flow Chart Detailed Hazard Characterization Decision Tree for Polymers Detailed Hazard Characterization Decision Tree for Polymers Chemical Class Empirical Hazard Information Monomer Components Molecular Weight Distribution Relative Functional Group/Side Chain Conclusion Conclusion We have developed a framework for assessing polymers and polymeric substances with potenƟal for haz‐ ards to human health Final determinaƟon of hazard potenƟal reflects a weight of evidence decision that integrates infor‐ maƟon for many individual hazard flags Order of data to flag a polymer: relevant and reliable empirical toxicity data > toxicity based on struc‐ tural properƟes > potenƟal for significant Ɵssue dose > foreseeable use consideraƟons Re‐evaluate polymer if new data becomes available. Funding for this project was provided by Health Canada under the standing offer contract #4600000343. Guidance Documents Reviewed Guidance Documents Reviewed United States Europe Canada Australia Japan Korea China A complete list of references available on request. A literature search was conducted to supplement above list of agency documents.
Transcript of Decision Tool for Assessing Polymers and Polymeric ... SOT Poster.pdf · Decision Tool for...
DecisionToolforAssessingPolymersandPolymericSubstancesDecisionToolforAssessingPolymersandPolymericSubstanceswithPotentialHazardstoHumanHealthwithPotentialHazardstoHumanHealth
1Bernard Gadagbui, 1Andrew Maier, 1Patricia Nance, 2Michael Jayjock, 2Claire Franklin; 1Toxicology Excellence for Risk Assessment, 2The LifeLine Group
OverviewofthePolymerHazardCharacterizationDecisionFrameworkOverviewofthePolymerHazardCharacterizationDecisionFramework
*See Detailed Hazard Characteriza on Decision Tree for Polymers
AbstractAbstract Polymers display a wide variety characteris cs – e.g., presence of non‐bound residual monomers, polymeriza on chemicals, degrada on products, and addi ves – that can generate a poten al health hazard. There is a paucity of direct tes ng data on many polymers to adequately evaluate their toxicity, but several regulatory agencies have provided guidance for as‐sessing polymer safety. We evaluated each of these approaches and iden fied the strengths and weaknesses of each. No single published model appears to cover all characteris cs of interest and this suggests the need to develop a comprehen‐sive decision tool to iden fy polymeric substances that may pose poten al toxicological hazards to human health. We de‐veloped a decision tool that incorporates a weight of evidence approach integra ng informa on for many individual hazard flags. Hazard flags were placed into four broad categories: (1) empirical hazard informa on on the polymer or residual monomer; (2) evidence of toxicity based on structural proper es (i.e., based on polymer class, monomer components, or reac ve func onal groups); (3) poten al for significant ssue dose (i.e., based on molecular weight distribu on or systemic bioavailability); and (4) hazard based on foreseeable special use considera ons. Some of these hazard flags have not been considered previously by the regulatory agencies. We tested this approach for a number of polymers to demonstrate how the tool integrates all available regulatory approaches and provides a comprehensive decision framework for evalua ng pol‐ymer safety.
IntroductionIntroduction Why is this framework needed?
Several regulatory agencies have guidance on assessing polymer safety
No single published model covers all characteris cs of interest
Suggests the need to develop a comprehensive decision tool
ApproachApproach Intended to cover the assessment of polymers based on their innate propensity to cause toxic effects
Also taking into considera on the impacts of polymer uses and exposure scenario informa on that directly impacts the
characteriza on of hazard poten al
Designed with several guiding principles
Provision for incorpora ng weight of evidence principles in reaching the ul mate conclusion regarding hazard poten al
Need to reflect the preference for direct hazard data over surrogate or indirect evidence of hazards, without providing too rigid a hierarchy
Breadth of applicability to polymers with wide ranging characteris cs and data sets. for most applica ons, the assessments will be done with a paucity of direct hazard informa on a robust set of criteria to capture a range of physical or chemical characteris cs in the weight of evidence decision is
provided.
Recogni on that hazard poten al reflects innate proper es, many of which reflect the ability to achieve an adequate s‐sue dose
Proper es related to toxicokine cs (e.g., bioavailability or release of toxic molecules) as well as toxicodynamics (presence of biologically ac ve reac ve func onal groups) are included in the assessment
Hazard poten al may also reflect directly special use condi ons or exposure scenarios – and such considera ons are in‐cluded in the process
HazardEvaluationFormHazardEvaluationForm
Documents the presence or absence of important hazard flags relevant to the polymer under review
Lists flags under one of four ques on categories
Presence of a hazard flag is based on the specific criteria for each parameter
Presence of any one flag triggers a check for the overall hazard flag within a ques on category
A check in any one ques on is translated to a “yes” answer in the Final Hazard Characteriza on Decision Flow Chart for that ques on
All “yes” ques ons then must be evaluated, using professional judgment, to determine whether the var‐ious flags cons tute a moderate or high concern based on the science
If no hazard flags are checked, this result is translated as a “no” answer in the Final Hazard Characteriza‐on Decision Flow Chart for that ques on
FourQuestionCategoriesFourQuestionCategories Q.1. Is there sufficient empirical evidence of toxicity? Q.2. Is there sufficient evidence of toxicity based on structural proper es (i.e., based on polymer class, monomer components, or reac ve func onal groups)? Q.3. Is there poten al for significant ssue dose (i.e., based on molecular weight distribu on, reac ve func onal groups, charge density, or systemic bioavailability)? Q.4. Is there addi onal hazard based on foreseeable special use considera ons?
WeightofEvidenceDecisionFlowChartWeightofEvidenceDecisionFlowChart
DetailedHazardCharacterizationDecisionTreeforPolymersDetailedHazardCharacterizationDecisionTreeforPolymers
ChemicalClass
EmpiricalHazardInformation
MonomerComponents
MolecularWeightDistribution
RelativeFunctionalGroup/SideChain
ConclusionConclusion
We have developed a framework for assessing polymers and polymeric substances with poten al for haz‐
ards to human health
Final determina on of hazard poten al reflects a weight of evidence decision that integrates infor‐
ma on for many individual hazard flags
Order of data to flag a polymer: relevant and reliable empirical toxicity data > toxicity based on struc‐
tural proper es > poten al for significant ssue dose > foreseeable use considera ons
Re‐evaluate polymer if new data becomes available.
FundingforthisprojectwasprovidedbyHealthCanadaunderthestandingoffercontract#4600000343.
GuidanceDocumentsReviewedGuidanceDocumentsReviewed United States
Europe
Canada
Australia
Japan
Korea
China A complete list of references available on request. A literature search was conducted to supplement above list of agency documents.
![Designing polymeric microparticles for biomedical and ... · of natural polymers [29]. In addition, natural polymers also offer ease of processing [30] and of chemical modification](https://static.fdocuments.net/doc/165x107/5f0950737e708231d4263d25/designing-polymeric-microparticles-for-biomedical-and-of-natural-polymers-29.jpg)
