Document ID: EPA-HQ-OPPT-2019-0499-0036
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2020-03-05T05:00Z

EPA SCIENTIFIC ADVISORY COMMITTEE ON CHEMICALS
                                   Issues Discussed to Date

 Introductory Text:

    ____ Discussion as to why this chemical has been included under TSCA is missing.
    ____ A summary of findings and decisions made as part of the Scoping and Problem Formulation steps is missing.
    ____ A summary of the current status of the target chemical under regulatory statutes is not provided (relevant regulatory statutes is listed, not status).
    ____ Gaps in regulation of the chemical of concern are not discussed (e.g. adjuvants in pesticides not regulated under FIFRA and not otherwise regulated).
    ____ Information provided insufficient to assess the completeness of the conceptual model used.
    ____ Conceptual model does not illustrate where ALL of the chemical that is manufactured and/or imported is used and/or disposed of (the mass-balance concept).
    ____ The scientific basis for policy decisions, such as the decision to not address exposures and hazards to the general population, are inadequately described.
            ____ The evaluation does not state clearly that the only environmental releases covered under the TSCA review are those exposures not covered under other regulations (what regulations cover what exposures are not provided).

 Systematic Review:

            ____ Systematic review process not reviewed by outside experts.
            ____ Systematic review protocol/rules inconsistently applied.
            ____ Systematic review is not transparent and objective.
            ____ Systematic review scoring system unclear.
            ____ Scientific literature review missing important papers.
            ____ Metrics used are overly stringent and exclude too many studies.
            ____ Gray literature is defined to simplistically and may not be fully explored and/or results fully utilized.
            ____ Gray literature results incorrectly labeled as peer-reviewed research findings.
            ____ Terms used in the quality review (like "unacceptable") are not well defined.
            ____ Unclear when results from low-quality studies can and cannot be used.
            ____ Quality review criteria for human studies not provided in the SR protocol.
            ____ Quality review of sources of physical-chemical property estimates not performed.
            ____ Secondary sources (like previous evaluation, review articles) used instead of going back to the primary literature for key data or findings.
            ____ Evaluation relies on sources of information that did not go through a quality review and/or were scored using a different system.
            ____ Industry data sources are not held to the same quality standards as published research.

 Physical-Chemical properties:

            ____ Physical-chemical property data are limited or non-existent.
            ____ Estimates are not provided for all important physical-chemical properties (e.g. no blood: air partition coefficient for 1,4 Dioxane).
            ____ Source of physical-chemical property data not provided.
            ____ Source of physical-chemical property data of low or unknown quality.
            ____ Variability or uncertainty of physical-chemical property estimates not discussed.
            ____ When multiple estimates are available for a physical-chemical property, no justification is provided for the specific estimate used in the evaluation.
            ____ Text uses vague and/or inaccurate language in discussing physical-chemical properties.

 Environmental Fate:

            ____ Little or no monitoring data and incomplete accounting of inputs (production and imports), uses, products, and disposal result in gross underestimates of expected environmental releases.
            ____ Available information does not account for all environmental discharges and the predicted amounts underestimate releases (needs a mass-balance or production-to -disposal balance).
            ____ Not all releases (to air, water, and soils) are assessed.
            ____ Surface runoff and other non-point source releases to water not assessed.
            ____ Evaluation is inconsistent in how major fate processes are discussed  -  dismissed in one section, discussed in another.
            ____ There is uncertainty in how and which available data were used with models to estimate fate.
            ____ Model used to support estimation of releases to air, soil, water or sediment require assumptions not met by the chemical or associated processes under evaluation. 
            ____ Sensitivity of models to key inputs not assessed.
            ____ Assertions of the persistence of the chemical in the environment do not include the underlying rationale.
            ____ Mechanisms for movement from land applications to groundwater and hence to surface waters not discussed.
            ____ Releases from major spills or fires not acknowledged and/or discussed.
            ____ Uptake by terrestrial plants and potential for trophic transfer to animals not discussed.
            ____ Major metabolites of the target chemical not included when estimating potential exposures.
            ____ Discharges relative to stream flow not discussed or utilized when determining the impact of releases.
            ____ Discharges from multiple sources to the same stream or in close proximity to each other not considered as one large release.

 Environmental Exposures and choice of Target Receptors:

            ____ Some pathways are excluded (e.g. no terrestrial pathways, or no aquatic pathways, etc) with weak or no justification. 
            ____ Rationale for excluding certain receptors of environmental exposures (e.g. sediment dwelling organisms, fish feeding birds, etc) weak or not provided.
            ____ The rationale and reliability for the model/estimation method used to measure exposures is not provided.
            ____ Inability to properly characterize exposures to certain receptors due to lack of data and/or inadequacy of available models not acknowledged or accounted for in uncertainty assessment. 
            ____ Impact of chemical releases on environmental processes (e.g. ozone depletion, global warming) that ultimately impact human and non-human receptors is not discussed.
            ____ Extent of exposures to threatened and endangered species (e.g. honeybees) not discussed or included in assessment.
            ____ The dearth of actual data precludes having a robust assessment of environmental exposures.

 Environmental Hazard, Risk Scenarios, and Risk Characterization:
       
    ____ Targets used do not fully represent species potentially exposed (e.g. land waste disposal but no assessment of terrestrial receptors). 
    ____ Impacts on threatened and endangered species not discussed.
    ____ Assessment of potential exposures to important targets (e.g. terrestrial vertebrates, amphibians, etc.) is missing or other inadequate. 
    ____ Conclusion of insignificant exposure to select targets not well justified.
    ____ Dose-response analysis inadequate or improperly interpreted.
    ____ Adjustment factors (AFs) applied do not fully account for uncertainty.
    ____ Point of departure chosen in the evaluation not well justified or poorly explained.
    ____ Confidence bounds on E-FAST predictions able to be calculated but not provided.
    ____ Claims of the potential for bioaccumulation not justified and/or contradicted by available data.
    ____ Adjustment factors used in the calculation of the Concentration of Concern is too small to account for limits/uncertainties on available data.

 Occupational Users' Exposure:

    ____ Some scenarios are not well-defined, missing some of the determining factors (e.g. estimated values for room size, general ventilation, etc...).
    ____ Number of workers exposed underestimated by limiting facilities discussion to only those represented in the TRI reports (use in addition the NPDES).
    ____ Key scenarios related to occupational users' exposures not discussed (e.g. agricultural workers exposed to chemical as adjuvant in pesticide formulation).
    ____ Assumptions made in estimating occupational exposures (be it inhalation or dermal or both) for some or all scenarios are not stated, inadequately described, or not supported by available information/evidence.
    ____ Model used to estimate exposure (near-field, far-field, etc.) for certain scenarios are not well discussed.
    ____ Model used to estimate exposure for certain scenarios are missing important components.
    ____ Model used to estimate exposure is outdated.
    ____ Model used to estimate exposure for certain scenarios make assumptions that seem counter intuitive when measured by industrial experiences.
    ____ Exposure predictions for select scenarios are not compared to monitoring data available for those scenarios.
    ____ An analysis of the sensitivity to model inputs is not attempted or attempt is otherwise inadequate.
    ____ Monte Carlo exercise, if used, is not well defined, inadequately discussed, or too limited to fully describe expectations of occupational users' exposures for selected scenarios.
    ____ Distributions used in the Monte Carlo exercise are not properly described, statistics (e.g. mean, standard deviation, min, median, max, etc.) that identify the exact form of the distribution used are not provided.
    ____ In the Monte Carlo exercise, some variables are set to a constant when a distribution is expected.
    ____ Estimates presented in the Evaluation were unable to be duplicated by reviewers (e.g. ADC and LADCs) using the equations and values reported.
    ____ Unclear how model parameters were estimated given so few data points available.
    ____ Justification not provided for why certain monitoring data are not used when other (typically higher quality, more informative) data are ignored.
    ____ Sources of readily available data (OSHA, etc.) on factors impacting workers' exposures not acknowledged and not utilized.
    ____ Limited monitoring data are used to extrapolate exposures for scenarios where the data no longer are representative/appropriate.
    ____ Scenarios in which multiple exposure sources are likely do not calculate integrated exposures (aggregate exposure assessment).
    ____ Scenarios in which multiple exposure events (more than one exposure per worker per day) are not modeled and hence highest potential exposures are not realized in the analysis.
    ____ Exposure assessment for a scenario assumes workers will be using appropriate PPE when available information on industrial hygiene practice suggests otherwise.
    ____ Assumptions on engineering controls and work practices are not stated or statements are unclear.
    ____ Protection factors for gloves are assumed fixed when available information suggests that protection decreases as the glove ages and hence actual protection is always less than the stated (theoretical) protection factor.
    ____ Variability in use of PPE across sites (facilities) not discussed.
    ____ The Evaluation does not highlight those scenarios where safety margins are dependent on proper PPE usage.
    ____ Exposures from extended dermal uptake due to presence of chemical on/in work clothing not accounted for in analysis.
    ____ Dermal exposure assessment limited to hands when scenarios suggest skin of other body parts (arms, torso, etc.) will contact chemical during work tasks.
    ____ Aggregate exposures not consistently computed and included in subsequent risk assessment.
    ____ Inconsistent application of approaches and associated terminology related to dermal absorption modeling.
    ____ Acute exposure scenarios are not extreme enough to capture high-end or most impactful exposures (e.g. in the case the chemical is an irritant, high-end acute exposures of less than 8 hr. may be of most interest).
    ____ Chronic exposure scenarios do not consider long enough exposure periods to capture longest exposed.
    ____ For chemicals where genotype plays a role in individual susceptibility, the exposures to this genetically susceptible subpopulation is not discussed.
    ____ Uncertainties in (inhalation or dermal) exposure assessment not adequately discussed.
    ____ Assessment does not identify the route(s) of exposure that account for the largest fraction of workers' total exposure.
    ____ Inhalation-to-dermal extrapolation not fully discussed or justified.
    ____ Unclear when there is enough good quality data to derive a sufficiently reliable estimate of exposure for specific scenarios.
    ____ Unclear how a medium reliability can be assigned to an exposure estimate under assumed PPE use when there is no information on glove use (one way or the other).
    ____ Rationale missing for why the default PPE protection factors can be assigned when the type, appropriateness, and proper use of PPE is not known. 
    ____ Assumption that dermal absorption can be well-represented as a fixed fraction is not grounded in good science.
    ____ Results for relatively simple in vitro skin absorption tests are not available.
       

 Occupational Non-Users Exposure:

    ____ Worker and ONU exposures not sufficiently distinguished or contrasted.
    ____ Available (monitoring) data on ONU exposures not used in assessment.
    ____ Justification for the assumption that ONU exposures are less than worker exposures not provided or otherwise inadequate.
    ____ Assumption that the representative exposure level for ONUs is best determined as the central tendency (mean/median) exposures for occupational users is not or poorly justified.
    ____ Distance of ONU work locations from release sources not accounted for in assessing ONU exposures.

 Consumer Exposure:

    ____ Presence of chemical in general population surveillance programs unexplained by consumer exposure scenarios used in the evaluation.
    ____ Assumptions used in the modeling of consumer exposures from some scenarios are not well described.
    ____ Assumptions used in the modeling of consumer exposures are inadequate in that they do not correspond to facts extracted from currently available information.
    ____ Some reasonably foreseen scenarios (COUs) are excluded or not discussed.
    ____ Some consumer exposure scenarios (COUs) are not well described/documented (in particular assumptions on dermal exposures).
    ____ Some consumer exposure scenarios are no longer possible since products are no longer available to consumers.
    ____ Exposures to non-occupational bystanders (e.g. those living adjacent to release sites) do not seem to be considered or discussed.

 Human Health Hazard:

    ____ Healthy worker effect and associated biases inadequately discussed and/or accounted for in the evaluation.
    ____ Data on the lethality of the chemical to humans not fully accounted for in the evaluation.
    ____ Available human data provide no information on the potential of experiencing certain adverse health outcomes predicted from animal studies (e.g. reproductive or developmental toxicity)
    ____ Results from limited human studies do not support or refute an association between exposures and increased risk of experiencing adverse health conditions, including cancer.
    ____ Not all effects on humans (such as allergic reactions, skin/nasal/throat/lung irritation, burns, etc.) acknowledged or discussed in the evaluation.
    ____ Acute point of departure (POD) based on a small biological effect of questionable significance.
    ____ Even though an adequate and validated PBPK-PD model is available for the chemical, model results are not used in determining the POD.
    ____ The description of the PBPK-PD model used is inadequate.
    ____ Uncertainty factors used are poorly justified and/or inadequate to account for extent and impact of uncertainties.
    ____ Best available science not used in setting uncertainty factors.
    ____ Some uncertainty factors (e.g. database) are not discussed, and lack of consideration not justified.
    ____ Relevance of animal data to human health hazard not clear or described.
    ____ Certain important human health endpoints (e.g. immunotoxicity, myocardial effects, reproductive and developmental effects, breast cancer) not considered or considered and inappropriately dismissed.
    ____ Potential mechanisms of action not discussed 
    ____ The choice of key mode of action/mechanisms among a suite of potential equi-plausible MOAs is not justified.
    ____ Dose response model results from available epidemiological studies not compared to similar results from animal studies.
    ____ The decision to NOT use the adverse health endpoint calculated to have highest risk is not adequately justified.
    ____ Links between exposures and cancers used to establish the target POD are poorly described 
    ____ Links between exposures and cancers used to establish the target POD is weakly supported by available data and uncertainty factors inadequate to account for this.
    ____ In vitro genotoxicity findings used to estimate equivalent in vivo exposures use an extrapolation that has not been discussed or adequately justified.
    ____ Weight of evidence arguments are not clearly described or otherwise inadequate.
    ____ Assumptions used in the dose-response modeling not well justified or discussed.
    ____ BMDL modeling inadequate, does not follow established guidance, or poorly documented.
    ____ The selected mode of action or mechanisms is not based on current published science.
    ____ The impact of possible non-genotoxic mode of action is not discussed or analyzed.

 Risk Characterization:

    ____ Evaluation is not explicit and consistent in the identification of data that has been deemed usable for the determination of exposures and risks.
    ____ The likelihood that workers may not utilize provided and required PPE is not discussed as be part of the final risk characterization.
    ____ Not consistent in using the term "no unacceptable risk" and sometimes uses the inexact expression - "no risk".
    ____ In appropriately suggesting that observing low risk for central tendency and high-end exposures somehow increases confidence in results.

 6. Content and Organization:

    ____ Assumptions in general are not clearly presented or properly justified.
    ____ Citations are inconsistent with the same document being cited under multiple labels (e.g. Hoeschst Celanese Corporation, 1992 is also referred to as Gibbs, 1992).
    ____ Risk conclusions not summarized at the beginning of the risk characterization section.
    ____ Risk determinations not extrapolated back to exposure sites (facilities) and number of sites and/or workers at risk not identified.
    ____ Risk characterization and determination in the current evaluation not compared to those of past assessments (past assessments are listed).
    ____ Summary graphics (e.g. concept maps, bar charts, etc.) are not provided to help readers grasp extent and impact of findings. 
    ____ It is unclear what reasonably available information means in the context of this evaluation.