Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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## Draft Residual Risk Assessment for the Flexible Polyurethane Foam Production Source Categor y

by EPA’s Office of Air Quality Planning and Standards Office of Air and Radiation August 2013Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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### Table of Contents

1 Introduction

................................ ................................ ................................ ........................ 4 2 Methods

................................ ................................ ................................ .............................. 5 2.1 Emissions and source data

................................ ................................ ........................... 5 2.2 Dispersion modeling for inhalation exposure assessment

................................ ........... 5 2.3 Estimating human inhalation exposure

................................ ................................ ....... 8 2.4 Acute Risk Screening and Refined Assessments

................................ ........................ 9 2.5 Multipathway and environmental risk screening

................................ ...................... 10 2.6 Dose

- Response Assess ment

................................ ................................ ...................... 11 2.6.1 Sources of chronic dose

- response information

................................ .................. 12 2.6.2 Sources of acute dose

- response information

................................ ...................... 17 2.7 Risk Characterization

................................ ................................ ................................ 20 2.7.1 General

................................ ................................ ................................ ............... 20 2.7.2 Mixtures

................................ ................................ ................................ ............. 22 3 Risk Results

................................ ................................ ................................ .................. 23 3.1 Source Category Description and Results

................................ ................................ . 23 3.2 Risk Char acterization

................................ ................................ ................................ 24 4 General Discussion of Uncertainties and How They Have Been Addressed

................... 28 4 .1 Exposure Modeling Uncertainties

................................ ................................ ............. 28 4 .2 Uncertainties in the Dose

- Response Relationships

................................ ................... 29 5 References

................................ ................................ ................................ ........................ 38

Index of Tables

Table 2.2

- 1 AERMOD version 11103 model options for RTR modeling

................................ 6 Table 2.6

- 1 (a) Dose

- Response Values for Chronic Inhalation Exposu re to Carcinogens

.... 16 Table 2.6

- 1 (b) Dose

- Response Values for Chronic Inhalation Exposure to Noncarcinogens

................................ ................................ ................................ ................................ .................. 17 Table 2.6

- 2 Do se

- Response Values for Acute Exposure

................................ ........................ 20 Table 3.1

- 1 Summary of Emissions from the Flexible Polyurethane Foam Production Category and Availability of Dose

- Response Values

................................ .............................. 24 Table 3.2

- 1 Summary of Source Category Level Inhalation Risks for Flexible Polyurethane Foam Production

................................ ................................ ................................ ...................... 26

Appendices

Appendix 1 Development of the RTR Emissions Dataset for the Flexible Polyurethane Foam Production Source Category Appendix 2 Technical Support Document for HEM 3 Modeling Appendix 3 Meteorological Data for HEM 3 Modeling Appendix 4 Analysis of data on short

- term emission rates relative to long

- term emission
rate sDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Appendix 5 Technical Support Document for TRIM

- Based Multipathway Screening Scenario for RTR: Summary of Approach and Evaluation Appendix 6 Detailed Risk Modeling Results

Index of Acronyms AERMOD American Meteorological Society/EPA Regulatory Model AEGL Acute exposure guideline level ASTDR US Agency for Toxic Substances and Disease Registry CalEPA California Environmental Agency ERPG Emergency Response Planning Guideline HAP Hazardous Air Pollutant HEM Human Exposure Model HI Hazard index HQ Hazard quotient IRIS Integrated Risk Information System MACT Maximum Achievable Control Technology MIR Maximum Individual Risk MOA Mode of action NAC National Advisory Committee NAAQS National Ambient Air Quality Standard NATA National Air Toxics Assessmen t NEI National Emissions Inventory NPRM Notice of Proposed Rulemaking PB

- HAP Persistent and Bioaccumulative

- HAP POM Polycyclic organic matter REL Reference exposure level RfC Reference concentration RfD Reference dose RTR Risk and Technology TOSHI Target

- organ

- specific hazard index URE Unit risk estimateDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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## 1 Introduction

Section 112 of the Clean Air Act (CAA) establishes a two

- stage regulatory process for addressing emissions of hazardous air pollutants (HAPs) from stationary sources. In the first stage, section 112(d) requires the Environmental Protection Agency (EPA, or the Agency) to develop technology

- based standards for categories of sources (e.g., petroleum refineries, pulp and paper mills, etc.) [ 1 ]. EPA has largely completed the initial Max imum Achievable Control Technology ( MACT ) standards as required under this provision. Under section 112(d)(6), EPA must review each of these technology

- based standards at least every eight years and revise a standard, as necessary, “taking into account de velopments in practices,
processe s and control technologies.” In the second stage, EPA is required under section 112(f)(2) to assess the health and environmental risks that remain after implementation of the MACT standards. If additional risk reductions are necessary to protect public health with an ample margin of safety or to prevent an adverse environmental effect, EPA must develop standards to address these remaining risks. This second stage of the regulatory process is known as the residual risk sta ge. For each source category for which EPA issued MACT standards, the residual risk stage must be completed within eight years of promulgation of the initial technology

- based standard.

In December of 2006 we consulted with a panel from the EPA's Science Advisory Board (SAB) on the “Risk and Technology Review (RTR) Assessment Plan” and in June of 2007, we received a letter with the results of that consultation. Subsequent to the consultation, in July of 2009 a meeting was held with an SAB panel for a form al peer review of the “Risk and Technology Review (RTR) Assessment Methodologies” [ 2 ]. We received the final SAB report on this review in May of 2010 [ 3 ]. Where appropriate, we have responded to the key messages from this review in developing our current risk assessment s and we will be continuing our efforts to improve our assessments by incorporating updates based on the SAB recommendations as they are developed and become available . Our responses to the key recommendations of the SAB are outlined in th e memo entitled, “EPA’s Actions in Response to Key Recommendations from the SAB Review of RTR risk Assessment Methodologies” [ 4 ].

This document contains the methods and the results of baseline risk assessments (i.e., after the implementation of the respe ctive MACT standards) performed for the Flexible Polyurethane Foam Production Category . The methods discussion includes descriptions of the methods used to develop refined estimates of chronic inhalation exposures and human health risks for cancer and non cancer endpoints, as well as descriptions of the methods used to screen for acute health risks, chronic non

- inhalation health risks, and adverse e nvironmental effects.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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## 2 Methods

2.1 Emissions and source data
The F lexible P olyurethane F oam P roduction source c ategory includes facilities manufacturing flexible polyurethane foam. Specifically, the rule targets three distinct segments of this industry: slabstock, molded, and rebond polyurethane foam production. Potential hazardous air pollutant (HAP) emission sou rces at foam production facilities depend on the type of foam being produced. Generally, air toxics are released from reactants, auxiliary blowing agents, solvents, adhesives, equipment cleaners, and other chemicals used in the manufacturing of these mater ials. A complete description of the flexible polyurethane foam production source category can be found in the text of the NPRM.

W e currently estimate that there are approximately 13 Flexible Polyurethane Foam p roduction facilities subject to the MACT sta ndards : 7 S labstock, 6 molded, and 2 rebond. Both rebond facilities are co

- located with either a slabstock or molded foam facil ity. The NPRM data set contains these 13 facilities identified with a MACT code 1314 in the 2005 National

- scale Air Toxics Asses sment (NATA) National Emissions Inventory (NEI). The 2005 NATA NEI was updated for this category with data from industry and enhanced quality assurance of facility and emission locations

. The emissions for the Flexible Polyurethane Foam Production source category NPRM data set (of 13 facilities) are summarized in Table 2

- 1 . The total HAP emissions for the source category are approximately 1 ton per year. Based on these data, the HAP emitted in the largest quantities across these 13 facilities are 2,4

- tolu ene diisocyanate, propylene oxide, and toluene. These 3 chemicals account for 9 3 percent of the total emissions by mass. No persistent and bioaccumulative HAP (PB HA P) 1 are reported as emissions from the 13 facilities in the Flexible Polyurethane Foam Pr oduction source category. The emissions data and risk assessment inputs for the FPUF production source category are described further in Appendix 1, “ Development of the RTR Emissions Dataset for the Flexible Polyurethane Foam Production Source Category .”



### 2.2 Dispersion modeling for inhalation exposure assessment Both long

- and short

- term inhalation exposure concentrations and associated health risk from each facility in the source category of interest were estimated using the Human Exposure Model in combinatio n with the American Meteorological Society/EPA Regulatory Model (AERMOD) dispersion modeling system (HEM 3 ). The approach used in applying this modeling system is outlined below, and further details are provided in Appendix 2

. The HEM 3 performs three main operations: atmospheric dispersion modeling, estimation of individual human exposures and health risks, and estimation of population risks. This section focuses on the dispersion modeling component. The exposure and risk characterization components are discussed in other subsections of Sections 2 and 3.

1 Persistent and bio accumulative HAP are defined in the EPA’s Air Toxics Risk Assessment Library , Volume 1, EPA

- 453K

- 04

- 001A, as referenced in the NPRM and provided on the EPA’s Technology Transfer Network website for Fate, Exposure, and Risk Assessment at http://www.epa.gov/ttn/fera/risk_atra_vol1.html

.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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The dispersion model in the HEM 3 system, AERMOD version 11103 , is a state

- of

- the

science Gaussian plume dispersion model that is preferred by EPA for modeling point, area, and volume sources of continuou s air emissions from facility applications [ 5 ]. Further details on AERMOD can be found in the AERMOD Users Guide [ 6 ]. The model is used to develop annual average ambient concentrations through the simulation of hour

- by

- hour dispersion from the emission s ources into the surrounding atmosphere. Hourly emission rates used for this simulation are generated by evenly dividing the total annual emission rate from the inventory into the 8,760 hours of the year.

The first step in the application of the HEM 3 mode ling system is to predict ambient concentrations at locations of interest. The AERMOD model options employed are summarized in Table 2.2

- 1 and are discussed further below.

Table 2.2

- 1 AERMOD version 11103 m o del options for RTR modeling

Modeling Option Selected Parameter for chronic exposure

Type of calculations Hourly Ambient Concentration

Source type Point

Receptor orientation Polar (13 rings and 16 radials) Discrete (census block centroids)

Terrain characterization Actual from USGS 1 /3 Arc Second NED data

Building downwash Not Included

Plume deposition/depletion Not Included

Urban source option No

Meteorology 1 year representative NWS from nearest site ( over 8 00 stations)

In HEM 3 , meteorologica l data are ordinarily selected from a list of over 824 National Weather Service (NWS) surface observation stations across the continental United States, Alaska, Hawaii, and Puerto Rico. In most cases the nearest station is selected as representative of th e conditions at the subject facility. Ideally, when considering off

- site meteorological data most site specific dispersion modeling efforts will employ up to five years of data to capture variability in weather patterns from year to year. However, becaus e we had an insufficient number of appropriately formatted model input files derived from available meteorological data, we modeled only a single year, typically 2011 . While the selection of a single year may result in under

- prediction of long

- term ambien t levels at some locations, likewise it may result in over

- prediction at others. For each facility identified by its characteristic latitude and longitude coordinates, the closest meteorological station was used in the dispersion modeling. The average di stance between a modeled facility and the applicable meteorological station was 52 miles ( 84 km). Appendix 3 (Meteorological Data Processing Using AERMET for HEM 3 ) provides a complete listing of stations andDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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assumptions along with further details used in processing the data through AERMET. The sensitivity of model results to the selection of the nearest weather station and the use of one year of meteorological data is discussed in “Risk and Technology Review (RTR) Risk Assessment Methodologies” [ 2 ].

The HEM 3 system estimates ambient concentrations at the geographic centroids of census blocks (using the 20 1 0 Census), and at other receptor locations that can be specified by the user. The model accounts for the effects of multiple facilities when estimating concentration impacts at each block centroid. Typically we combined only the impacts of facilities within the same source category, and assessed chronic exposure and risk only for census blocks with at least one resident (i.e., locations where people may reasonably be assumed to reside rather than receptor points at the fenceline of a facility). Chronic ambient concentrations were calculated as the annual average of all estimated short

- term (one

- hour) concentrations at each block centroid. Possible futu re residential use of currently uninhabited areas was not considered. Census blocks, the finest resolution available in the census data, are typically comprised of approximately 40 people or about ten households.

In contrast to the development of ambi ent concentrations for evaluating long

- term exposures, which was performed only for occupied census blocks, worst

- case short

- term (one

- hour) concentrations were estimated both at the census block centroids and at points nearer the facility that represent l ocations where people may be present for short periods, but generally no nearer than 100 meters from the center of the facility (note that for large facilities, this 100

- meter ring could still contain locations inside the facility property). Since short

- t erm emission rates were needed to screen for the potential for hazard via acute exposures, and since the emissions data contains only annual emission totals, we generally apply the assumption to all source categories that the maximum one

- hour emission rate from any source is ten times the average annual hourly emission rate for that source.

The average hourly emissions rate is defined as the total emissions for a year divided by the total number of operating hours in the year. The choice of a factor of te n for acute screening was originally based on engineering judgment

. To develop a more robust peak

- to

- mean emissions factor, and in response to one of the key messages from the SAB consultation on our RTR Assessment Plan, we performed an analysis using a s hort

- term emissions data set from a number of source s located in Texas (originally reported on by Allen et al

. 2004)[ 7 ]. In that report, the Texas Environmental Research Consortium Project compared hourly and annual emissions data for volatile organic comp ound s for all facilities in a heavily

industrialized 4

- county area (Harris, Galveston, Chambers, and Brazoria Counties , TX) over an eleven

- month time period in 2001 . We obtained the dataset and performed our own analysis, focusing that analysis on sources which reported emitting high quantities of HAP over short periods of time (see Appendix 4

, Analysis of data on short

- term emission rates relative to long

- term emission rates ). Most peak emission events were less than twice the annual average, the highest was a factor of 74 times the annual average , and the 99 th percentile ratio of peak hourly emission rate to the annual hourly emission rate was 9 . Based on these results, we typically chose a factor of ten for the initial screening . These factors are int ended to cover all possible hourly peaks associated with routinely

- variable emissions. While there have been some documented emission excursions above this level, our analysis ofDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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the data from the Texas Environmental Research Consortium suggests that this factor should cover more than 99% of the short

- term peak gaseous or volatile HAP emissions from typical industrial sources.

Census block elevations for HEM 3 modeling were determined nationally from the US Geological Service 1 /3 Arc Second National El evation Dataset , which have a spatial resolution of about 1 0 meters. Elevations of polar grid points used in estimating short

- and long

- term ambient concentrations were assumed to be equal to the highest elevation of any census block falling within the po lar grid sector corresponding to the grid point. If a sector does not contain any blocks, the model defaults the elevation to that of the nearest block. If an elevation is not provided for the emission source, the model uses the average elevation of all sectors within the innermost model ring.

In addition to using receptor elevation to determine plume height, AERMOD adjusts the plume’s flow if nearby elevated hills are expected to influence the wind patterns. For details on how hill heights were estima ted and used in the AERMOD modeling

, see Appendix 2

.



### 2.3 Estimating human inhalation exposure
We used the estimated annual average ambient air concentration of each HAP at each census block centroid as a surrogate for the lifetime inhalation exposure conce ntration of all the people who reside in the census block. That is, the risk analysis did not consider either the short

- term or long

- term behavior (mobility) of the exposed populations and its potential influence on their exposure.

We did not address s hort

- term human activity for two reasons. First, our experience with the NATA assessments (which modeled daily activity using EPA’s HAPEM model) suggests that, given our current understanding of microenvironment concentrations and daily activities, model ing short

- term activity would, on average, reduce risk estimates about 25% for particulate HAP; it will also reduce risk estimates for gaseous HAP, but typically by much less. Second, basing exposure estimates on average ambient concentrations at census b lock centroids may underestimate or overestimate actual exposure concentrations at some residences. Further reducing exposure estimates for the most highly exposed residents by modeling their short

- term behavior could add a systematic low bias to these re sults.

We did not address long

- term migration nor population growth or decrease over 70 years, instead basing the assessment on the assumption that each person’s predicted exposure is constant over the course of their lifetime which is assumed to be 70 ye ars. In assessing cancer risk, we generally estimated three metrics; the maximum individual risk (MIR), which is defined as the risk associated with a lifetime of exposure at the highest concentration; the population risk distribution; and the cancer inci dence. The assumption of not considering short or long

- term population mobility does not bias the estimate of the theoretical MIR nor does it affect the estimate of cancer incidence since the total population number remains the same. It does, however, af fect the shape of the distribution of individual risks across the affected population, shifting it toward higher estimated individual risks at the upper end and reducing the number of people estimated to be at lower risks, thereby increasing the estimated number of people at specific risk levels

.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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When screening for potentially significant acute exposures, we used an estimate of the highest hourly ambient concentration at any off

- site location as the surrogate for the maximum potential acute exposure conc entration for any individual.



### 2.4 Acute Risk Screening and Refined Assessments In establishing a scientifically defensible approach for the assessment of potential health risks due to acute exposures to HAP, we f ollowed the same general approach that has been used for developing chronic health risk assessments under the residual risk program. That is, we developed a tiered, iterative approach. This approach to risk assessment was endorsed by the National Academy of Sciences in its 1993 publication “Science an d Judgment in Risk Assessment” and subsequently was adopted in the EPA’s “Residual Risk Report to Congress” in 1999.

The assessment methodology is designed to eliminate from further consideration those facilities for which we have confidence that no acu te adverse health effects of concern will occur. To do so, we use what is called a tiered, iterative approach to the asse ssment. This means that we begin with a screening assessment, which relies on readily available data and uses conservative assumption s that in combination approximate a worst

- case exposure . The result of this screening process is that either the facility being assessed poses no potential acute health risks (i.e., it “screens out”), or that it requires further , more refined assessment. A more refined acute assessment could u s e industry

- or site

- specific data on the temporal pattern of emissions, the layout of emission points at the facility, the boundaries of the facility, and /or the local meteorology. In some cases, all of these site

- specific data are used to refine the assessment; in others, lesser amount s of site

- specific data can be used to determine that acute exposures are not a concern, and significant additional data collection is not necessary.

Acute health risk screening wa s performed as the first step. We used conservative assumptions for emission rates, meteorology, and exposure location. We used the following
worst

- case assumptions in our screening approach:

• Peak 1

- hour emissions were assumed to equal 10 times the aver age 1

- hour emission
rates.

• For facilities with multiple emission points, peak 1

- hour emissions were assumed to occur at all emission points at the same time.

• For facilities with multiple emission points, 1

- hour concentrations at each receptor were assumed to be the sum of the maximum concentrations due to each emission point, regardless of whether those maximum concentrations occurred during the same hour.

• Worst

- case meteorology (from one year of local meteorology) was assumed to occur at the same time the peak emission rates occur. The recommended EPA local

- scale dispersion model, AERMOD, is used for simulating atmospheric dispersion.

• A person was assumed to be located downwind at the point of maximum impact during this same worst

- case 1

- hour period, but no nearer to the source than 100
meters.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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• The maximum impact was compared to multiple short

- term health benchmarks for the HAP being assessed to determine if a possible acute health risk might exist. These benchmarks are described in section 2.6 of this re port.

As mentioned above, when we identify acute impacts which exceed their relevant benchmarks, we pursue refining our acute screening estimates. For the Flexible Polyurethane Foam Production source category data were not available to develop a refined emissions multiplier, therefore, the default emissions multiplier of 10 was used.



### 2.5 Multipathway and environmental risk screening The potential for significant human health risks due to exposures via routes other than inhalation (i.e., multipathway exposure s) was screened by first determining whether any sources emitted any hazardous air pollutants known to be persistent and bioaccumulative in the environment (PB

- HAP). The PB

- HAP compounds or compound classes are identified for the screening from the EPA’s Air Toxics Risk Assessment Library [ 8 ]. Examples of PB

- HAP

are cadmium compounds, chlordane, chlorinated dibenzodioxins and furans, DDE, heptachlor, hexachlorobenzene, hexachlorocyclohexane, lead compounds, mercury compounds, methoxychlor, polychlorinated biphenyls, polycyclic organic matter (POM)

, toxaphene, and trifluralin

. There are no PB

- HAP e missions in the Flexible Polyurethane Foam Production source categor y

.

PB

- HAP emissions , if emitted, are evaluated for potential non

- inhalation risks and adve rse environmental impacts using our screening scenario which was developed for use with the TRIM.FaTE 2 model. This screening scenario uses environmental media outputs from the
peer

- reviewed TRIM.FaTE to estimate the maximum potential ingestion risks for a ny specified emission scenario by using a generic farming/fishing exposure scenario that simulates a subsistence environment. The screening scenario retains many of the ingestion and scenario inputs developed for EPA’s Human Health Risk Assessment Protoco ls (HHRAP) for hazardous waste combustion facilities. 3 In the development of the screening scenario a sensitivity analysis was conducted to ensure that its key design parameters were established such that environmental media concentrations were not undere stimated, and to also minimize the occurrence of false positives for human health endpoints. See Appendix 5 for a complete discussion of the development and testing of the screening scenario, as well as for the values of facility

- level emission rates deve loped for screening potentially significant multi

- pathway impacts. For the purpose of developing emission rates for our multi

- pathway screening, we derived emission levels for each PB HAP at which the maximum human health risk would be 1 in a million for lifetime cancer risk or a hazard quotient of 1.0 for noncancer impacts.

In evaluating the potential multi

- pathway risks from emissions of lead compounds, rather than developing a screening emission rate for them , we compared maximum estimated chronic
at mospheric concentrations with the current National Ambient Air Quality Standard

2 EPA’s Total Risk Integrated Methodology (General Information) http://epa.gov/ttn/fera/trim_gen.html
3 EPA’s Human Health Risk Assessment Protocol (HHRAP) for Hazardous Waste Combustion Facilities; http://www.epa.gov/epaoswer/hazwaste/combust/riskvol.htm#volume1Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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(NAAQS) for lead. Values below the NAAQS were considered to have a low potential for multi

- pathway risks.

Since n one of the facilities in the Flexible Polyurethane Foam Produ ction source categor y reported emissions of PB HAP an assessment of multi

- pathway exposures

. In section 3 we present our inhalation exposure results separate from the multipathway screening assessment results , if conducted . We have been questioned as t o why we do not add these two risk results together. We do not believe it is appropriate to add a multipathway screening result to a refined quantitative inhalation risk result. The purpose of the multipathway screen is not to provide a quantitative valu e. This multipathway screening approach is designed to point out facilities and pollutants that we are confident do not have a multipathway effect and for those that do not screen out, more effort can be focused on them. The multipathway screening scenar io is a hypothetical scenario that does not have a real

world counterpart. The real world result would be less than the screening result value, but we cannot say how much less it would be. In addition, the inhalation assessment is quite refined and the m ultipathway screen is a less rigorous assessment. It might be mathematically logical to add these values together, but it is not scientifically appropriate. It is also highly unlikely that the receptor exposed to the maximum inhalation risk is also the r eceptor exposed to the maximum multipathway risk. Therefore, we do not believe that it is appropriate to sum the inhalation risk assessment results and the multipathway screening result. However, in certain cases where we perform a refined multipathway a ssessment on facilities that have failed the Tier 1 and Tier 2 multipathway screen it may be appropriate to combine this refined multipathway result with the inhalation result. Compatibility is a major factor in deciding the appropriateness of combining t he two risk results. For instance if the refined multipathway risk results and the inhalation results are associated with the same target organ (e.g. liver cancer) then it may be appropriate to add the results together. It should be noted that any decisi on to add these results will bring additional new uncertainties into the assessment.

Since none of the facilities in the Flexible Polyurethane Foam Production source category reported emissions of any environmental HAP included in our environmental risk screen (i.e., lead, dioxins, cadmium, mercury, PAHs, HCL, and HF) an environmental risk screen was not performed.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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### 2.6 Dose

- Response Assessment

2.6.1 Sources of chronic dose

- response information
Dose

- response assessment (carcinogenic and non

- carcinogenic) for c hronic exposure (either by inhalation or ingestion) for the HAPs reported in the emissions inventories for Flexible Polyurethane Foam Production sources were based on the EPA Office of Air Quality Planning and Standards’ existing recommendations for HAPs [ 9 ], also used for NATA [ 10 ]. This information has been obtained from various sources and prioritized according to (1) conceptual consistency with EPA risk assessment guidelines and (2) level of peer review received. The prioritization process was aimed at incorporating into our assessments the best available science with respect to dose

- response information. The recommendations are based on the following sources, in order of priority :

1) US Environmental Protection Agency (EPA). EPA has developed dose

- res ponse assessments for chronic exposure for many of the pollutants in this study. These assessments typically provide a qualitative statement regarding the strength of scientific data and specify a reference concentration (RfC, for inhalation) or reference dose (RfD, for ingestion) to protect against effects other than cancer and/or a unit risk estimate (URE, for inhalation) or slope factor (SF, for ingestion) to estimate the probability of developing

cancer. The RfC is defined as an “ estimate (with uncert ainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. ” The RfD is “a n estimate ( with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. ” The URE is defined as “ t he upper

- bound excess cancer risk estimated to result from continuous lifetime exposure to an agent at a concentration of 1 μg/m 3 in air. ” The SF is “a n upper bound, approximating a 95% confidence limit, on the increased cancer risk from a lifetime exposu re to an agent. This estimate, [is] usually expressed in units of proportion (of a population) affected per mg/kg

- day ...” EPA disseminates dose

- response assessment information in several forms, based on the level of review. The Integrated Risk Information System (IRIS) [ 11 ] is an EPA database that contains scientific health assessment information, including dose

- response information. All IRIS assessments since 1996 have also undergone independent external peer review. The current IRIS process includes revie w by EPA scientists, interagency reviewers from other federal agencies, and the public, and peer review by independent scientists external to EPA. New IRIS values are developed and old IRIS values are updated as new health effects data become available. Refer to the “IRIS Track” website for detailed information on status and scheduling of current individual IRIS assessments and updates ( http://cfpub.epa.gov/ncea/iristrac/index.cfm ). EPA’s scien ce policy approach , under the current carcinogen guidelines, is to use linear low

- dose extrapolation as a default option for carcinogens for which the mode of action (MOA) has not been identified. We expect future EPA dose

- response assessments to identify nonlinear MOAs where appropriate, and we will use those analyses (once they are peer reviewed) in our risk assessments. AtDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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this time, however, there are no available carcinogen dose

- response assessments for inhalation exposure that are based on a nonline ar MOA

.
2) US Agency for Toxic Substances and Disease Registry (ATSDR). ATSDR, which is part of the US Department of Health and Human Services, develops and publishes Minimum Risk Levels (MRLs) [ 12 ] for inhalation and oral exposure to many toxic substances. As stated on the ATSDR web site: “ Following discussions with scientists within the Department of Health and Human Services (HHS) and the EPA, ATSDR chose to adopt a practice similar to that of the EPA's Reference Dose (RfD) and Reference Concentration (Rf C) for deriving substance specific health guidance levels for non neoplastic endpoints .” The MRL is defined as “an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (other than cancer) over a specified duration of exposure.” ATSDR describes MRLs as substance

- specific estimates to be used by health assessors to select environmental contaminants for further evaluation. Exposures above an MRL do not necessarily represent a threat, and MRLs ar e therefore not intended for use as predictors of adverse health effects or for setting cleanup levels.

3) California Environmental Protection Agency (CalEPA). The CalEPA Office of Environmental Health Hazard Assessment has developed dose

- response assessmen ts for many substances, based both on carcinogenicity and health effects other than cancer. The process for developing these assessments is similar to that used by EPA to develop IRIS values and incorporates significant external scientific peer review. A s cited in the CalEPA Technical Support Document for developing their chronic assessments 4 : “The guidelines for developing chronic inhalation exposure levels incorporate many recommendations of the U.S. EPA [ 13 ] and NAS [ 14 ].” The non

- cancer information inc ludes available inhalation health risk guidance values expressed as chronic inhalation reference exposure levels (RELs) [ 15 ]. CalEPA defines the REL as “the concentration level at or below which no health effects are anticipated in the general human popula tion.” CalEPA's quantitative dose

- response information on carcinogenicity by inhalation exposure is expressed in terms of the URE [ 16 ], defined similarly to EPA's URE.

In developing chronic risk estimates, we adjusted dose

- response values for some HAPs based on professional judgment, as follows:

1) In the case of HAP categories such as glycol ethers and cyanide compounds, the most conservative dose

- response value of the chemical category i s used as a surrogate for other compounds in the group f or which d ose

- response values are not available. This i s done in order to examine, under conservative assumptions, whether these HAPs that lack dose

response values may pose an unacceptable risk and require further examination, or screen
out from further assessment

.

4 Air Toxics Hot Spots Program, Risk Assessment Guidelines, Part III

- Technical Support Document for the Determination of Non

- cancer Chronic Reference Exposure Levels. Air Toxicology and Epidemiology Section, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. February 2000 ( http://www.oehha.ca.gov/air/chronic_rels/pdf/relsP32k.pdf )Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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2) Where possible for emissions of unspecified mixtures of HAP categories such as met al compounds and POM, we apply category

- specific chemical speciation profiles appropriate to the source category to develop a composite dose

- response value for the catego ry.

3) In 2004, the EPA determined that the Chemical Industry Institute of Toxicology (CIIT) cancer dose

- response value for formaldehyde (5.5 x 10 - 9 per μg/m 3 ) was based on better science than the IRIS cancer dose

- response value (1.3 x 10 - 5 per μg/m 3 ), and we switched from using the IRIS value to the CIIT value in risk assessments supporting regulatory actions. S ubsequent research published by EPA su ggested that the CIIT model was not appropriate and in 2010 EPA returned to using 1991 IRIS value

. EPA has been working on revising the formaldehyde IRIS assessment and the National Academy of Sciences (NAS) completed its review of the EPA’s draft assessm ent in April of 2011

. 5 EPA will follow the NAS Report recommendations and will present results obtained by implementing the biologically

- based dose

- response (BBDR) model for formaldehyde. EPA will compare these estimates with those currently presented in the External Review draft of the assessment and will discuss their strengths and weaknesses. As recommended by the NAS committee, appropriate sensitivity and uncertainty analyses will be an integral component of implementing the BBDR model. The draft IRI S assessment will be revised in response to the NAS peer review and public comments and the final assessment will be posted on the IRIS database. In the interim, we will present findings using the 1991 IRIS value as a primary estimate and EPA may also con sider other information as the science evolves.

4) In the case of nickel compounds, to provide a health

- protective estimate of potential cancer risks, we used the IRIS URE value for nickel subsulfide in this assessment. Based on past scientific and technica l considerations, the determination of the percent of nickel subsulfide was considered a major factor for estimating the extent and magnitude of the risks of cancer due to nickel

- containing emissions. Nickel speciation information for some of the largest nickel

- emitting sources (including oil combustion, coal combustion, and others) suggested that at least 35 percent of total nickel emissions may be soluble compounds and that the URE for the mixture of inhaled nickel compounds (based on nickel subsulfide, and representative of pure insoluble crystalline nickel) could be derived to reflect the assumption that 65 percent of the total mass of nickel may be carcinogenic. Based on consistent views of major scientific bodies (i.e., National Toxicology Program (N TP) in their 12 th Report of the Carcinogens (ROC) 6 , International Agency for Research on Cancer (IARC) 7 , and other international agencies) 8 that consider all nickel compounds to be carcinogenic, we currently consider all nickel compounds to have the potent ial of being as carcinogenic to humans. The 12 th Report of the Carcinogens states that the

5 http://www.nap.edu/catalog.php?record_id=13142
6 National Toxicology Program (NTP), 2011. Report on carcinogens. 12 th ed. Research Triangle Park, NC: US Department of Health and Human Services (DHHS), Public Health Service. Available online at http://ntp.niehs.nih.gov/ntp/roc/twelfth/roc12.pdf
7 International Agency for Research on Cancer (IARC), 1990. IARC monographs on the evaluation of carcinoge nic risks to humans. Chromium, nickel, and welding. Vol. 49. Lyons, France: International Agency for Research on Cancer, World Health Organization Vol. 49:256.
8 World Health Organization (WHO, 1991) and the Europea n Union’s Scientific Committee o n Heal th and Environmental Risks (SCHER, 2006)

.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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“combined results of epidemiological studies, mechanistic studies, and carcinogenic studies in rodents support the concept that nickel compounds generate nickel ion s in target cells at sites critical for carcinogenesis, thus allowing consideration and evaluation of these compounds as a single group.” Although the precise nickel compound (or compounds) responsible for the carcinogenic effects in humans is not always clear, studies indicate that nickel sulfate and the combinations of nickel sulfides and oxides encountered in the nickel refining industries cause cancer in humans (these studies are summarized in a review by Grimsrud et al., 2010 9 ). The major scientific bodies mentioned above have also recognized that there are differences in toxicity and/or carcinogenic potential across the different nickel compounds. In this inhalation risk assessment, to take a conservative approach, we have considered all nickel comp ounds to be as carcinogenic as nickel subsulfide and have applied the IRIS URE for nickel subsulfide without a factor to reflect the assumption that 100 percent of the total mass of nickel may be as carcinogenic as pure nickel subsulfide. In addition, giv en that there are two additional URE 10 values derived for exposure to mixtures of nickel compounds, as a group, that are 2

- 3 fold lower than the IRIS URE for nickel subsulfide, the EPA also considers it reasonable to use a value that is 50 percent of the IR IS URE for nickel subsulfide for providing an estimate of the lower end of the plausible range of cancer potency values for different mixtures of nickel compounds.

5) A substantial propo rtion of POM reported to EPA’s N ati onal E mission I nventory (NEI) is
not speciated into individua l compounds. As a result, it i s necessary to apply the same simplifying assumptions to assessment s that are used in NATA. [ 17 ] The NATA approach partitions POM into eight different non

- overlapping “groups” that a re modeled as separ ate pollutants. Each POM group comprises POM species of similar carcinogenic potency, for which we can apply the same URE.

5) A chronic screening level of 163 ug/m 3 was developed for carbonyl sulfide (COS) from a No Observed Adverse Effects Level (NOAEL) o f 200 ppm based on brain lesions and neurophysiological alterations in r odents. A more detailed discussion of the studies used to develop the COS chronic screening level is provided in Appendix 8. The screening level includes a total uncertainty factor ( UF) of 3,000: 10x for extrapolation for interspecies differences, 10x for consideration of intraspecies variability, 10x for extrapolation from subchronic to chronic duration, and 3x for database insufficiencies. See section 5 of this document for a detai led discussion of exposure modeling uncertainties.

9 Grimsrud TK and Andersen A. Evidence of carcinogenicity in humans of water

- soluble nickel salts. J Occup Med Toxicol 2010, 5:1

- 7. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868037/?tool=pubmed

10 Two UREs (other than the current IRIS values) have been derived for nickel compounds as a group: one developed by the California Department of Health Services ( http://www.arb.ca.gov/toxics/id/summary/nickel_tech_b.pdf ) and the other by the Texas Commission on Environmental Quality ( http://www.epa.gov/ttn/atw/nata1999/99pdfs/healtheffectsinfo.pdf ).Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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The chronic screening level for COS is used only as a screening level assessment to identify areas with significant inhalation risk potential. A high COS chronic risk based on the screening level does not necessarily indicate that further action is required.

The emissions inventory for the Flexible Polyurethane Foam Production source categor y includes emissions of 9 HAP with available chronic quantitative inhalation dose

- response values. These HAP, their dose

- response values, and the source of the values are listed in Tables 2.6

- 1 (a) and ( b ).

Table 2.6

- 1 (a) Dose

- Response Values for Chronic Inhalation Exposure to Carcinogens

URE (unit risk estimate for cancer) 11 = cancer risk per μg/m 3 of ave rage lifetime exposure. Sources: IRIS = EPA Integrated Risk Information System, CAL = California EPA Office of Environmental Health Hazard Assessment.

Pollutant CAS Number 12 URE 5 (1/μg/m3) Source

Propylene oxide 75569 0.0000037 IRIS 2,4

- Toluene diisocy anate 584849 0.000011 CAL Trichloroethylene 79016 0.0000048 IRIS

11 The URE is the upper

- bound excess cancer risk estimated to result from continuous lifetime exposure to an agent at a concentration of 1 μg/m 3 in air. URE’s are considered upper bound estimates meaning they represent a plausible upper limit to the true value.
12 Chemical Abstract Services identification number. For groups of compounds that lack a CAS number we have used a surrogate 3

- digi t identifier corresponding to the group’s position on the CAA list of HAPs.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Table 2.6

- 1 (b) Dose

- Response Values for Chronic Inhalation Exposure to Noncarcinogens RfC (reference inhalation concentration) = an estimate (with uncertainty spanning perhaps an

or der of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Sources: IRIS = EPA Integrated Risk Information System, CAL = California EPA Office of Environmental Human Health Assessment, ATSDR = US Agency for Toxic Substances Disease Registry, EPA OAQPS = EPA Office of Air Quality Planning and Standards. Pollutant CAS Number 6 RfC (mg/m3) Source 13

Diethanolamine 111422 0.003 CAL Dimethyl formamide 68122 0.03 IRIS

- M Methyl isobutyl ketone 108101 3 IRIS

- L/M 4,4'

- Methylene diphenyl diisocyanate 101688 0.0006 IRIS

- M Propylene oxide 75569 0.03 IRIS

- M 2,4

- Toluene diisocyanate 584849 0.00007 IRIS

- M Toluene 1088 83 5 IRIS

- H Trichloroethylene 79016 0.002 IRIS

- H Xylenes (mixed) 1330207 0.1 IRIS

- M

2.6.2 Sources of acute dose

- response information
Hazard identification and dose

- response assessment information for preliminary acute inhalation exposure assessments a re based on the existing recommendations of OAQPS for HAPs [ 18 ]

. Depending on availability, the results from screening acute assessments are compared to both “no effects” reference levels for the general public, such as the California Reference Exposure Le vels (RELs), as well as emergency response levels, such as Acute Exposure Guideline Levels (AEGLs) and Emergency Response Planning Guidelines (ERPGs), with the recognition that the ultimate interpretation of any potential risks associated with an estimated exceedance of a particular reference level depends on the definition of that level and any limitations expressed therein. Comparisons among different available inhalation health effect reference values (both acute and chronic) for selected HAPs can be fo und in a n EPA document [ 19 ].

California Acute Reference Exposure Levels (RELs ). The California Environmental Protection Agency (CalEPA) has developed acute dose

- response reference values for many substances, expressing the results as acute inhalation Refe rence Exposure Levels (RELs).

The acute REL ( http://www.oehha.ca.gov/air/pdf/acuterel.pdf ) is defined by CalEPA as

“ t he concentration level at or below which no adverse health effects are antici pated for a

13 The descriptors L (low), M (medium), and H (high) have been added for IRIS RfC values to indicate the overall level of confidence in the RfC value, as reported in IRIS.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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specified exposure duration [ 20 ]

. RELs are based on the most sensitive, relevant, adverse health effect reported in the medical and toxicological literature. RELs are designed to protect the most sensitive individuals in the population by the inclusion of margins of safety. Since margins of safety are incorporated to address data gaps and uncertainties, exceeding the REL does not automatically indicate an adverse health impact. ” Acute RELs are developed for 1

- hour (and 8

- hour) exposures. The values incorporate uncertainty factors similar to those used in deriving EPA’s Inhalation Reference Concentrations (RfCs) for chronic exposures (and, in fact, California also has developed chronic RELs).

Acute Exposure Guideline Levels (AEGLs ). AEGLs are developed by the National Advisory Committee (NAC) on Acute Exposure Guideline Levels (NAC/AEGL) f or Hazardous Substances , and then reviewed and published by the National Research Council A s described in the Committee’s “Standing Operating Procedures (SO P) ” ( http://www.epa.gov/opptintr/aegl/pubs/sop.pdf ), AEGLs “represent threshold exposure limits for the general public and are applicable to emergency exposures ranging from 10 min to 8 h.” Their intended application is “for conducting risk assessments to aid in the development of emergency preparedness and prevention plans, as well as real time emergency response actions, for accidental chemical releases at fixed facilities and from transport car riers.” The document states that “the primary purpose of the AEGL program and the NAC/AEGL Committee is to develop guideline levels for once

- in

- a

- lifetime , short

- term exposures to airborne concentrations of acutely toxic, high

- priority chemicals.” In det ailing the intended application of AEGL values, the document states that

, “ It is anticipated that the AEGL values will be used for regulatory and nonregulatory purposes by U.S. Federal and State agencies, and possibly the international community in conjunc tion with chemical emergency response, planning, and prevention programs. More specifically, the AEGL values will be used for conducting various risk assessments to aid in the development of emergency preparedness and prevention plans, as well as real

- tim e emergency response actions, for accidental chemical releases at fixed facilities and from transport carriers.”

The NAC/AEGL defines AEGL

- 1 and AEGL

- 2 as:

“ AEGL

- 1 is the airborne concentration (expressed as ppm or mg/m 3 ) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory effects. However, the effects are not disabling and are transient and reversible upon cessatio n of
exposure. ”

“ AEGL

- 2 is the airborne concentration (expressed as ppm or mg/m 3 ) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long

- lasting adver se health effects or an impaired ability to escape. ”

“ Airborne concentrations below AEGL

- 1 represent exposure levels that can produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptom atic, nonsensory effects. With increasing airborneDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent thres hold levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to unique or idiosyncratic responses, could ex perience the effects described at concentration s below the corresponding AEGL.”

Emergency Response Planning Guidelines (ERPGs). The American Industrial Hygiene Association (AIHA) has developed Emergency Response Planning Guidelines (ERPGs) [ 21 ] for acute exposures at three different levels of severity. These guidelines represent concentrations for exposure of the general population (but not particularly sensitive persons) for up to 1 hour associated with effects expected to be mild or transient (ERPG

- 1), irreversible or serious (ERPG

- 2), and potentially life

- threatening (ERPG

- 3).

ERPG values ( http://www.aiha.org/insideaiha/GuidelineDevelopment/ERPG/Pages/default.as px ) are described in their supporting documentation as follows: “ERPGs are air concentration guidelines for single exposures to agents and are intended for use as tools to assess the adequacy of accident prevention and emergency response plans, including transportation emergency planning, community emergency response plans and incident prevention and mitigation.”

ERPG

- 1 and ERPG

- 2 values are defined by AIHA as follows:

“ ERPG

- 1 is the maximum airborne concentration below which it is believed that nearly all individuals could be exposed for up to 1 hour without experiencing other than mild transient adverse health effects or without perceiving a clearly defined, objectionable odor. ”

“ ERPG

- 2 is the maximum airborne concentration below which it is believed that nearly all individuals could be exposed for up to 1 hour without experiencing or developing irreversible or other serious health effects or symptoms which could impair an individual's ability to take protective action. ”

The emissions inventory for t he Wool Fiberglass Manufacturing and for the Mineral Wool Production source categories includes emissions of 9 HAP with relevant and available quantitative acute dose

- response threshold values. These HAPs, their acute threshold values, and the source of t he value are listed below in Table 2.6

- 2.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Table 2.6

- 2 Dose

- Response Values for Acute Exposure

Pollutant CAS Number AEGL

- 1 (1

- hr) (mg/m 3 ) AEGL

- 2 (1

- hr) (mg/m 3 ) ERPG

- 1 (mg/m 3 ) ERPG

- 2 (mg/m 3 ) REL Dimethyl formamide 6812 2 270 6 30 0 4,4

- Methylene di phenyl diisocyanate 10168 8 5 Propylene oxide 7556 9 170 690 12 0 5 90 3.1 Toluene 108883 750 4500 190 110 0 37 2,4

- Toluene diisocyanate 58484 9 0.14 0.59 0. 071 1.1 Trichloroethylene 79016 700 2400 54 0 27 00 Xylenes (mixed) 1330207 560 4000 22



### 2.7 Risk Characterization

2.7.1 General

The final product of the risk assessment is the risk characterization, in which the information from the previous steps is integrated and an overall conclusion about risk is synthesized that is complete, informative, and useful fo r decision makers. In general, the nature of this risk characterization depends on the information available, the application of the risk information and the resources available. In all cases, major issues associated with determining the nature and exten t of the risk are identified and discussed. Further, the EPA Administrator’s March 1995 Policy for Risk Characterization [ 22 ] specifies that a risk characterization “be prepared in a manner that is clear, transparent, reasonable, and consistent with other risk characterizations of similar scope prepared across programs in the Agency.” These principles of transparency and consistency have been reinforced by the Agency’s Risk Characterization Handbook [ 23 ], in 2002 by the Agency’s information quality guidelin es [ 24 ], and in the OMB/OSTP September 2007 Memorandum on Updated Principles for Risk Analysis 14 , and are incorporated in these assessments.

Estimates of health risk are presented in the context of uncertainties and limitations in the data and methodology. Through our tiered, iterative analytical approach, we have attempted to reduce both uncertainty and bias to the greatest degree possible in these assessments, within the limitations of available time and resources. We provide summaries of risk metrics (i ncluding maximum individual cancer risks and noncancer hazards, as well as cancer incidence estimates) along with a discussion of the major uncertainties associated with their derivation to provide decision makers with the fullest picture of the assessment and its limitations.

14 Memorand um f or t he Heads o f Executive Departments a nd Agencies

- Updated Principles for Risk Analysis ( September 19, 2007 ), From Susan E. Dudley, Administrator, Office of Information and Regulatory Affairs, Office of Management and Budget; and Sharon L. Hays, As sociate Director and Deputy Director for Science, Office of Science and Technology Policy ( http://www.whitehouse.gov/ sites/default/ omb/ assets/omb/ memoranda/fy2007/m07

- 24.pdf )Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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For each carcinogenic HAP included in the assessment that has a potency estimate available, individu al and population cancer risks we re calculated by multiplying the corresponding lifetime average exposure estimate by the appropriate URE. This calculated cancer risk is defined as the upper

- bound probability of developing cancer over a 70

- y r period (i.e., the assumed human lifespan) at that exposure. Because UREs for most HAPs are upper

- bound estimates, actual risks at a given exposu re level may be lower than predicted, and could be

zero.

For EPA’s list of carcinogenic HAPs that act by a mutagenic mode

- of

- action [ 25 ], we applied EPA’s Supplemental Guidance for Assessing Susceptibility from Early

- Life Exposure to Carcinogens [ 26 ]

. This guidance has the effect of adjusting the URE by factors of 10 (for children aged 0

- 1), 3 (for children aged 2

- 15), or 1.6 (for 70 years of exposure beginning at birth), as needed in risk assessments . In this case, this has the effect of increasing the

es timated life time risks for these pollutants by a factor of 1.6. In addition, although only a small fraction of the total POM emissions may be reported as individual compounds, EPA expresses carcinogenic potency for compounds in this group in terms of ben zo[a]pyrene equivalence, based on evidence that carcinogenic POM have the same mutagenic mechanism of action as does benzo[a]pyrene. For this reason

, EPA implem entation policy [ 27 ] recommends applyi ng the Supplemental Guidance to all carcinogenic PAHs for which risk estimates are based on relative potency. Accordingly, we applied the Supplemental Guidance to all unspeciated POM mixtures.

Increased cancer incidence for the entire receptor population within the area of analysis wa s estimated by multiplying the estimated lifetime cancer risk for each census block by the number of people residing in that block, then summing the results for the entire modeled domain. This lifetime population incidence estimate wa s divided by 70 years to obtain an estimate of t he number of cancer cases per year.

In the case of benzene, the high end of the reported cancer URE range was used in our assessments to provide a conservative estimate of potential cancer risks. Use of the high end of the range provides risk estimates t hat are approximately 3.5 times higher than use of the equally plausible low end value. If the estimated benzene

– associated risks exceed 1 in a million, we also evaluate d the impact of using the low end of the URE range on our risk results.

Unlike linear dose

- response assessments for cancer, noncancer health hazards generally are not expressed as a probability of an adverse occurrence. Instead, “risk” for noncancer effects is expressed by comparing an exposure to a reference level as a ratio. The “hazar d quotient” (HQ) is the estimated exposure divided by a reference level (e.g., the RfC). For a given HAP, exposures at or below the reference le vel (HQ≤1) are not likely to cause adverse health effects. As exposures increase above the reference level (HQs increasingly greater than 1), the potential for adverse effects increases. For exposures predicted to be above the RfC, the risk characterizat ion includes the degree of confidence ascribed to the RfC values for the compound(s) of concern (i.e., high, medium, or low confidence) and discusses the impact of this on possible health interpretations.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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The risk characterization for chronic effects oth er than cancer is expressed in terms of the HQ for inhalation, calculated for each HAP at each census block centroid. As discussed above, RfCs incorporate generally conservative uncertainty factors in the face of uncertain extrapolations, such that an HQ greater than one does not necessarily suggest the onset of adverse effects. The HQ cannot be translated to a probability that adverse effects will occur, and is unlikely to be proportional to adverse health effect outcomes in a population

. Screening for potentially significant acute inhalation exposures also followed the HQ approach. We divided the maximum estimated acute exposure by each available short

- term threshold value to develop an array of HQ values relative to the various acute endpoints and thr esholds. In general, when none of these HQ values are greater than one, there is no potential for acute risk. In those cases where HQ values above one are seen, additional information is used to determine if there is a potential for significant acute ris ks.

2.7.2 Mixtures Since most or all receptors in these assessments receive exposures to multiple pollutants rather than a single pollutant, we estimated the aggregate health risks associated with all the exposures from a particular source category combined.

T o combine risks across multiple carcinogens, our assessments use the mixtures guidelines’ [ 28

, 29 ] default assumption of additivity of effects, and combine risks by summing them using the independence formula in the mixtures guidelines.

In assessing noncance r hazard from chronic exposures, in cases where different pollutants cause adverse health effects via completely different modes of action, it may be inappropriate to aggregate HQs. In consideration of these mode

- of

- action differences, the mixtures guidel ines support aggregating effects of different substances in specific and limited ways. To conform to these guidelines, we aggregated non

- cancer HQs of HAPs that act by similar toxic modes of action, or (where this information is absent) that affect the sa me target organ. This process creates, for each target organ, a target

- organ

- specific hazard index (TOSHI), defined as the sum of hazard quotients for individual HAPs that affect the same organ or organ system. A ll TOSHI calculations presented here were based exclusively on effects occurring at the “ critical dose” (i.e., the lowest dose that produces adverse health effects). Although HQs associated with some pollutants have been aggregated into more than one TOSHI, this has been done only in cases where the critical dose affects more than one target
organ . Because impacts on organs or systems that occur above the critical dose have not been included in the TOSHI calculations, some TOSHIs may have been underestimated. As with the HQ, the TOSHI should not be interpreted as a probability of adverse effects, or as strict delineation of “safe” and “unsafe” levels. Rather, the TOSHI is another measure of the potential for adverse health outcomes associated with pollutant exposure, and needs to be interpreted carefully by health scientists and risk managers.

Because of the conservative nature of the acute inhalation screening and the variable nature of emissions and potential exposures, acute impacts were screened on an individual pollutantDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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basis, not using th e TOSHI approach.



### 3 Risk Results

3.1 Source Category Description and Results

The FPUF Production MACT standards apply to each new and existing flexible polyurethane foam or rebond foam process that produces flexible polyurethane foam or rebond foam, emits HAP , and is located at a contiguous, major source plant site. There are three types of FPUF producers in the source category: slabstock, molded and rebond. Slabstock foam is produced in large continuous buns that are then cut into the desired size and shape. Slabstock foam products are primarily used in furniture seat cushions and bedding materials. Molded foam is produced by "shooting" the foam mixture into a mold of the desired shape and size. Molded foam is typically used in automotive seats, packaging and a range of specialty products. Rebond foam is made from scrap foam that is converted into a material primarily used for carpet underlay. Rebond foam production is often co

- located with slabstock foam production facilities.

T here are 13 FPUF production fa cilities subject to the MACT standards: 7 slabstock, 6 molded and 2 rebond. One rebond facility is co

- located with a slabstock facility, and the other rebond facility is co

- located with a molded foam facility.

Table 3.1

- 1 summarizes the emissions for the Flexible Polyurethane Foam Production source category. Based on the se data, the HAP emitted in largest quantities in total from these facilities are 2,4

- toluene diisocyante, propylene oxide, and toluene ; emissions of these 3 pollutants account for 93 perc ent of the total HAP emissions by mass from the data set. No PB HAP emissions are reported in the data set for the source category.

The HAP emission points at FPUF production facilities depend on the type of foam being produced. HAP emission s point s f or slabstock foam facilities include the foam production line, storage vessels

, and equipment leaks. At molded and rebond foam facilities, the primary HAP emission points are storage vessels and equipment leaks.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Table 3.1

- 1 Summary of Emissions from t he Flexible Polyurethane Foam Production Category and Availability of Dose

- Response Values

HAP Emissions (tpy) Number of Facilities Reporting

HAP (7 facilities in data

set) Prioritized Inhalation Dose

- Response Value Identified by OAQPS a

PB

HAP? Unit Risk Estimate for

Cancer? Reference Concentration for Noncancer? Health Benchmark Values for Acute Noncancer? 2,4

- toluene Diisocyanate 0.6 9    Propylene Oxide 0.2 1    Toluene 0.08 1   Methyl Isobutyl Ketone 0.03 1  Methylene Diphenyl Diisocyanate 0.02 7   Xylenes (mixed) 0.01 1   Trichloroethylene 0.01 1    Diethanolamine 0.0004 1  Dimeth yl Formamide 0.0001 1  

a Tables 2.6

- 1 (a) and (b) of this report contain the URE and RfC values for the HAP emitted from Flexible Polyurethane Foam P roduction facilities. Table 2.6

- 2 of this report contains the acute noncancer values for the HAP emitted from Flexible Polyurethane Foam P roduction facil ities. Specific dose

- response values for each chemical are identified on EPA’s Technology Transfer Network website for air toxics at http ://www.epa.gov/ttn/atw/toxsource/summary.html

.



### 3.2 Risk Characterization

This section presents the results of the risk assessment for the Flexible Polyurethane Foam Production source category. The basic chronic inhalation risk estimates presented here ar e the maximum individual lifetime cancer risk, the maximum chronic hazard index, and the cancer incidence. We also present results from our acute inhalation impact screening in the form of maximum hazard quotients, as well as the results of our preliminar y screen for potential non

inhalation risks from PB HAP , as applicable. Also presented are the HAP “drivers,” which are the HAP that collectively contribute 90 percent of the maximum cancer risk or maximum hazard index at the highest exposure location

.

T able s 3 .2

- 1 and 3.2

- 2 summarize the chronic and acute inhalation risk results for this source category. The results for the Flexible Polyurethane Foam Production source category indicate that maximum lifetime individual cancer risks could be up to 0.7 in a million , based on actual emissions . The major contributor to th is risk is 2,4

- Toluene diisocyanate

. There were no cancer risks above 1 in a million based on actual emissions . The maximum chronic non

cancer TOSHI value for the source category could be up to 0. 9 with emissions of 2,4

- toluene diisocyanate dominating t hose impacts, indicating no sig nificant potential for chronic noncancer impacts.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Worst

- case screening a cute hazard quotients (HQs) were calculated for every HAP shown in Table 3.1

- 1 that h as an acute benchmark, and the high est acute HQ ( ERPG

- 1 of 0.9 for 2,4

- toluen diisocyanate ) is shown in Table 3 .2

- 1

. The default emissions multiplier of 10 was used to estimate the peak hourly emission rates from the average rates

. There were no faciliti es with an acute HQ above 1.

Chronic noncancer target organ specific hazard indices (HIs) were calculated for every HAP shown in Table 3.1

- 1 that has a chronic benchmark, and the highest target organ specific HI ( 0. 9 for 2,4

- toluene diisocyanate ) is s hown in Table 3.2

- 1. There were no HIs greater than 1 for this source category.

We conducted a screening

- level evaluation of the potential human health risks associated with emissions of PB HAP. There were no r eported emissions of PB HAP from facili ties in the source category

. 15

In order to estimate the risk from each type of emission point (e.g., slabstock tanks ), each emission point was assigned to an emission point type. Table 3.2

- 3 presents the maximum individual lifetime cancer risk, populati on exposure, and incidence from each modeled emission point type.

We determined that MACT

- allowable HAP ABA emissions levels at slabstock production facilities are greater than actual HAP ABA emissions, while allowable emissions from all other processes a re equal to actual emissions. The inhalation risk modeling using MACT

allowable HAP ABA emissions and the actual emissions for the other processes at slabstock production facilities, indicate that the maximum lifetime individual cancer risk could be up to 5

- in

- 1 million, the maximum chronic non

- cancer TOSHI value could be up to 0.9, and the maximum off

- facility site acute HQ value could be up to 4, based on the REL value for methylene chloride. The total estimated national cancer incidence from these facili ties based on the MACT

- allowable emission levels is 0.0004 excess cancer cases per year or one case in every 2,500 years.

The facility

- wide MIR and TOSHI are based on actual emissions from all emissions sources at the identified facilities. The results in dicate that 3 facilities have a facility

- wide cancer MIR greater than or equal to 1

- in

- 1 million. The maximum facility

- wide MIR is 20

- in

- 1 million, with the FPUF production source category contributing less than 10 percent of the risk. The maximum facility

- wide TOSHI is 0.9, with the FPUF production source category contributing 100 percent to the facility

- wide TOSHI.

15 ICF International. TRIM

- Based Multipathway Screening Scenario . Prepared for U.S. Environmental Protection Agency, Research Triangle Park, NC. October 2008.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Table 3.2

- 1 Summary of Source Category Level Inhalation Risks for Flexible Polyurethane Foam Production

Result HAP “Drivers” Facilitie s in Source Category Number of Facilities Estimated to be in Source Category 13 n/a Number of Facilities Identified in the NEI and Modeled in Preliminary Risk Assessment 13 n/a

Cancer Risks
Maximum Individual Lifetime Cancer Risk (in 1 million) 0.7 2,4

- toluene diisocyanate Number of Facilities with Maximum Individual Lifetime Cancer Risk: Greater than or equal to 100 in 1 million 0 n/a Greater than or equal to 10 in 1 million 0 n/a Greater than or equal to 1 in 1 million 0 n/a Chronic Noncancer Risks

Maximum Hazard Index 0. 9 2,4

- toluene diisocyanate Num ber of Facilities with Maximum Respiratory Hazard Index: Greater than 1 0 n/a Refined Acute Noncancer Screening Results

Maximum Acute Hazard Quotient [using scali ng factor of 10 ] 0.9 2,4

- t oluene diisocyanate

( ERPG

- 1) Number of Facilities With Potential for Acute Effects 0 n/a Population Exposure Number of People Living Within 50 Kilometers of Facilities Modeled 10,400,000 n/a Number of People Exposed to Cancer Risk: Greater than or eq ual to 100 in 1 million 0 n/a Greater than or equal to 10 in 1 million 0 n/a Greater than or equal to 1 in 1 million 0 n/a Number of People Exposed to Noncancer Respiratory Hazard Index: Greater than 1 0 n/a Estimated Cancer Incidence (excess cance r cases per year) 0.000 04 n/a Contribution of HAP to Cancer Incidence: 2,4

- toluene diisocyanate Propylene oxide Trichloroethylene 94 % 4 % 2% n/aDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Table 3.2

- 2 Summary of Refined Acute Results for Flexible Polyurethane Foam Productio n Facilities

Refined Results MAXIMUM ACUTE HAZARD QUOTIENTS ACUTE DOSE

- RESPONSE VALUES

Based

on REL Based on AEGL

- 1/ ERPG

- 1 Based on AEGL

- 2/ ERPG

- 2 REL (mg/m 3 ) AEGL

- 1 (1

- hr) (mg/m 3 ) ERPG

- 1 (mg/m 3 ) AEGL

- 2 (1

- hr)(mg/m 3 ) ERPG

- 2 (mg/m 3 ) HAP Max. 1

- hr. Air Conc. (mg/m 3 )
2,4

- toluene diisocyanate 0.06

- 0.4/0.9 0.1/0.06

- 0.14 0.071 0.59 1.1

Notes on Refined Process: 1) The screening was performed for all emitted HAP with available acute dose

- response values. Only those pollutants whose screening H Qs were greater than 1 for at least one acute threshold value are shown in the table. 2) HAP with available acute dose

- response values which are not in the table do not carry any potential for posing acute health risks, based on an analysis of currently avail able emissions data. Notes on Acute Dose

- Response Values: REL

– California EPA reference exposure level for no adverse effects. Most, but not all, RELs are for 1

- hour exposures. AEGL

– Acute exposure guideline levels represent emergency exposure (1

- hou r) limits for the general public. AEGL

- 1 is the exposure level above which it is predicted that the general population, including susceptible individuals, could experience effects t hat are notable discomfort, but which are transient and reversible upon ces sation of exposure. AEGL

- 2 is the exposure level above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long

- lasting adverse health effects of an impaired ability to escap e. E R P G

– Emergency Removal Program guidelines represent emergency exposure (1

- hour) limits for the general public. ERPG

- 1 is the maximum level below which it is believed that nearly all individuals could be exposed for up to 1 hour without experiencing o ther than mild, transient adverse health effects. ERPG

- 2 is the maximum exposure below which it is believed that nearly all individuals could be exposed for up to 1 hour without experiencing or developing irreversible or other serious health effects or sym ptoms which could impair an individual’s ability to take protective action.

Table 3.2

- 3 . Cancer Risk Estimates by Emission Point Type for the Flexible Polyurethane Foam Production Source Category

Maximum Overall Slabstock Process Emissions Slabstock Ta nks Molded Foam Emissions Cancer Risk due to Emission Point Type: Maximum (in 1 million) 0.7 0.7 0.05 0.004 Population Exposure due to Emission Point Type:

>= 100 in 1 million 0 0 0 0

>= 10 in 1 million 0 0 0 0

>= 1 in 1 million 0 0 0 0

Incidence du e to Emission Point Type: 0.00004 0.00003 0.000001 0.0000008

Sm Slabstock Process Emissions Sm Slabstock Tanks

Cancer Risk due to Emission Point Type: Maximum (in 1 million) 0.0005 0.0001 Population Exposure due to Emission Point Type:

>= 100 i n 1 million 0 0

>= 10 in 1 million 0 0

>= 1 in 1 million 0 0

Incidence due to Emission Point Type: 0.0000002 0.000000006Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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### 4 General Discussion of Uncertainties and How They Have Been Addressed

4.1 Exposure Modeling Uncertainties

Although every effort h as been made to identify all the relevant facilities and emission points, as well as to develop accurate estimates of the annual emission rates for all relevant HAP, the uncertainties in our emission inventory likely dominate the uncertainties in our expos ure modeling estimates. The chronic ambient modeling uncertainties are considered relatively small in comparison, since we are using EPA’s refined local dispersion model with site

specific parameters and reasonably representative meteorology. If anything , the population exposure estimates are biased high by not accounting for short

- or long

- term population mobility, and by neglecting processes like deposition, plume depletion, and atmospheric degradation. Additionally, estimates of the maximum individual risk (MIR) contain uncertainty , because they are deriv ed at census block centroid locations rather than actual residences. This uncertainty is known to create potential underestimates and overestimates of the actual MIR values for individual facilities, but, overall, it is not thought to have a significant impact on the estimated MIR for a source category. Finally, we did not factor in the possibility of a source closure occurring during the 70

- year chronic exposure period, leading to a potential upward bias in both the MIR and population risk estimates; nor did we factor in the possibility of population growth during the 70

- year chronic exposure period, leading to a potential downward bias in both the MIR and population risk estimates.

A sensitivity ana lysis performed for the 1999 NATA found that the selection of the meteorology dataset location could result in a range of chronic ambient concentrations which varied from as much as 17% below the predicted value to as much as 84% higher than the predicted value. This variability translates directly to the predicted exposures and risks in our assessment, indicating that the actual risks could vary from 17% lower to 84% higher than the predicted values.

We have purposely biased the acute screening results h igh, considering that they depend upon the joint occurrence of independent factors, such as hourly emissions rates, meteorology and human activity patterns. Furthermore, in cases where multiple acute threshold values are considered scientifically acceptab le we have chosen the most conservative of these threshold values , erring on the side of overestimating potential health risks from acute exposures. In the cases where these results indicated the potential for exceeding short

- term health thresholds, we ha ve refined our assessment by developing a better understanding of the geography of the facility relative to potential exposure locations.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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### 4.2 Uncertainties in the Dose

- Response Relationships

In the sections that follow, separate discussions are provide d on uncertainty associated with cancer potency factors and for noncancer reference values. Cancer potency values are derived for chronic (lifetime) exposures. Noncancer reference values are generally derived for chronic exposures (up to a lifetime), bu t may also be derived for acute ( <24 hours), short

- term (>24 hours up to 30 days), and subchronic (>30 days up to 10% of lifetime) exposure durations, all of which are derived based on an assumption of continuous exposure throughout the duration specified. For the purposes of assessing all potential health risks associated wit h the emissions included in an assessment, we rely on both chronic (cancer and noncancer) and acute ( noncancer ) benchmarks, which are described in more detail below.

Although every effort is made to identify peer

- review ed dose

- response values for all HAPs emitted by the source category included in an assessment, some HAP have no peer

- reviewed cancer potency values or reference values for chronic non

- cancer or acute effects (inhalation or ingestion) . Since exposure s to these pollutants cannot be included in a quantitative risk estimate, an understatement of risk for these pollutants at environmental exposure levels is possible.

Additionally, chronic dose

- response values for certain compounds included in the assessm ent may be under EPA IRIS review and revised assessments may determine that these pollutants are more or less potent than currently thought. We will re

- evaluate risks if, as a result of these reviews, a dose

- response metric changes enough to indicate that the risk assessment may significantly mischaracterize human health risk

Cancer assessment

The discussion of dose

- response uncertainties in the estimation of cancer risk below focuses on the uncertainties associated with the specific approach currently u sed by the EPA to develop cancer potency factors. In general, these same uncertainties attend the development of cancer potency factors by CalEPA, the source of peer

- reviewed cancer potency factors used where EPA

- developed values are not yet available. T o place this discussion in context, we provide a quote from the EPA’s Guidelines for Carcinogen Risk Assessment [ 30 ] (herein referred to as Cancer Guidelines ). “The primary goal of EPA actions is protection of human health; accordingly, as an Agency policy , risk assessment procedures, including default options that are used in the absence of scientific data to the contrary, should be health protective.” The approach adopted in this document is consistent with this approach as described in the Cancer Guidel ines

. For cancer endpoints EPA usually derives an oral slope factor for ingestion and a unit risk value for inhalation exposures. These values allow estimation of a lifetime probability of developing cancer given long

- term exposures to the pollutant. De pending on the pollutant being evaluated, EPA relies on both animal bioassay and epidemiological studies to characterize cancer risk. As a science policy approach, consistent with the CancerDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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Guidelines , EPA uses animal cancer bioassays as indicators of po tential human health risk when other human cancer risk data are unavailable.

Extrapolation of study data to estimate potential risks to human populations is based upon EPA’s assessment of the scientific database for a pollutant using EPA’s guidance doc uments and other peer

- reviewed methodologies. The EPA Cancer Guidelines describes the Agency’s recommendations for methodologies for cancer risk assessment. EPA believes that cancer risk estimates developed following the procedures described in the Cance r Guidelines and outlined below generally provide an upper bound estimate of risk. That is, EPA’s upper bound estimates represent a “plausible upper limit to the true value of a quantity” (although this is usually not a true statistical confidence limit). 16 In some circumstances, the true risk could be as low as zero; however, in other circumstances the risk could also be greater. 17 When developing an upper bound estimate of risk and to provide risk values that do not underestimate risk, EPA generally re lies on conservative default approaches. 18 EPA also uses the upper bound (rather than lower bound or central) estimates in its assessments, although it is noted that this approach can have limitations for some uses (e.g. priority setting, expected benefit s analysis).

Such health risk assessments have associated uncertainties, some which may be considered quantitatively, and others which generally are expressed qualitatively. Uncertainties may vary substantially among cancer risk assessments associated wi th exposures to different pollutants, since the assessments employ different databases with different strengths and limitations and the procedures employed may differ in how well they represent actual biological processes for the assessed substance. EPA’s Risk Characterization Handbook also recommends that risk characterizations present estimates demonstrating the impact on the assessment of alternative choices, data, models and assumptions [ 31 ]. Some of the major sources of uncertainty and variability in deriving cancer risk values are described more fully below.

(1) The qualitative similarities or differences between tumor responses observed in experimental animal bioassays and those which would occur in humans is a source of uncertainty in cancer risk assessment. In general, EPA does not assume that tumor sites observed in an experimental animal bioassay are necessarily predictive of the sites at which

16 IRIS glossary (www.epa.gov/NCEA/iris/help_gloss.htm).
17 The exception to this is the URE for benzene, which is considered to cover a range of values, each end of which is co nsidered to be equally plausible, and which is based on maximum likelihood estimates.
18 According to the NRC report Science and Judgment in Risk Assessment (NRC, 1994) “[Default] options are generic approaches, based on general scientific knowledge and pol icy judgment, that are applied to various elements of the risk

- assessment process when the correct scientific model is unknown or uncertain.” The 1983 NRC report Risk Assessment in the Federal Government: Managing the Process defined default option as “th e option chosen on the basis of risk assessment policy that appears to be the best choice in the absence of data to the contrary” (NRC, 1983a, p. 63). Therefore, default options are not rules that bind the agency; rather, the agency may depart from them i n evaluating the risks posed by a specific substance when it believes this to be appropriate. In keeping with EPA’s goal of protecting public health and the environment, default assumptions are used to ensure that risk to chemicals is not underestimated ( although defaults are not intended to overtly overestimate risk). See EPA 2004 An Examination of EPA Risk Assessment Principles and Practices, EPA/100/B

- 04/001 available at: http://www.epa.gov/osa/pdfs/ratf

- final.pdf.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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tumors would occur in humans. 19 However, unless scientific support is available to show otherwise, EPA assumes that tumors in animals are relevant in humans, regardless of target organ concordance. For a specific pollutant, qualitative differences in species responses can lead to either under

- estimation or over

- estimation of human cancer risks.

(2) Uncertainties regarding the most appropriate dose metric for an assessment can also lead to differences in risk predictions. For example, the measure of dose is commonly expressed in units of mg/kg/d ingested or the inhaled concentration of the pollutant. However, data may support development of a pharmacokinetic model for the absorption, distribution, metabolism and excretion of an agent, which may result in improved dose metrics (e.g., average blood concentration of the pollutant or the quantity of agen t metabolized in the body). Quantitative uncertainties result when the appropriate choice of a dose metric is uncertain or when dose metric estimates are themselves uncertain (e.g., as can occur when alternative pharmacokinetic models are available for a compound). Uncertainty in dose estimates may lead to either over or underestimation of risk.

(3) For the quantitative extrapolation of cancer risk estimates from experimental animals to humans, EPA uses scaling methodologies (relating expected response t o differences in physical size of the species), which introduce another source of uncertainty. These methodologies are based on both biological data on differences in rates of process according to species size and empirical comparisons of toxicity between experimental animals and humans. For a particular pollutant, the quantitative difference in cancer potency between experimental animals and humans may be either greater than or less than that estimated by baseline scientific scaling predictions due to un certainties associated with limitations in the test data and the correctness of scaled estimates.

(4) EPA cancer risk estimates, whether based on epidemiological or experimental animal data, are generally developed using a benchmark dose (BMD) analysis to estimate a dose at which there is a specified excess risk of cancer, which is used as the point of departure (or POD) for the remainder of the calculation. Statistical uncertainty in developing a POD using a benchmark dose (BMD) approach is generally addressed though use of the 95% lower confidence limit on the dose at which the specified excess risk occurs (the BMDL), decreasing the likelihood of understating risk. EPA has generally utilized the multistage model for estimation of the BMDL using cance r bioassay data (see further discussion below).

(5) Extrapolation from high to low doses is an important, and potentially large, source of uncertainty in cancer risk assessment. EPA uses different approaches to low dose risk assessment (i.e., developing estimates of risk for exposures to environmental doses of an agent from observations in experimental or epidemiological studies at higher dose) depending on the available data and understanding of a pollutant’s mode of action (i.e., the manner in which a p ollutant causes cancer). EPA’s Cancer Guidelines express a preference for the use of reliable, compound

- specific, biologically

- based risk models when feasible; however, such models are rarely available. The mode of action for a pollutant (i.e., the manne r in which a

19 Per the EPA Cancer Guidelines: “The default option is that positive effects in animal cancer studies indicate that the agent under study can have carcinogenic potential in humans.” and “Target organ concordance is not a prerequisite for evaluating the implications of animal study results fo r humans.”Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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pollutant causes cancer) is a key consideration in determining how risks should be estimated for low

- dose exposure. A reference value is calculated when the available mode of action data show the response to be nonlinear (e.g., as in a thresh old response). A linear low

- dose (straight line from POD) approach is used when available mode of action data support a linear (e.g., nonthreshold response) or as the most common default approach when a compound’s mode of action is unknown. Linear extrap olation can be supported by both pollutant

- specific data and broader scientific considerations. For example, EPA’s Cancer Guidelines generally consider a linear dose

- response to be appropriate for pollutants that interact with DNA and induce mutations. P ollutants whose effects are additive to background biological processes in cancer development can also be predicted to have low

- dose linear responses, although the slope of this relationship may not be the same as the slope estimated by the straight line

a pproach.

EPA most frequently utilizes a linear low

- dose extrapolation approach as a baseline science

policy choice (a “default”) when available data do not allow a compound

- specific determination. This approach is designed to not underestimate risk in the face of uncertainty and variability. EPA believes that linear dose

- response models, when appropriately applied as part of EPA’s cancer risk assessment process, provide an upper bound estimate of risk and generally provide a health protective approach. Note that another source of uncertainty is the characterization of low

- dose nonlinear, non

- threshold relationships. The National Academy of Sciences has encouraged the exploration of sigmoidal type functions (e.g., log

- probit models) in representing dos e response relationships due to the variability in response within human populations. Another National Research Council (NRC) report [ 32 ] suggests that models based on distributions of individual thresholds are likely to lead to sigmoidal

- shaped dose

- respo nse functions for a population. This report notes sources of variability in the human population: “One might expect these individual tolerances to vary extensively in humans depending on genetics, coincident exposures, nutritional status, and various oth er susceptibility factors...” Thus, if a distribution of thresholds approach is considered for a carcinogen risk assessment, application would depend on ability of modeling to reflect the degree of variability in response in human populations (as opposed to responses in bioassays with genetically more uniform rodents). Note also that low dose linearity in risk can arise for reasons separate from population variability: due to the nature of a mode of action and additivity of a chemical’s effect on top of background chemical exposures and biological
processes.

As noted above, EPA’s current approach to cancer risk assessment typically utilizes a straight line approach from the BMDL. This is equivalent to using an upper confidence limit on the slope of the straight line extrapolation. The impact of the choice of the BMDL on bottom line risk estimates can be quantified by comparing risk estimates using the BMDL value to central estimate BMD values, although these differences are generally not a large contrib utor to uncertainty in risk assessment (Subramaniam et. al., 2006) [ 33 ]. It is important to note that earlier EPA assessments, including the majority of those for which risk values exist today, were generally developed using the multistage model to extrapo late down to environmental dose levels and did not involve the use of a POD. Subramaniam et. al. (2006) also provide comparisons indicating that slopes based on straight line extrapolation from a POD do notDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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show large differences from those based on the u pper confidence limit of the multistage model.

(6) Cancer risk estimates do not generally make specific adjustments to reflect the variability in response within the human population

— resulting in another source of uncertainty in assessments. In the div erse human population, some individuals are likely to be more sensitive to the action of a carcinogen than the typical individual, although compound

- specific data to evaluate this variability are generally not available. There may also be important life

s tage differences in the quantitative potency of carcinogens and, with the exception of the recommendations in EPA’s Supplemental Cancer Guidance for carcinogens with a mutagenic mode of action, risk assessments do not generally quantitatively address life stage differences. However, one approach used commonly in EPA assessments that may help address variability in response is to extrapolate human response from results observed in the most sensitive species and sex tested, resulting typically in the highest URE which can be supported by reliable data, thus supporting estimates that are designed not to underestimate risk in the face of uncertainty and variability.

Chronic noncancer assessment

Chronic noncancer reference values represent chronic exposure lev els that are intended to be health

- protective. That is, EPA and other organizations which develop noncancer reference values (e.g., the Agency for Toxic Substances and Disease Registry

– ATSDR) utilize an approach that is intended not to underestimate risk in the face of uncertainty and variability. When there are gaps in the available information, uncertainty factors (UFs) are applied to derive reference values that are intended to be protective against appreciable risk of deleterious effects . Uncertaint y factors are commonly default values 20 e.g., factors of 10 or 3, used in the absence of compound

- specific data; where data are available, uncertainty factors may also be developed using compound

- specific information. When data are limited, more assumption s are needed and more default factors are used. Thus there may be a greater tendency to overestimate risk

— in the sense that further study might support development of reference values that are higher (i.e., less potent) because fewer default assumptions a re needed. However, for some pollutants it is possible that risks may be underestimated.

For non

- cancer endpoints related to chronic exposures, EPA derives a Reference Dose (RfD) for exposures via ingestion, and a Reference Concentration (RfC) for inhala tion exposures.

20 According to the NRC report Science and Judgment in Risk Assessment (NRC, 1994) “[Default] options are generic approaches, based on general scientific knowledge and policy judgment, that are applied to various elements of the risk

- assessment process when the correct scientific model is unknown or uncertain.” The 1983 NRC report Risk Assessment in the Federal Government: Managing the Process defined default option as “the option chosen on the basis of risk assessment policy that appears to be the best choice in the absence of data to the contrary” (NRC, 1983a, p. 63). Therefore, default options are not rules that bind the agency; rather, the agency may depart from them in evaluating the risks posed by a specific substance when it believes this to be appropriate. In keeping with EPA’s goal of protecting public health and the environment, default assumptions are used to ensure that risk to chemicals is not underestimated (although defaults are not intended to overtly overestimate risk). See EPA 2 004 An examination of EPA Risk Assessment Principles and Practices, EPA/100/B

- 04/001 available at: http://www.epa.gov/osa/pdfs/ratf

- final.pdf.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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These values provide an estimate (with uncertainty spanning perhaps an order of magnitude) of daily oral exposure (RfD) or of a continuous inhalation exposure (RfC) to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. 21 To derive values that are intended to be “without appreciable risk,” EPA’s methodology relies upon an uncertainty factor (UF) approach [ 34 ],[ 35 ] which includes consideration of both uncertainty and variability.

EPA begins by evaluating all of the available peer

- reviewed literature to determine non

cancer endpoints of concern, evaluating the quality, strengths and limitations of the available studies. EPA typically chooses the rel evant endpoint that occurs at the lowest dose, often using statistical modeling of the available data, and then determines the appropriate point of departure (POD) for derivation of the reference value. A POD is determined by (in order of preference): (1) a statistical estimation using the benchmark dose (BMD) approach; (2) use of the dose or concentration at which the toxic response was not significantly elevated (no observed adverse effect level

— NOAEL); or (3) use of the lowest observed adverse effect l evel (LOAEL).

A series of downward adjustments using default UFs is then applied to the POD to estimate the reference value [ 36 ] . While collectively termed “UFs”, these factors account for a number of different quantitative considerations when utilizing observed animal (usually rodent) or human toxicity data in a risk assessment. The UFs are intended to account for: (1) variation in susceptibility among the members of the human population (i.e., inter

- individual variability); (2) uncertainty in extrapola ting from experimental animal data to humans (i.e., interspecies differences); (3) uncertainty in extrapolating from data obtained in a study with less

- than

- lifetime exposure (i.e., extrapolating from subchronic to chronic exposure); (4) uncertainty in ext rapolating from a LOAEL in the absence of a NOAEL; and (5) uncertainty when the database is incomplete or there are problems with applicability of available studies

. When scientifically sound, peer

- reviewed assessment

- specific data are not available, defa ult adjustment values are selected for the individual UFs. For each type of uncertainty (when relevant to the assessment) , EPA typically applies an UF value of 10 or 3 with the cumulative UF value leading to a downward adjustment of 10

- 3000 fold from the selected POD. An UF of 3 is used when the data do not support the use of a 10

- fold factor. If an extrapolation step or adjustment is not relevant to an assessment (e.g., if applying human toxicity data and an interspecies extrapolation is not required) t he associated UF is not used. The major adjustment steps are described more fully below.

1) Heterogeneity among humans is a key source of variability as well as uncertainty. Uncertainty related to human variation is considered in extrapolating doses fr om a subset or smaller

- sized population, often of one sex or of a narrow range of life stages (typical of occupational epidemiologic studies), to a larger, more diverse population. In the absence of pollutant

- specific data on human variation, a 10

- fold UF is used to account for uncertainty associated with human variation. Human variation may be larger or smaller; however, data to examine the potential magnitude of human variability are often unavailable. In some situations, a smaller UF of 3 may be appli ed to reflect a known lack of significant variability among humans.

21 See IRIS glossaryDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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2) Extrapolation from results of studies in experimental animals to humans is a necessary step for the majority of chemical risk assessments . When interpreting animal data, the concentr ation at the POD (e.g. NOAEL, BMDL) in an animal model (e.g. rodents) is extrapolated to estimate the human response. While there is long

- standing scientific support for the use of animal studies as indicators of potential toxicity to humans , there are

un certainties in such extrapolations. In the absence of data to the contrary, the typical approach is to use the most relevant endpoint from the most sensitive species and the most sensitive sex in assessing risks to the average human. Typically

, compound specific data to evaluate relative sensitivity in humans versus rodents are lacking, thus leading to uncertainty in this extrapolation. Size

- related differences (allometric relationships) indicate that typically humans are more sensitive than rodents when compared on a mg/kg/day basis. The default choice of 10 for the interspecies UF is consistent with these differences. For a s pecific chemical, differences in species responses may be greater or less than this value

.

Pharmacokinetic models are useful to examine species differences in pharmacokinetic processing and associated uncertainties; however, such dosimetric adjustments are not always possible. Information may not be available to quantitatively assess toxicokinetic or toxicodynamic differences bet ween animals and humans, and in many cases a 10

- fold UF (with separate factors of 3 for toxicokinetic and toxicodynamic components) is used to account for expected species differences and associated uncertainty in extrapolating from laboratory animals to h umans in the derivation of a reference value. If information on one or the other of these components is available and accounted for in the cross

- species extrapolation, a UF of 3 may be used for the remaining component.

3) In the case of reference values for chronic exposures where only data from shorter durations are available (e.g., 90

- day subchronic studies in rodents) or when such data are judged more appropriate for development of an RfC, an additional UF of 3 or 10

- fold is typically applied unless t he available scientific information supports use of a different value.

4) Toxicity data are typically limited as to the dose or exposure levels that have been tested in individual studies; in an animal study, for example, treatment groups may differ in

ex posure by up to an order of magnitude. The preferred approach to arrive at a POD is to use BMD analysis; however, this approach requires adequate quantitative results for a meaningful analysis, which is not always possible. Use of a NOAEL is the next pre ferred approach after BMD analysis in determining a POD for deriving a health effect reference value. However, many studies lack a dose or exposure level at which an adverse effect is not observed (i.e., a NOAEL is not identified). When using data limite d to a LOAEL, a UF of 10 or 3

- fold is often applied.

5) The database UF is intended to account for the potential for deriving an underprotective RfD/RfC due to a data gap preventing complete characterization of the chemical’s toxicity. In the absence of studies for a known or suspected endpoint of concern, a UF of 10 or 3

- fold is typically applied. There is no RfD or other comparable chronic health benchmark value for lead compounds. Thus, to address multipathway human health and environmental risks ass ociated withDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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emissions of lead from these facilities, ambient lead concentrations were compared to the NAAQS for lead. In developing the NAAQS for lead, EPA considered human health evidence reporting adverse health effects associated with lead exposure, a s well as an EPA conducted multipathway risk assessment that applied models to estimate human exposures to air

- related lead and the associated risk (73FR at 66979). EPA also explicitly considered the uncertainties associated with both the human health evid ence and the exposure and risk analyses when developing the NAAQS for lead. For example, EPA considered uncertainties in the relationship between ambient air lead and blood lead levels (73FR at 66974), as well as uncertainties between blood lead levels an d loss of IQ points in children (73FR at 66981). In considering the evidence and risk analyses and their associated uncertainties, the EPA Administrator noted his view that there is no evidence

- or risk

- based bright line that indicates a single appropriat e level. Instead, he noted, there is a collection of scientific evidence and judgments and other information, including information about the uncertainties inherent in many relevant factors, which needs to be considered together in making this public healt h policy judgment and in selecting a standard level from a range of reasonable values (73FR at 66998). In so doing, the Administrator decided that, a level for the primary lead standard of 0.15 μg/m 3 , in combination with the specified choice of indicator, averaging time, and form, is requisite to protect public health, including the health of sensitive groups, with an adequate margin of safety (73FR at 67006). A thorough discussion of the health evidence, risk and exposure analyses, and their associated uncertainties can be found in EPA’s final rule revising the lead NAAQS (73 FR 66970

- 66981, November 12, 2008).

We also note the uncertainties associated with the health

- based (i.e., primary) NAAQS are likely less than the uncertainties associated with dose

- response values developed for many of the other HAP, particularly those HAP for which no human health data exist. In 1988, EPA’s IRIS program reviewed the health effects data regarding lead and its inorganic compounds and determined that it would be inappropriate to develop an RfD for these compounds, saying, “A great deal of information on the health effects of lead has been obtained through decades of medi cal observation and scientific research. This information has been assessed in the development of air and water quality criteria by the Agency's Office of Health and Environmental Assessment (OHEA) in support of regulatory decision

- making by the Office of Air Quality Planning and Standards (OAQPS) and by the Office of Drinking Water (ODW). By comparison to most other environmental toxicants, the degree of uncertainty about the health effects of lead is quite low. It appears that some of these effects, par ticularly changes in the levels of certain blood enzymes and in aspects of children's neurobehavioral development, may occur at blood lead levels so low as to be essentially without a threshold. The Agency's RfD Work Group discussed inorganic lead (and lea d compounds) at two meetings (07/08/1985 and 07/22/1985) and considered it inappropriate to develop an RfD for inorganic lead.” EPA’s IRIS assessment for Lead and compounds (inorganic) (CASRN 7439

- 92

- 1), http://www.epa.gov/iris/subst/0277.htm

.

We note further that because of the multi

- pathway, multi

- media impacts of lead, the risk assessment supporting the NAAQS considered direct inhalation exposures and indirect air

related multi

- pathway exposures fro m industrial sources like primary and secondary lead smelting operations. It also considered background lead exposures from other sources (like contaminated drinking water and exposure to lead

- based paints). In revising the NAAQS forDraft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

– FOR PUBLIC COMMENT, DO NOT CITE OR QUOTE 37

lead, we note that t he Administrator placed more weight on the evidence

- based framework and less weight on the results from the risk assessment, although he did find the risk estimates to be roughly consistent with and generally supportive of the evidence

- based framework appl ied in the NAAQS determination (73FR at 67004). Thus, when revising the NAAQS for lead to protect public health with an adequate margin of safety, EPA considered both the evidence

- based framework and the risk assessment, albeit to different extents.

Acute noncancer assessment

Many of the UFs used to account for variability and uncertainty in the development of acute reference values are quite similar to those developed for chronic durations, but more often using individual UF values that may be less than 10. UFs are applied based on chemical

specific or health effect

- specific information (e.g., simple irritation effects do not vary appreciably between human individuals, hence a value of 3 is typically used), or based on the purpose for the reference value (see the following paragraph). The UFs applied in acute reference value derivation include: 1) heterogeneity among humans; 2) uncertainty in extrapolating from animals to humans; 3) uncertainty in LOAEL to NOAEL adjustments; and 4) uncertainty in accoun ting for an incomplete database on toxic effects of potential concern. Additional adjustments are often applied to account for uncertainty in extrapolation from observations at one exposure duration (e.g., 4 hours) to arrive at a POD for derivation of an acute reference value at another exposure duration (e.g., 1 hour).

Not all acute reference values are developed for the same purpose and care must be taken when interpreting the results of an acute assessment of human health effects relative to the refe rence value or values being exceeded. W here relevant to the estimated exposures, the lack of threshold values at different levels of severity should be factored into the risk characterization as potential uncertainties.Draft Risk Assessment for the Flexible Polyurethane Foa m Production Source Category

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