Children's Health Protection Advisory Committee
Chair:
Deanna Scher, PhD
Environmental Health Division
Minnesota Department of Health
625 N. Robert Street
St. Paul, MN 55155-2538
(651) 201-4922
Deanna.ScherPstate.mn.us
Committee Members:
Leif Albertson, MS
Rebecca Bratspies, JD
Lori Byron, MD, FAAP
Jose Cordero, MD, MPH
Natasha DeJarnett, PhD
Diana Felton, MD
Julie Froelicher, MEM
Katie Huffling, MS, RN
Maureen Little, DrPH
Linda McCauley, PhD
Mark Miller, MD, MPH
Olga Naidenko, PhD
Ruth Ann Norton
Daniel Price, PhD
Virginia Rauh, SCD, MSW
Perry E. Sheffield, MD, MPH
Derek G. Shendell, D. Env., MPH,
AB
Veena Singla, PhD
Alicia Smith, PhD
Shirlee Tan, PhD
Joyce Thread, MS
KristieTrousdale, MPH
Carmen M. Velez Vega, PhD,
MSW
Yolanda Whyte, MD
Ke Yan, PhD, MS
Marya Zlatnik, MD, MMS
January 26, 2021
Acting Administrator Jane Nishida
United States Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460
RE: Protecting children's health under amended TSCA: Chemical prioritization
Dear Acting Administrator Nishida:
The Toxic Substances Control Act (TSCA) was amended in 2016 by the Frank R.
Lautenberg Chemical Safety for the 21st Century Act. There was clear consensus and a
mandate from Congress that EPA should identify and mitigate risks to human health and
the environment from chemicals, with particular emphasis on protecting the most
vulnerable populations, including children ("potentially exposed or susceptible sub-
populations" in the words of the law).1 Children's health is uniquely susceptible to
adverse impacts from toxic chemicals, and encompasses the health of children as well as
people of reproductive age, pregnant people, and the periods of prenatal and postnatal
development. The Environmental Protection Agency (EPA) has requested input from the
Children's Health Protection Advisory Committee (CHPAC) on TSCA topics that focus on
chemical prioritization and data needs to protect children's health (charge provided in
July 2020, see Attachment A).
EPA previously developed the TSCA Workplan (referred to as "the Workplan") list of
priority chemicals for risk evaluation by considering key hazards, chemical properties, and
potential for human exposure as factors of concern for children's health, including:
reproductive or developmental effects; probable or known carcinogenicity; persistence;
bioaccumulation; use in children's and/or consumer products; and detection in indoor
air, dust and environmental media.2 3 These priorities and several others were affirmed
in the CHPAC's 2011 and 2017 letters and offer a strong scientific foundation for
prioritization and consideration of data needs relevant to children's health (Attachment
B).4;S An additional guiding priority described herein is the consideration of health equity.
In this letter, CHPAC offers EPA recommendations relevant to children's environmental
health in direct response to the four charge questions, which focus on: (1) the evaluation
and prioritization of the remaining Workplan chemicals; (2) the evaluation and
prioritization of other (non-Workplan) chemicals; (3) identification and addressing of
hazard and exposure data gaps; and (4) incorporation of data from New Approach
Methods (NAMs). Rather than reviewing specific Workplan or non-Workplan chemicals,
we focus on providing frameworks, principles, data sources and methodological
approaches whose application will result in chemicals of high concern for children's
health being prioritized, with information relevant for risk assessment provided at the
same time. CHPAC consensus was that this approach provides more long-term value as
EPA can flexibly integrate our recommendations as appropriate and apply them to
additional chemicals in the future.
Children's Health Protection Advisory Committee is a Federal Advisory Committee for the
U.S. Environmental Protection Agency under the Federal Advisory Committee Act
http://vosemite.epa.gov/ochp/ochpweb.nsf/content/whatwe advisorv.htm
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Charge 1: Provide children's environmental health information relevant for prioritization and risk
evaluation of the chemicals remaining on the TSCA Workplan.
Recommendations
• Include consideration of social vulnerability and environmental co-exposures as part of
'potentially exposed or susceptible sub-populations' and/or 'other risk-based criteria' in the
prioritization process to select high-priority chemicals.
• Prioritize chemicals potentially impacting burdened communities by employing data analysis and
visualization to integrate information on chemical and non-chemical stressors.
At present, 53 chemicals remain on the Workplan from which EPA must select at least 50% of high priority
chemicals to undergo risk evaluation every three years (Attachment C). As each of the 53 chemicals must
eventually undergo risk evaluation, we advise EPA to consider information applicable to both prioritization
and risk evaluation. EPA's screening process to create the Workplan list was intended to identify chemicals of
concern for children's health and considered a set of key hazard and exposure factors previously identified by
CHPAC (Attachment B).6 As shown in EPA's 2012 and 2014 Workplans, many of the remaining 53 chemicals
have hazard and/or exposure profiles suggesting children's environmental health concerns. The data sources
and references from the Workplans can serve as a starting point in prioritization.2,3
Considering the prioritization approaches currently used by EPA to identify high priority chemicals, we
recommend beginning with chemicals with consumer product use that also affect people in communities
most burdened by both environmental health hazards and non-chemical stressors that contribute to social
vulnerability.A Chemical use in consumer products, including those marketed to children, is a potential
exposure factor emphasized in the Workplan process, highlighted previously by CHPAC, and considered
under TSCA's Section 6 conditions of use analysis (Attachment B). Social vulnerability and environmental co-
exposures are 'other risk-based criteria' whose consideration supports TSCA's mandate to protect susceptible
populations and is aligned with EPA's Prioritization Rule criteria.7 The evaluation of these criteria by EPA is
also consistent with Executive Order 12898: Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations.8
Populations of concern for children's health (e.g., children, people of reproductive age, pregnant people) in
socially vulnerable groups are more likely to have multiple harmful environmental exposures; higher risks of
adverse biological effects, comorbidities and other chronic stressors; and fewer resources for mitigation.9
Decades of peer-reviewed research demonstrate that chemical exposures can cause more severe adverse
health impacts when combined with social stressors. For example, children in poverty were shown to have
more severe health outcomes from the same level of lead exposures compared to higher-income children.10
Studies also document that limiting toxic exposures has long-term benefits for socially vulnerable
populations.11,12 The ongoing COVID-19 pandemic further highlights how social inequalities profoundly, and
unevenly, impact morbidity and mortality. Therefore, we advise EPA to give high priority to preventing
harmful exposures in vulnerable communities.1317 A strategy prioritizing chemicals disproportionately
impacting vulnerable populations helps ensure the opportunity to be healthy is equally available. This
approach is also aligned with ongoing efforts across the Agency and within all levels of government to
advance health equity, which creates healthier communities and ultimately better health for the entire U.S.
population.
A CDC defines social vulnerability as "the potential negative effects on communities caused by external stresses on
human health. Such stresses include natural or human-caused disasters, or disease outbreaks. Reducing social
vulnerability can decrease both human suffering and economic loss." Source: ATS PR
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To implement an approach incorporating social vulnerability information into TSCA prioritization, CHPAC
recommends prioritizing chemicals with significant overlap of multiple measures of potential risk. Data on
social vulnerability, geographic proximity to environmental exposures, potential co-exposures to other
chemicals with similar health hazard endpoints, and consumer product use are represented in existing
databases and the combined potential risks can be understood through varied data analyses and visualization
tools.
As one approach, EPA could begin with the most recent Chemical Data Reporting and Chemical and Product
Database information to identify which of the 53 remaining chemicals are used in consumer products
including children's products. Then, of the chemicals with consumer product uses, EPA could focus on
chemicals with data reported to the Toxics Release Inventory (TRI), as TRI information allows chemical
releases to air, land and water to be geographically localized.18 Such chemical releases could be important
contributors to exposures potentially impacting toxicity during preconception, prenatal, postnatal and other
sensitive life stages. Attachment C identifies chemical uses from the 2014 Workplan and the chemicals listed
in the TRI.
Geographic Information System (GIS) analysis allows overlay of TRI information for a Workplan chemical with
consumer product use and other geographic information related to risks. One example is social vulnerability
factors in the Centers for Disease Control and Prevention's Social Vulnerability Index.19 8 Another example is
data available in the National Air Toxics Assessment based on emissions modeling of air contaminants that
inform potential co-exposures to other contaminants with similar hazard endpoints of concern, such as
carcinogenicity or respiratory hazard.20
EPA can combine this information with population estimates to prioritize chemicals potentially impacting the
greatest number of socially vulnerable people. Attachment D provides an example summing population
estimates of counties with both high social vulnerability and high volume of TRI releases for two chemicals to
allow comparison. Another approach would be to prioritize chemicals where TRI releases show the greatest
potential for co-exposures relevant to the specific health risk(s) of concern for each of the chemicals being
evaluated. For example, for a chemical with known respiratory toxicity, extensive co-exposures to other
respiratory toxicants may indicate a need for prioritization. General examples of both these approaches are
provided in Attachment D. These approaches are not mutually exclusive and can be combined with each
other and/or with other relevant data sources to inform prioritization and risk evaluation by providing a
more detailed and informative picture of social and environmental factors affecting susceptibility and
vulnerability. Examples of resources with relevant data are provided in Attachment E.
As prioritization precedes the more rigorous process of full systematic review, CHPAC believes the recognized
limitations in the existing databases (e.g., not all chemicals are in TRI; SVI does not include all social risk
factors) need not prevent their utility in establishing the list of priority chemicals. For risk evaluation, EPA
would need to refine this analysis with additional data to address limitations (Attachment E). Additional
considerations are also needed in risk evaluation. For example, it is critical to consider consumer product
exposures in the context of historical or current releases that have led to contaminated air, drinking water
and food that contribute to exposures, as highlighted in previous CHPAC recommendations (Attachment B).
In addition to considering aggregate exposures to a single chemical across multiple routes and pathways as
defined in TSCA regulation,21 we urge EPA to assess cumulative exposures, the combined exposure to
multiple chemical and non-chemical stressors via multiple pathways as outlined in EPA guidance.22 Our
B The Social Vulnerability Index uses 15 metrics to create an index: Below poverty; unemployed; income; no high
school diploma; age 65 or older; age 17 or younger; older than age 5 with disability; single parent households;
minority; speaks English "less than well"; multiunit structures; mobile homes; crowding; no vehicle; group
quarters.
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references to "exposure" throughout this letter encompass the concepts of both aggregate and cumulative
exposures unless otherwise specified.
In summary, the principles for prioritization that CHPAC recommends can be implemented through
employing data analysis and visualization to combine complex and disparate data sources (e.g., chemical use,
exposure, hazard/adverse health risks, non-chemical stressors) on the remaining 53 chemicals. Such analyses
will support EPA in effectively prioritizing the chemicals most likely to impact children and people of
reproductive age in the most burdened communities.
Charge 2: Provide children's environmental health information relevant for prioritization of chemicals
not on the TSCA Workplan.
Recommendation
• Evaluate newly available hazard and exposure information periodically during the prioritization
process, using the TSCA Workplan method to identify non-Workplan chemicals for prioritization.
TSCA allows consideration of non-Workplan chemicals for priority listing. The Workplan approach originally
considered factors relevant to children's environmental health to identify chemicals for screening and
selection (Attachment B). CHPAC recommends that EPA continue to build on this foundation and establish
specific time frames to re-evaluate current data on chemicals not selected for the Workplan (i.e., non-
Workplan chemicals); and use the same process of reviewing authoritative lists to select additional chemicals
for screening. Chemicals selected for screening through the process described in this charge response should
be prioritized using the same approach as described in the response to charge 1 to ensure decisions are
made with full understanding of how they might contribute to environmental health disparities across
populations.
Periodic evaluation of non-Workplan chemicals is important because new hazard data may become available
and exposures may change, which can impact prioritization. Production can increase or new uses of a
chemical may result in increased exposure. Two valuable sources of exposure information to support EPA's
screening of non-Workplan chemicals that are updated with a regular frequency include Chemical Data
Reporting (CDR) and Toxics Release Inventory (TRI) reporting.
Chemicals screened, but not selected, for the Workplan fell into two categories: (1) "Potential candidates for
information gathering" were chemicals without sufficient information on hazard or exposure metrics; and (2)
Chemicals ranked "moderate" or "low" in the 2014 Workplan. Attachment F lists the chemicals screened in
the Workplan process but not selected for the Workplan.
For Category 1 (insufficient information) chemicals, we advise EPA to seek updated data on hazard, exposure,
and adverse human health effects, focusing on the chemical prioritization factors in Attachment B. We
recommend that EPA also consider data and findings from epidemiologic studies, several of which are
highlighted in Attachment E. EPA should score those chemicals which now have sufficient data and consider
those that rank high for earlier prioritization.
For Category 2 (did not rank high in 2014 Workplan process), we recommend EPA evaluate current hazard
data and the most recent CDR and TRI data to see if production volume, uses or releases have changed. EPA
should update normalized total scores and consider chemicals with a higher ranking for prioritization.
We also recommend that EPA review the authoritative lists used to generate the candidate chemicals
screened in the original TSCA workplan process (Attachment G). and additional relevant authoritative lists,
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and consider the need to screen relevant chemicals added to each list since 2012. This approach could
identify chemicals of emerging concern for prioritization. The data sources and references already gathered
from the authoritative listing process may be useful to EPA.
We advise EPA to specifically consider chemical uses in electronics, such as flame retardants, as a relevant
consumer and children's product use, especially in light of the rapid expansion of 'distance learning' due to
the COVID-19 pandemic and the increased use of computers and electronic devices by children as young as
preschool age. We also recommend that EPA analyze biomonitoring data to understand human exposure
trends, as well as environmental monitoring data to assess whether occurrence and concentrations are
increasing in media such as air, indoor dust, or water.
Charge 3: Provide information on data needs relevant to children's environmental health concerns for
prioritization and risk evaluation of the remaining Workplan chemicals.
Recommendations
• Evaluate the completeness of a chemical's database to determine data needs for hazard and
exposure data critical for assessing children's health risks, as described below.
• Employ multiple approaches to address gaps in hazard and exposure data needed to ensure
robust evaluations that do not underestimate children's health risks.
Hazard and exposure information are necessary to complete both prioritization and subsequent risk
evaluations, making it imperative to identify and address data gaps as early in the process as possible. To
determine data needs for potential high priority chemicals, we recommend EPA evaluate the completeness
of a chemical's database for key hazard and exposure data relevant to children's health as described below.
Where data needs are identified, we advise that EPA: (1) use TSCA Section 4 and 8 authorities to collect
additional data; and/or (2) determine how adjustment factors, to account for uncertainty, variability, and
vulnerability, or other health-protective approaches (e.g., predictive modeling) will be used to address the
data gap(s).
TSCA includes the concept of "reasonably available" information which is highly relevant to assessment of
children's environmental health impacts. "Reasonably available" data include the full scope of peer-reviewed
studies available for individual substances and mixtures. As detailed in a February 2020 CHPAC liaison letter
to the EPA Scientific Advisory Board, critical research studies providing key data on children's health risks
likely contain protected health information that would prevent raw data from being made public.23 We
advise EPA to include such studies in its evaluations using a validated systematic review method to evaluate
and integrate the complete body of relevant scientific evidence, resulting in more robust and reliable
evaluations. This recommendation is consistent with the 2020 CHPAC liaison letter which states that "EPA
should not exclude high quality research studies."23
CHPAC fully supports EPA utilizing TSCA Section 4 and 8 authorities to obtain data, including confidential
business information, to inform both the prioritization process and risk evaluations. The TSCA statute allows
health and safety studies received in response to such requests to be made available for public review. As
industry-sponsored studies do not typically undergo peer review, we recommend that industry-sponsored
studies obtained from EPA requests undergo expert review to ensure a full understanding of the findings,
strengths, limitations and appropriate use of such data. We also encourage EPA to use relevant data and
findings from epidemiologic research (examples in Attachment El-
Multiple approaches to address data needs
In addition to obtaining needed data using TSCA Section 4 and Section 8 authorities, we concur with the
National Research Council's recommended use of adjustment factors and other health-protective approaches
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to account for "missing defaults" and other data gaps.24 The need to use adjustment factors that account for
life-stage vulnerability is also highlighted in CHPAC's 2017 letter to the EPA on TSCA implementation.5
While it is standard to apply adjustment factors to account for inter- and intra-species variability in chemical
risk assessment, EPA must consider additional sources of uncertainty, variability, and vulnerability that are
pertinent to children's health in non-cancer risk assessment. Some examples include database uncertainty in
relation to a critical hazard endpoint or exposure, life stage differences in how a chemical is metabolized, and
early life susceptibility such as in utero exposure to developmental toxicants. The database uncertainty factor
is relevant to the question of data gaps and has not yet been incorporated in TSCA risk assessments. We
advise EPA to follow recommendations and established best practices detailed in Agency documents on the
use of the database uncertainty factor.25 Uncertainties, variabilities and vulnerabilities should be
quantitatively addressed in risk assessment to avoid underestimating children's health risks.24
In general, grouping/categorization approaches to chemicals can be helpful to identify similar data needs,
and approaches to addressing them, across similar chemical groups. There are numerous valid approaches to
grouping chemicals and we suggest several here, though this is not a comprehensive list.
First, chemicals can be grouped around the potential to increase adverse health impacts, whether through
common hazards, exposures, or both. For example, a group could be chemicals with common co-exposures,
such as benzene, toluene, ethyl benzene and xylenes (BTEX) related to fossil fuels. A group could also be
chemicals with similar adverse health endpoints, such as female reproductive toxicity. Chemicals known to
contribute to cumulative impacts in vulnerable populations, which could be identified by approaches
outlined in the response to charge question 1, could also be grouped.
Second, chemicals can be grouped according to common chemical characteristics of concern, such as
predicted toxicity or chemical properties like persistence and bioaccumulation. For example, several
ethanones raise persistence and bioaccumulation concerns.
Third, chemicals can be grouped to support informed substitution and ultimate risk mitigation, when
chemicals have similar functional uses and may be used as substitutes for each other. For example, flame
retardants used in consumer products could be grouped.
Finally, there may be categories of chemicals where grouping for evaluation may not be helpful, but where
the chemicals have similar data needs. For example, several chemicals remaining on the Workplan can be
used as components of polymers (bisphenol A, vinyl chloride, styrene) and thus may have similar data needs
related to assessing unique hazards and exposures across the chemical life cycle.
Data needed on key hazards relevant to children's health
We concur with previous CHPAC recommendations highlighting the following hazards as of most significant
concern for children's health (Attachment B):
• Reproductive toxicity
• Developmental toxicity (including developmental neurotoxicity)
• Carcinogenicity
• Endocrine toxicity, including metabolism disrupting chemicals
• Respiratory toxicity and potential effects on lung development, structure or function
• Immunotoxicity
• Toxicity through preconception and/or in utero exposures
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The current COVID-19 pandemic highlights the importance of immunotoxicity in contributing to disease risk
and reveals how there are often data gaps on how chemical exposures affect the immune system and
ultimately, the clinical disease course.26,27 There are existing regulatory assays relevant to immunotoxicity
which could be utilized.28
EPA's existing risk assessment guidelines appropriately outline the type of information needed to evaluate
hazards (examples in Attachment H). Ensuring that sufficient information is available on each relevant health
endpoint category can provide better grounds for hazard determinations. Regarding endocrine toxicity, we
recommend that EPA use the principles outlined by the Endocrine Society as described in CHPAC's 2017
letter.29 As detailed below, cell-based assays and other high-throughput toxicity tests, often called New
Approach Methods (NAMs), have the potential to provide needed data and could be used to establish
potential hazards or upgrade overall hazard identification. However, due to important limitations, data from
NAMs cannot be used to rule-out a specific hazard.
Research has established how, for certain endpoints, the developing organism can be significantly more
sensitive to exposure than the adult organism. Endpoint sensitivity can be determined through dose-
response assessment or other approaches, such as outlined by the National Research Council.30,31 EPA should
prioritize filling data gaps on a chemical's impact on the developing organism for risk assessment. In the
event that studies specifically addressing early life sensitivity are not available, adjustment factors should be
applied.
Additionally, data needed to integrate life stage susceptibility into the quantitative risk calculation must be
identified to set priorities for data requests and examine risk for specific chemicals. The needed data may be
chemical-specific, as human variability in response to chemical exposure has been shown to vary widely, and
in some cases may exceed the default's maximum 10X value.32 Data on broader categories of chemicals are
also available to inform use of an adjustment factor; for example, adjustment factors for asthma-inducing
chemicals.32 To protect the public, we urge development and use of appropriate adjustment factors for each
of the life stages. CHPAC has previously provided data and resources for assessing the susceptibility of
different life stages to chemicals or mixtures.5
Data needed on key exposures relevant to children's health
Previous CHPAC letters have highlighted the need for the following exposure information relevant for
children's health (Attachment B):
• Use in consumer/children's products
• Ubiquitous in environments, foods or products in the U.S.
• Biomonitoring, especially information on chemicals that can cross the blood-brain barrier or
placenta, and detection in children, women of reproductive age, cord blood, breast milk and
pregnant women
• Presence in drinking water, including private wells
• Presence in breast milk and/or food consumed by infants, children, and women of child-bearing age
• Presence in indoor air and dust, including indoor gyms and places children play indoors
• Presence in outdoor environmental media, especially outdoor soil, and surfaces and structures
where children may play or spend time
• Presence inside, outside and adjacent to child care or school settings
• Presence in occupational settings where parents or people of reproductive age work
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We advise EPA to determine the completeness of the database on the exposures listed above, including how
widespread the use of the chemical is, or is anticipated to be, in the home, schools, parks or other areas
where children may spend time.
For key exposures listed above, sufficient data must be available in order to:
• Quantitatively assess each relevant exposure source and pathway
• Understand potential exposures during the chemical's life cycle, including manufacturing,
processing, distribution in commerce, use and disposal
• Integrate exposures into a total risk calculation where co-exposures by different routes are expected
to occur together (such as inhalation and dermal exposures from product use)
• Integrate exposures into a total risk calculation where exposures from different sources are expected
to occur in the same population (such as people of reproductive age who may be exposed to a
chemical on the job and also at home from use of a consumer product containing the same
chemical)
• Integrate exposures into a total risk calculation where co-exposures to different agents occur and
impact similar health endpoints (such as multiple agents with impacts on lung function)
CHPAC therefore urges EPA to consider the data needed to assess each relevant exposure as described above
in a risk evaluation. As part of its prioritization strategy, EPA should develop plans to obtain the needed data
or utilize adjustment factors or other health-protective approaches. Additionally, exposure assessment
should make use of analytic strategies most appropriate for the evaluation of aggregate exposures.
A preliminary review of data on the 53 Workplan chemicals available on PubMed indicates a lack of key
hazard and exposure data, highlighted above, for many of the chemicals (Attachment C). CHPAC's review
suggests the need for EPA to develop strategies to address these children's health data gaps. For high priority
chemicals, EPA should also gather data on common chemical co-exposures and social stressors in exposed
populations (resources in Attachment E). Many tribes, states, and local jurisdictions have regional data that
may address information gaps and provide data needed for hazard identification, co-exposure and co-
stressor impacts. The Committee listed many of these resources in Attachment E and suggests that tribal,
state, and local jurisdictions can serve as valuable partners.
Charge 4: Provide information relevant to evaluating children's environmental health concerns with
New Approach Methods (NAMs) on EPA's list or in development.
Recommendations
• Limit use of data from New Approach Methods (NAMs) for: screening purposes; indicating hazard;
upgrading hazard concern; and adding or increasing adjustment factor(s).
• Use data from NAMs in conjunction with data considering susceptible and vulnerable
subpopulations.
• Support independent scientists, public health practitioners and physicians in the collaborative
development and review of NAMs specific to children's environmental health.
Section 4(h)(2) (C) and (D) of TSCA requires EPA to develop a list of NAMs that are "scientifically reliable,
relevant, and capable of providing information of equivalent or better scientific reliability and quality to that
which would be obtained from vertebrate animal testing" along with criteria "for considering scientific
reliability and relevance" of NAMs. Many approaches for the use of NAMs in toxicology are under
development.33"38 Work in this area is rapidly evolving as are the approaches to using these tools in a
regulatory context. While the strength of NAMs lies in their ease of use and reduction of animal testing,
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CHPAC has not identified any approaches that can currently be paired with NAMs to accurately identify the
complex biological responses to chemicals of greatest concern for children's health. Improving EPA's ability
to protect children's health through appropriate use of NAMs will require investments in newer methods to
better address chronic diseases, developmental disorders, immunologic changes, epigenetic mechanisms,
and pre-and perinatal exposures. While EPA awaits the development of methods and regulatory approaches
that can utilize NAMs to capture more complex biological processes, we emphasize the NAMs and their
development should not hinder the use of existing methods, slow the improvement of traditional methods,
or prevent the development of new in vivo approaches, which may be more effective in protecting children's
health.
Concerns about the ability of current NAMs to inform children's environmental health
In general, EPA's current list of NAMs does not identify which methods, if any, are applicable to assessment
of hazards, exposures or susceptibilities relevant to children's health.39 EPA should clarify how the listed
NAMs will be used to provide data on children's environmental health concerns.
There are currently no assays that can capture the most critical hazard endpoints for children's health where
complex biological systems are involved (such as reproductive and developmental toxicity;
neurodevelopmental toxicity; placental development). The listed NAMs contain some assays relevant to
children's health, including estrogen/androgen receptor binding and transactivation, steroidogenesis, and
skin/eye irritation. Several of these assays evaluate chemicals for their intrinsic ability to interfere with
hormone signaling.
However, the current methods are lacking in key aspects needed to generate data relevant for children's
health, such as: assessing non-monotonic dose responses (NMDR); low-dose effects; imbalances and
reactive/feedback changes in complex hormonal systems (e.g. hormone synthesis, transport and
metabolism); upstream effects that may indicate adversity; sensitivity to exposure during critical
developmental stages; and, context dependent features such as tissue, receptor type, and co-factors that
may affect hormone signaling.
The development of exposure and hazard models on the TSCA NAMs list, and the assumptions within them,
should be transparent. Prior to adding new NAMs to the EPA list, we recommend EPA seek public and expert
review of each NAM to ensure a full understanding of the strengths, limitations and appropriate use to
inform prioritization and risk evaluation.
Recommendations on usinE data from NAMs to inform children's health protection and further methods
development
Due to the limitations noted above, CHPAC recommends listed NAMs be used for screening purposes and to
indicate a hazard or upgrade concern for a hazard, but conclusions about the absence of hazard cannot be
drawn solely based on NAMs data. Therefore, we advise that data from these alternative methods should not
be used to reduce default adjustment factors but could be used to add or increase such a factor. We also
recommend that EPA use the most protective testing strategies to generate information on a broad range of
endpoints, including disease-focused endpoints that may include upstream indicators, and not solely the
traditional guideline study endpoints which miss many developmental stages and sensitivities.40
When applying data from a more studied chemical to a less studied, but related, chemical ("read across"),
hazard models should only be used to assume that analogs are at least as toxic as the parent chemical, not to
assume that analogs are less toxic. Exposure and hazard models must consider or be used in conjunction with
information considering susceptible and vulnerable subpopulations, including developmental stages,
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geographic location, environmental justice considerations, sex-specific effects, and other factors known to
affect biological susceptibility and vulnerability. Environmental justice considerations include factors outlined
in the response to charge 1 above, such as co-exposure to multiple chemical and non-chemical stressors.
We advise EPA to continue considering NAMs approaches that are fully transparent and developed in
collaboration with independent scientists, including those in the public health and medical communities.
Collaborative development of alternative methods could be more strategically directed if the purpose of the
assays were well defined, including how EPA would use the data to inform decisions. We recommend that
EPA support the collaborative development and review of NAMs by independent scientists and physicians
with expertise in reproductive and developmental biology, endocrinology, hormonal systems, and neuronal
development. EPA should also seek input and meaningful involvement from the public, including
communities most impacted by the chemicals being assessed.
We emphasize the key characteristics framework for EPA here as it has particular strengths to organize data
streams (including data from NAMs) in a clear way, to demonstrate the strength of evidence for different
data streams, and to highlight gaps needed to further assess a chemical and its impacts. Essential
characteristics have been developed for carcinogens, endocrine disrupters and male and female reproductive
toxicants, with additional hazard endpoints in development.41"45 The key characteristics framework could be
utilized independently or in a complementary way with other approaches (e.g., adverse outcome pathways,
integrated approaches to testing and assessment, and "-omics" large datasets) and would be directly
compatible with a systematic review approach.
In closing, the approaches outlined in our letter will support EPA in strong TSCA implementation, and thus
lead to better health protections from toxic chemicals for the most vulnerable population groups and
ultimately healthier children and families throughout the U.S. population. Thank you for the opportunity to
comment and we look forward to our continued engagement on the protection of children's health.
Sincerely,
—
Deanna Scher, Ph.D.
Chair
cc: Jeanne Briskin, Director, Office of Children's Health Protection
Michal Freedhoff, Principal Deputy Assistant Administrator, Office of Chemical Safety and
Pollution Prevention
Lindsay Hamilton, Associate Administrator, Office of Public Affairs
Nica Louie, CHPAC Designated Federal Official, Office of Children's Health Protection
Dan Utech, Chief of Staff, Office of the Administrator
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January 26, 2021
References
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34. Organisation for Economic Co-operation and Development (OECD). Integrated Approaches to Testing and
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animals in chemical testing. 2020. https://www.epa.gov/sites/production/files/2020-
06/documents/epa nam work plan.pdf
39. U.S. Environmental Protection Agency (USEPA). List of alternative test methods and strategies (or new
approach methods [NAMs]). 2018. https://www.epa.Eov/sites/production/files/2018-
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40. Woodruff Tracey J, Zeise L, Axelrad Daniel A, Guyton Kathryn Z, Janssen S, Miller M, Miller Gregory G,
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127(7):75001.10.1289/ehp4971
45. Key Characteristics. Projects and future planned projects, https://keycharacteristics.org/
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Attachments
Attachment A: Amended TSCA Workgroup Charge for the Children's Health Protection Advisory
Committee (CHPAC) 15
Attachment B: Table of chemical prioritization factors 20
Attachment C: 53 remaining TSCA workplan chemicals: Initial review of children's environmental health
information and data gaps 21
Attachment D: Example GIS Analysis 40
Attachment E: Resources for social vulnerability and environmental co-exposure information 44
Attachment F: Chemicals not on TSCA Workplan to consider for prioritization 47
Attachment G: Authoritative sources used for TSCA Workplan method 59
Attachment H: Excerpts from EPA risk assessment guidelines 60
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Attachment A: Amended TSCA Workgroup Charge for the Children's Health Protection Advisory
Committee (CHPAC)
SCOPE
OPPT and OCHP are working to establish a new CHPAC workgroup to provide children's environmental health
(CEH) expert input on the chemicals remaining in the 2014 TSCA Workplan after the 20 high- and 20 low-
priority chemicals were designated in December 2019. Children's health includes the health of pregnant
women, prenatal development, and postnatal development from birth through puberty. Under this charge,
the CHPAC would identify recommendations for CEH implications for the remaining chemicals on the Work
Plan, including which chemicals have children's health relevant data gaps where OPPT could seek reporting
or testing under Sections 8 and 4, respectively.
BACKGROUND
TSCA, as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act (2016,) states that
"potentially exposed or susceptible subpopulations" ("PESS") be considered in the risk evaluation process.
"The Administrator shall conduct risk evaluations pursuant to this paragraph to determine whether a
chemical substance presents an unreasonable risk of injury to health or the environment, without
consideration of costs or other nonrisk factors, including an unreasonable risk to a potentially
exposed or susceptible subpopulation identified as relevant to the risk evaluation by the
Administrator, under the conditions of use." (Public Law 114-182; 6[b][4][a])
Further, TSCA amendments specifically calls out infants, children, and pregnant women as examples of PESS:
"The term 'potentially exposed or susceptible subpopulation' means a group of individuals within the
general population identified by the Administrator who, due to either greater susceptibility or greater
exposure, may be at greater risk than the general population of adverse health effects from exposure
to a chemical substance or mixture, such as infants, children, pregnant women, workers, or the
elderly." (Public Law 114-182; Section 3[12])
Under TSCA, EPA considers PESS, including developmental life stages, in its risk evaluations.
Prioritization
The first step in the TSCA process is prioritization. EPA's process and criteria for prioritization
the Procedures for Prioritization of Chemicals for Risk Evaluation Under the Toxic Substances
("Prioritization Rule"), finalized in June 2017. The Prioritization Rule requires that EPA screen
available information for chemicals using the following criteria and considerations:
(1) "The chemical substance's hazard and exposure potential;
(2) The chemical substance's persistence and bioaccumulation;
(3) Potentially exposed or susceptible subpopulations;
(4) Storage of the chemical substance near significant sources of drinking water;
(5) The chemical substance's conditions of use or significant changes in conditions of use;
(6) The chemical substance's production volume or significant changes in production volume; and
(7) Other risk-based criteria that EPA determines to be relevant to the designation of the chemical
substance's priority."
The 3rd criterion (above) on PESS has relevance to CEH and the other six criteria (above) have potential
relevance to CEH. After public comment on the candidate chemicals, a screening review step results in
proposed priority designations. After a public comment period on the screening and priority designations,
EPA will designate chemicals either as low-priority substances or as high-priority substances for risk
are described in
Control Act
the reasonably
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evaluation. On December 20, 2019, EPA designated 20 high-priority and 20 low-priority substances. Upon
completion of each risk evaluation thereafter, EPA must designate another high-priority chemical for risk
evaluation. Under TSCA section 6(b)(2)(D) EPA must give preference to chemicals that:
• have a "persistence and bioaccumulation score of 3"; and
• "are known human carcinogens and have high acute and chronic toxicity
Chemicals not on the 2014 TSCA Workplan can also be nominated for consideration as high-priority
substances under TSCA. However, under TSCA section 6[b] [2] B], EPA is required to select at least 50 percent
of chemical substances for risk evaluation from the 2014 Workplan:
"ADDITIONAL RISK EVALUATIONS.—Not laterthan three and one half years after the date of
enactment of the Frank R. Lautenberg Chemical Safety for the 21st Century Act, the Administrator
shall ensure that risk evaluations are being conducted on at least 20 high-priority substances and
that at least 20 chemical substances have been designated as low-priority substances, subject to the
limitation that at least 50 percent of all chemical substances on which risk evaluations are being
conducted by the Administrator are drawn from the 2014 update of the TSCA Work Plan for Chemical
Assessments."(Sec. 6[b][2][B])
Data Request Authority:
TSCA has provisions for requesting data and requiring reporting from manufacturers and processors under
Sections 4 and 8, respectively.
Under TSCA 4[a][1], EPA has "Testing Requirements" in the context of risk evaluations. The language below
requires EPA, by rule, order, or consent agreement, to require testing on a substance in certain instances,
such as when there is insufficient information and additional data is necessary for risk evaluation purposes.
This section on Testing Requirements states-
"If the Administrator finds that—(A) (i)( I) the manufacture, distribution in
commerce, processing, use, or disposal of a chemical substance or mixture, or
that any combination of such activities, may present an unreasonable risk of
injury to health or the environment,
(II) there is insufficient information and experience upon which the effects of
such manufacture, distribution in commerce, processing, use, or disposal of such
substance or mixture or of any combination of such activities on health or the
environment can reasonably be determined or predicted, and
(III) testing of such substance or mixture with respect to such effects is necessary
to develop such information; or
(H)(1) a chemical substance or mixture is or will be produced in substantial
quantities, and (aal) it enters or may reasonably be anticipated to enter the
environment in substantial quantities or (bbll) there is or may be significant or
substantial human exposure to such substance or mixture,
(II) there is insufficient information and experience upon which the effects of the
manufacture, distribution in commerce, processing, use, or disposal of such
substance or mixture or of any combination of such activities on health or the
environment can reasonably be determined or predicted, and
(III) testing of such substance or mixture with respect to such effects is necessary
to develop such information;" (Sec 4[a][l])
Under TSCA 4(a)(2)(A)(i), EPA has "Additional Testing Authority" -
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"the Administrator may, by rule, order, or consent agreement—
(A) require the development of new information relating to a
chemical substance or mixture if the Administrator determines that the
information is necessary—
(il to review a notice under section 5 or to perform a risk
evaluation under section 6(b);" (Sec 4[a][2][A][i])
Under TSCA 4[a][2][B], "Additional Testing Authority," in the context of prioritization, states that EPA may -
"require the development of new information for the purposes of prioritizing a chemical substance
under section 6(b) only if the Administrator determines that such information is necessary to
establish the priority of the substance, subject to the limitations that—
[il not later than 90 days after the date of receipt of information
regarding a chemical substance complying with a rule, order, or
consent agreement under this subparagraph, the Administrator shall
designate the chemical substance as a high-priority substance or a
low-priority substance; and
(ii) information required by the Administrator under this subparagraph
shall not be required for the purposes of establishing or implementing
a minimum information requirement of broader applicability."
Reporting Authority:
Under Section 8(a), EPA has the authority to write rules to require manufacturers and processors to maintain
records and submit reports in order to enforce TSCA.
"The Administrator shall promulgate rules under which—
(A) each person (other than a small manufacturer or processor)
who manufactures or processes or proposes to manufacture or process
a chemical substance (other than a chemical substance described in
subparagraph (B)(ii) shall maintain such records, and shall submit to
the Administrator such reports, as the Administrator may reasonably
require, and
(B) each person (other than a small manufacturer or processor)
who manufactures or processes or proposes to manufacture or
process—
(i) a mixture, or
(ii) a chemical substance in small quantities (as defined by the
Administrator by rule) solely for purposes of scientific
experimentation or analysis or chemical research on, or analysis
of, such substance or another substance, including any such
research or analysis for the development of a product, shall
maintain records and submit to the Administrator reports but only
to the extent the Administrator determines the maintenance of
records or submission of reports, or both, is necessary for the
effective enforcement of this Act." (Sec. 8[a][l])
"The Administrator may require under paragraph (1) maintenance of
records and reporting with respect to the following insofar as known to
the person making the report or insofar as reasonably ascertainable:
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(A) The common or trade name, the chemical identity, and
molecular structure of each chemical substance or mixture for which
such a report is required.
(B) The categories or proposed categories of use of each such
substance or mixture.
(C) The total amount of each substance and mixture
manufactured or processed, reasonable estimates of the total amount
to be manufactured or processed, the amount manufactured or
processed for each of its categories of use, and reasonable estimates
of the amount to be manufactured or processed for each of its
categories of use or proposed categories of use.
(D) A description of the byproducts resulting from the
manufacture, processing, use, or disposal of each such substance or
mixture.
(E) All existing information concerning the environmental and
health effects of such substance or mixture.
(F) The number of individuals exposed, and reasonable estimates
of the number who will be exposed, to such substance or mixture in
their places of employment and the duration of such exposure.
(G) In the initial report under paragraph (1) on such substance or
mixture, the manner or method of its disposal, and in any subsequent
report on such substance or mixture, any change in such manner or
method." (Sec. 8[a][2])
Alternative Test Methods:
Section 4[h] of TSCA directs the reduction of testing on vertebrates (Sec 4[h][1]) and the implementation of
"alternative test methods," (Sec 4[h][2]) defined as those that are scientifically valid and not based on
vertebrate species. These alternative methods could include -
"(i) computational toxicology and bioinformatics;
(ii) high-throughput screening methods;
(Hi) testing of categories of chemical substances;
(iv) tiered testing methods;
(v) in vitro studies;
(vi) systems biology;
(vii) new or revised methods identified by validation bodies such as the Interagency Coordinating
Committee on the Validation of Alternative Methods or the Organization for Economic Co-operation and
Development; or
(viii) industry consortia that develop information submitted under this title." (Sec. 4[h][2])
CHARGE QUESTIONS
1) Referring to the text from TSCA and the Prioritization Rule (above), please review the remaining
TSCA Workplan chemicals for potential CEH concerns (e.g., exposure, effects, and emerging issues),
a. Please provide a compilation of the scientific information supporting potential CEH
concerns, including data sources and references for the remaining chemicals on the TSCA
workplan.
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b. For any chemical with information that indicates a potential CEH concern, please specify and
comment on whether the available information is relevant for the intended use of risk
evaluation. If criteria #7 (above) is a consideration, please describe the "Other risk-based
criteria..." used to justify the CEH level of concern.
c. Please provide a narrative regarding the degree of clarity and completeness of the
documentation associated with the generation of the provided information.
2) While EPA is required to select 50% of their priority chemicals from the 2014 Workplan (see above),
other chemicals can be nominated for high and low priority chemicals under TSCA. Are there
chemicals beyond those remaining on the Workplan that should be considered for prioritization? If
so, provide a list of these non-Workplan chemicals along with the information indicated in question 1
above for consideration.
3) Referring to the text on EPA's authority to request new data and report on existing data from a
manufacturer in Sections 4 and 8 (see above), among the remaining Work Plan chemicals, which
ones with potential CEH concern have significant data gaps which could be addressed by obtaining
data, including through either the Section 4 or Section 8 mechanisms?
a. For example, are there chemicals currently on the workplan list to which children have high
exposure but for which additional health effects data may be needed (or vice versa)?
b. For the specific chemicals on the workplan, what assays or types of studies may be needed
to adequately assess CEH exposure or effects in order to prioritize chemicals on the Work
Plan list or to conduct the Risk Evaluation?
4) Referring to the text on alternative test methods (above) from Section 4[h] of TSCA, EPA has
published a List of Alternative Test Methods and Strategies (or New Approach Methodologies
[NAMs] (see: https://www.epa.gov/sites/production/files/2018-
06/documents/alternative testing nams list june22 2018.pdf)). EPA has also committed to
updating this list periodically as new methods become available. Are there any alternative test
methods, either currently available (on EPA's current list) or under development, that are relevant to
developmental life stages and could be used for testing TSCA chemicals for CEH exposure or effects?
If so, please provide as much information as possible about these methods, and how they are
particularly relevant to CEH concerns.
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Attachment B: Table of chemical prioritization factors
Factor
TSCA
workplanc
CHPAC 2011
letter0
CHPAC 2017
letterE
TSCA
regulation1"
Hazards
Reproductive or developmental effects
X
X1
X2
Probable or known carcinogens
X
X
X
Endocrine disruption
X
X
Respiratory toxicity/effects on lung development,
structure or function
X
Immunotoxicity
X
Presents hazard to children through preconception and/or
in utero exposures
X
High acute and chronic toxicity
X
Chemical Properties
Persistence
X
X
X
Bioaccumulation
X
X
X
Exposure Potential
Used in children's products
X
X
X
X3
Used in consumer products
X
X
X
X3
Ubiquitous in environments, foods or products in the US
X
X4
Detected in biomonitoring
X
X5
X6
Detected in biota
X
Detected in drinking water
X
X
Detected in food consumed by infants, children, pregnant
and/or lactating women
X
Detected in indoor air
X
X
Detected in indoor dust
X
X
Detected in environmental media
X
X7
Detected in childcare and/or school settings
X
Detected in occupational settings where children, parents,
reproductive age people work
X
Volume of releases reported to Toxics Release Inventory
X
Production volume
X
Xs
Storage near significant sources of drinking water
X
Misc.
Other risk-based criteria determined to be relevant to the
designation of the chemical substance's priority
X
highlights developmental neurotoxicity
2Highlights developmental toxicity
3Criteria are "exposure potential" and "conditions of use or significant changes in the conditions of use"
"Highlights "chemicals children are likely to encounter"
5Highlights chemicals that can cross placenta or blood-brain barrier
6Highlights chemicals detected in children, women of reproductive age, cord blood, pregnant women
7Highlights outdoor soil, surfaces and structures where children may play or spend time
8Criteria are "Production volume or significant changes in production volume"
c US EPA, TSCA Workplan Chemicals: Methods Document. (2012)
D CHPAC, Criteria for identifying chemicals of concern for children (including prenatal and preconception
exposures. (March 2011)
E CHPAC, Protecting children's health under amended TSCA. (March 2017)
F 82 FR 33753
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Attachment C: 53 remaining TSCA workplan chemicals: Initial review of children's environmental health information and data gaps
A more detailed Excel file of this attachment is available upon request.
N/A= Not available; No relevant studies were identified in the PubMed search findings (see search terms used in footnote 2).
Yellow highlighted cells = few or no studies identified in PubMed search (see search terms used in footnote 2).
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Acetaldehyde
(75-07-0)
Consumer;
Industrial
TRI: Y
Adolescents: e-cigarettes, waterpipe
smoking, and alcohol; outdoor air
pollutant generated by industrial and
road traffic; pediatric surgical smoke;
childcare facilities
N/A
N/A
Associations: e-cigarettes and
asthma; alcohol-based
mouthwash and oral cancer;
alcohol and Fetal Alcohol
Spectrum Disorders; in utero
acetaldehyde and PNET in
children
N/A
Acrylon itrile
(107-13-1)
Consumer;
Dispersive;
Industrial
TRI: Y
Indoor environmental tobacco smoke
as a VOC metabolite; production of
synthetic fibers, rubber, plastics
including plasticizer in toys; exposure
as a VOC in cribs at neonatal intensive
care units
Smoking was positively
associated with metabolites
of the tobacco constituents
including acrylonitrile in
pregnant women;
acrylonitrile metabolites
associated with ETS; Children
6-11 yrs (NHANES) had
statistically significantly
higher levels of the
metabolite acrylonitrile-vinyl
chloride-ethylene oxide than
nonsmoking adults.
N/A
Associations: Occupational
exposure and menstrual disorder
and dysgenesis in female workers
and the wives of male workers.
N/A
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Acting Administrator Nishida
Page 22
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
tert-Amyl methyl
ether
(994-05-8)
Consumer;
Industrial
TRI: N
Gasoline additive
N/A for children's studies.
Blood and urine
concentrations measured in
healthy male volunteers (not
known whether adolescents
included) exposed to tert-
Amyl methyl ether (TAME)
via inhalation of gasoline;
Driver studies of TAME in
blood and urine.
N/A
N/A
Developmental toxicity: rat,
mice, zebrafish. Effects after
gestational exposure include
fetal deaths, reduced fetal
bodyweight, increased cleft
palate incidence, enlarged
lateral ventricles of the
cerebrum, and craniofacial
abnormalities.
Antimony and
Antimony
Compounds
(category)
Consumer;
Industrial
TRI: Y
Children dietary exposure (China):
average exposure of the population on
antimony in 3 age groups exceeded
WHO ADI (0. 86ng/kg BW); Prenatal
exposure to antimony (Japan).
Identified in maternal blood,
cord blood, and placenta
(Japan); Hair levels
significantly higher in girls
than boys (Iran); High blood
levels in children (Uganda,
Romania); levels in urine
higher in children who ate
more vegetables (Spain).
Detected- levels varied.
Associations: Antimony exposure
and ADHD; Prenatal exposure and
birth outcomes and development,
including cellular function, aging,
girl's puberty, and disease
susceptibility.
N/A
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Acting Administrator Nishida
Page 23
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Arsenic and Arsenic
Compounds
(category)
Consumer;
Industrial
TRI: Y
Arsenic (As) in drinking water (Mexico);
Dietary exposure of inorganic arsenic
(iAs) in children (Spain).
Equivalent (BE) value for As
of 15 |_ig/L in children's urine
(Mexico); urinary iAs
detected (Spain); geometric
mean (GM) for total As in
urine 33.82 for school
children aged 6 -11 years
(Spain); GM fortotal arsenic
was 12.9 iJg/L in urine for 7
year old children (Italy).
Detected- levels varied
Associations: Neuropsychological
development (Spain); possible
kidney damage in children
(Mexico); diabetes-related
outcomes 14+ yrs old (American
Indian tribes); adverse pregnancy
outcomes (e.g., spontaneous
abortion, stillbirth and low birth
weight); genetic damage in
children exposed to As in drinking
water (West Bengal, India).Review
by Young et al. suggests in utero
and postnatal As exposure could
increase risk of adult disease (e.g.,
cancer, cardiovascular disease,
non-alcoholic fatty liver disease,
and diabetes).
Developmental
neurotoxicity; male
reproductive toxicity
Barium Carbonate
(513-77-9)
Consumer;
Industrial
TRI: N
Pesticide; Used in cement production;
laboratory worker exposure.
N/A for children's studies
N/A
N/A for children's studies.
Ingestion and hypokalemia that
can lead to tachycardia,
hypertension or hypotension,
muscle weakness, and paralysis.
N/A
Benzenamine
(62-53-3)
Consumer;
Industrial
TRI: Y
Sparse information.
Dyes: Case report of 16 yr old girl
exposed in paint and dye-casting
factory using aniline dyes.
No children's studies.
Biomonitoring studies: aniline
urinary studies and levels
higherfrom occupational
exposure.
N/A
Case report: 16 yr old girl working
in a paint and dye-casting factory
of aniline dyes presented with
cyanosis, fever and altered
sensorium; Parental occupational
aniline exposure increased risk of
acute lymphocytic leukemia in
children.
Developmental toxicity;
Developmental
neurotoxicity, Reproductive
toxicity.
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Acting Administrator Nishida
Page 24
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Benzene
(71-43-2)
Consumer;
Dispersive;
Industrial
TRI: Y
Tobacco smoke; air pollutants; and in
polymers, resins, synthetic fibers; 6-12
yr old children exposed while working
with solvents (Mexico); Parental
occupational exposure for machine or
engine mechanics, in the shoe industry,
or in nail salons.
Elevated levels of benzene in
blood and urine of children
(Kinshasa/DRC).
Detected- levels varied
Associations: Kidney damage in
children (Mexico); childhood
exposure and risk of acute
lymphocytic leukemia (ALL) and
acute myeloid leukemia (AML); Air
pollution, including benzene,
increases ADHD risk; Nail salon
occupational exposure (could
include adolescents 16+ yrs old) to
volatile organic compounds like
benzene can lead to cancers (e.g.,
squamous cell carcinoma,
nasopharyngeal cancer, Hodgkin's
lymphoma, and leukemia)
(Colorado); Maternal and paternal
occupational benzene exposure
increased risk for childhood
cancer.
N/A
Bisphenol A (BPA)
(80-05-7)
Consumer;
Industrial
TRI: Y
Used to synthesize polycarbonate
plastics and epoxy resins, including in
dental sealants.
83% of hair samples at
concentrations 24 to 1427
ng/g (Spain); BPA urinary
concentrations detected in
nearly all children sampled
(Europe); children 6 to 8 yrs
old had higher BPA levels
than older children (Canada).
Detected- levels varied
Associations: increased risk of
obesity, AD/hyperactivity and/or
ASD in children; disrupts placental
epigenetics; prenatal urinary BPA
concentration associated with
child behavior and cognitive
abilities (associations stronger for
boys than girls).
Effects on steroid hormone
and vitamin D3 metabolism
in rats after postnatal
developmental exposure.
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Acting Administrator Nishida
Page 25
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Fluman biomonitoring data2
Breastmilk Detection/Levels2
Fluman Flealth Outcome Data2
Animal Effects Data2
Butanamide, 2,2'-
[(3,3'- dichloro[l,l'-
biphenyl]- 4,4'-
diyl)bis(azo)]bis[N-
(4-chloro-2,5 -
dimethoxyphenyl)-
3-oxo- (Pigment
Yellow 83)
(5567-15-7)
Consumer;
Industrial
Search results for "pigment yellow"
since no results for pigment yellow 83:
Exposure through tattooing in young
adults; Azo colorant dyes exposure in
workers
N/A
N/A
N/A
N/A
Butanamide, 2-[(4-
methoxy-2-
nitrophenyl) azo]-
N-(2-
methoxyphenyl)-3-
oxo- (Pigment
Yellow 65) (6528-
34-3)
Consumer
TRI: N
Search results for "pigment yellow"
since no results for pigment yellow 65:
Exposure through tattooing in young
adults; Azo colorant dyes exposure in
workers
N/A
N/A
N/A
N/A
4-sec-Butyl-2,6-di-
tert-butylphenol
(17540-75-9)
Consumer;
Industrial
TRI: N
N/A
N/A
N/A
N/A
N/A
Cadmium and
Cadmium
Compounds
(category)
Consumer;
Industrial
TRI: Y
Prenatal and postnatal exposure (e.g.,
coal smoke) (Bangladesh); Dietary
exposure in infants (France); e-waste
recycling exposure in children; Coal
smoke as airborne cadmium source
from heating stoves (Mongolia).
Measured Cd in blood, feces,
and urine (Zambia); Metal
levels higher in 0-3 yr old
children than 4-7 year old
children; Cadmium detected
in maternal blood and their
children's blood (Europe);
Detected- levels varied
Associations: childhood exposure
and several bone-related
biomarkers (Bangladesh);
Childhood exposure (prenatal or
postnatal) and lower IQ in boys
and altered behavior in girls;
children's e-waste exposure and
hearing loss; dietary exposure in
children <3 yrs old and potential
nephrotoxicity effects.
Fluman and zebrafish
comparative study suggests
cadmium exposure increases
the risk of juvenile obesity.
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Acting Administrator Nishida
Page 26
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Fluman biomonitoring data2
Breastmilk Detection/Levels2
Fluman Flealth Outcome Data2
Animal Effects Data2
Chromium and
Chromium
Compounds
(category)
Industrial
TRI: Y
Hexavalent chromium present in house
dust; Applications in industries, homes
(house dust), agriculture (pesticides)
and medicine; contaminated
wastewater; found in tobacco
producing regions.
Detected in placenta; Median
urinary chromium level in
children aged 1-17 years was
0.54 iJg/g of creatinine
(Buenos Aires); Urinary
chromium concentrations
detected in children 3
months to 6 yrs old (NJ, US)
with median uncorrected
urinary chromium
concentration of 0.19 |_ig/l
(0.22+0.16).
Detected- levels varied
Associations: Gestational
exposure to chromium and fetal
growth effects; childhood
exposure and kidney injury
molecule-1; postnatal exposure
and neuropsychological
development in school-aged
children.
N/A
Cobalt and Cobalt
Compounds
(category)
Industrial
TRI: Y
Children exposure through e-waste
recycling regions, shoes, and personal
care products.
Urinary levels measured in
children >7 yrs old (Taiwan),
children had higher levels of
than adults; high urinary
levels of cobalt in workers
and people living nearby
mines or smelters (<3 km)
(DRC).
Detected- levels varied
Associations: Cobalt in footwear in
children and allergic contact
dermatitis.
N/A
Creosotes
(8001-58-9)
Industrial
TRI: Y
Creosote is a complex mixture,
containing over 200 constituents
(NIOSH, 1977); neighborhood air,
water, and soil around wood treatment
plants contaminated with wood
preserving chemicals; contaminated
groundwater from the American
Creosote Works Superfund site
(Pensacola, FL); Occupational dermal
and inhalation exposure to workers
using creosote as wood protectant to
produce railway sleepers, utility poles
and marine pilings.
PAH urinary biomarkers were
identified in soil remediation
workers (smokers and
nonsmokers) on former
creosote wood impregnation
site polluted w/creosote oil;
dermal and respiratory
exposure in creosote
workers: urinary metabolites
excretion of 1-hydroxypyrene
as good biomarkerfor PAHs.
Workers can be adolescents.
N/A
Associations: Paternal
occupational exposure and
increased odds ratios for
neuroblastoma; Potential parental
occupational exposure to creosote
and brain cancer (five cases);
Exposed residents (adults and
some children) near wood
treatment plant had significantly
more cancers and respiratory,
skin, and neurological health
outcomes than unexposed
matched controls.
Developmental toxicity (e.g.,
embryonic cardiac
deformities in Atlantic
killfish; Pacific herring
embryos near 100-yr old
creosote-treated pilings
exhibited higher Cypla gene
expression than embryos
from reference areas;
teratogenicity of
groundwater at American
Creosote Works Superfund
site, Pensacola, Fla).
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Acting Administrator Nishida
Page 27
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Fluman biomonitoring data2
Breastmilk Detection/Levels2
Fluman Flealth Outcome Data2
Animal Effects Data2
Cyanide
Compounds
(Limited to
dissociable
compounds)
(category)
Consumer;
Industrial
TRI: N
Food contaminant (e.g., cyanide in
cassava); Preterm infants in NICU often
placed in incubators that may increase
exposure to VOCs, including cyanide;
Air fresheners, aerosols, paint or
varnish, organic solvents, and
passive/active smoking (ETS)
Urinary metabolites of
cyanide higher in infants in
NICU incubators.
Detected- levels varied
Associations: Dietary cyanogen
exposure associated w/1-4 yr olds
neurodevelopmental effects
(cognitive and motor) (DRC,
Africa).
N/A
3,3'-
Dichlorobenzidine
(91-94-1)
Industrial
TRI: Y
Occupational exposure - production of
colorants.
N/A for children. Biological
monitoring of workers used
hemoglobin adducts and spot
samplings of urinary 3,3'-DBZ
excretion; urinary
mutagenicity determination
assay found that 11% of
workers (who could be
adolescents) in azo dye
manufacturing had exposure
higherthan nonworkers.
N/A
N/A for children's studies.
Mutagen.
N/A
3,3'-
Dichlorobenzidine
dihydrochloride
(612-83-9)
Consumer;
Industrial
TRI: Y
Occupational exposure - production of
colorants
N/A for children's studies.
Effective biological
monitoring was achieved
w/hemoglobin adducts and
spot samplings of urinary
3,3'-DBZ excretion in workers
(who could be adolescents),
(who could be adolescents)
N/A
N/A for children's studies.
Mutagen.
Androgen Receptor
EcoScreen assessed
androgen receptor (AR)
agonist and antagonist
activity of 253 test
compounds: identified 3,3'-
dichlorobenzidine
dihydrochloride as potent AR
antagonist.
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Acting Administrator Nishida
Page 28
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
1,2-
Dimethoxyethane
(Monoglyme)
(110-71-4)
Consumer;
Industrial
TRI: N
Occupational exposure- used as solvent
in batteries
N/A for children's studies.
Higher urinary levels of MAA
metabolite of EGdiME among
occupationally exposed
workers (who could be
adolescents) than controls.
N/A
N/A
Developmental and
Reproductive Toxicity (e.g.,
testicular atrophy,
embryotoxic effects).
2-
Dimethylaminoetha
nol (DMAE)
(108-01-0)
Industrial
TRI: N
DMAE and its salts have been used in
medicine; consumer products; related
compounds used in gas purification;
used in label printing plants
N/A
N/A
N/A for children's studies.
Associations: workers (some could
be adolescents) and blurry, halo,
and blue-grey vision.
Developmental toxicity
(DMAE inhibits choline
uptake and metabolism
during neurulation resulting
in growth retardation and
neural tube and facial
defects; increased fetal body
wt and increased incidence
of 6 skeletal variations but
no malformations).
Di-n-octyl phthalate
(DnOP) (1,2-
Benzenedica rboxyli
c acid, 1,2- dioctyl
ester)
(117-84-0)
Industrial;
Commercial;
Consumer
TRI: N
Occupational; Indoor dust; Consumer
products
MnOP detected in urine of
pregnant women; Children's
urinary MnOP not above
limits of quantification; not
identified in urine samples of
children or adolescents
(Germany); not detected in
urine from mothers and their
school-aged children in
Duisburg birth cohort study.
N/A
Associations: Urinary metabolite
of DNOP exposure in late
pregnancy and lower nonverbal IQ
scores in children; urinary
metabolites from maternal third
trimester DNOP concentration
and lower bone mineral
concentration at 10 yrs old but
associations did not remain
statistically significant after
multiple testing correction; DnOP
levels in overweight children
compared to nonoverweight.
Developmental toxicity (in
utero exposure led to
significant increase in
rudimentary lumbar ribs but
no increase in the incidence
of fetal malformations or
external and visceral
variations).
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Acting Administrator Nishida
Page 29
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Ethylbenzene
(100-41-4)
Consumer;
Industrial
TRI: Y
Air pollution as VOC (burning fossil
fuels, waste emission, coal industry);
Occupational exposures including oil
and natural gas development and
operations and composting facilities;
Indoor air contaminant; Traffic air
pollution; Tobacco smoke; Diet.
NHANES children >6 yrs old:
consuming vegetables and
fruit associated w/decreased
urinary metabolites; tobacco
smoke as a major source of
ethylbenzene exposure for
the general U.S. population;
Urine samples collected from
composting facilities workers.
Detected (Pellizzari et al. 1982)
but concentrations not reported
Associations: Pregnant women
with high exposure 5 days prior to
delivery and cardiovascular
events; Annual 2008 asthma rates
positive correlation with total
benzene, toluene, ethylbenzene
and xylene (BTEX) at 5-digit zip
code scale spatial resolution in
children (5+ yrs old) and adults
(Detroit); Children with higher
BTEX compound exposure more
likelyto receive academic support
services later in childhood (NYC).
N/A
bis(2-Ethylhexyl)
adipate (103-23-1)
Consumer;
Industrial
TRI: N
Plasticizer in food packaging (e.g.,
cereal based food, some PVC-based
plastic wrap); consumer products (e.g.,
deodorant); plastic medical devices
used in pediatric intensive care units;
and occupational exposure (e.g., DEHA
is used as hydraulic fluid, component
of aircraft lubricants).
Infants urine samples had
median dietary intake of
DEHA over 7 consecutive
days of 1.0 |jg/kg b.w. Urine
samples analyzed for DEHA
metabolites in healthy adults
was highest in those
consuming food wrapped in
cling film. Detected urinary
metabolites in pregnant
women; Healthy subjects
aged 14-60 years measured
for urinary DEHA metabolites
from food intake over 7
consecutive days - median is
0.7 (2.2) microg/kg b.w.
N/A
N/A
Reproductive toxicity e.g.,
ovarian toxicity, female
fertility); peroxisome
proliferator; Genotoxicity:
one study found no
genotoxicity in primary
cultures of adult rat
hepatocytes; Another study
found DNA damage in cells
ofzebrafish larvae.
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Acting Administrator Nishida
Page 30
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
2-Ethylhexyl
2,3,4,5-
tetrabromobenzoat
e (TBB) (183658-27-
7)
Consumer;
Industrial
TRI: N
Flame retardants and polyurethane
foams exposure occupational or in
home (indoor dust, furniture, cat hair);
children's hand wipes; Potential
through dietary intake from e waste
sites.
Detected in serum and milk
in nursing women; in hair and
fingernail samples of U.S.
college students (some
adolescents).
Detected- levels varied
N/A
Developmental toxicity (e.g.,
exposure to TBB may
activate an antioxidant
response and alter behavior
during early zebrafish
development); Endocrine
toxicity (e.g., liver gene
transcription analysis using
RNA-sequencing indicated
that 28-d dietary exposure of
trout to EH-TBB down-
regulated a gene that
mediates endocrine
processes in Rainbow trout);
Reproductive toxicity (e.g.,
fecundity effects in adult
zebrafish study).
bis(2-Ethylhexyl) -
3,4,5,6-
tetrabromophthalat
e (TBPH) (26040-
51-7)
Consumer;
Industrial
TRI: N
Flame retardants and polyurethane
foams; indoor dust (ingestion and
dermal); dust of commercial airplanes;
children's hand wipes.
Detected in maternal serum
and milk; Correlation
between fingernail levels and
dust observed; Hair and
fingernail samples analyzed
in university students,
concentrations of 20-240ng/g
in hair, <17-80ng/g in nails.
Detected- in 32.4% of milk
samples
N/A
Reproductive toxicity (e.g.,
TBPH can be metabolized by
porcine esterases to
TBMEHP and induced MNGs
in the fetal testes in a rat
model). PPAR agonist in
mouse cells. Hepatic effects.
2,5-Furandione
(108-31-6)
Industrial
TRI: Y
N/A
N/A
N/A
N/A
N/A
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Acting Administrator Nishida
Page 31
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
1-Hexadecanol
(36653-82-4)
Consumer;
Dispersive;
Industrial
TRI: N
N/A
N/A
N/A
Sparse information on children.
"Exosurf neonatal," synthetic
surfactant used to treat
respiratory distress syndrome in
newborns, assessed lung and
neuro outcomes in clinical trials:
found no adverse effects at 1 or 2
yrs old. Did not follow to later
ages.
N/A
2-Hydroxy-4-
(octyloxy)
benzophenone
(1843-05-6)
Consumer;
Commercial
TRI: N
N/A
N/A
N/A
N/A
N/A
Lead and Lead
Compounds
(category)
Consumer;
Industrial
TRI: Y
Lead-based paint in old homes and
schools (e.g., house dust); air; soil;
pellet guns; jewelry.
Detected in blood (cord and
maternal), placenta, teeth,
and urine; Numerous studies
serum levels of lead in
children (e.g., NHANES 2011).
Detected- levels varied
Associations: Developmental
neurotoxic health outcomes even
at low doses; Thyroid impacts;
Male reproductive outcomes (e.g.,
sperm quality).
Neurodevelopmental toxicity
(rats, mice, zebrafish); male
reproductive toxicity (mice);
Transgenerational effects on
brain transcriptome
(zebrafish).
Long-chain
chlorinated
paraffins (C18-20)
(category)
Industrial;
Dispersive
TRI: N
N/A
N/A
Detected- mean concentration of
19.1 (
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Acting Administrator Nishida
Page 32
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Fluman biomonitoring data2
Breastmilk Detection/Levels2
Fluman Flealth Outcome Data2
Animal Effects Data2
Medium-chain
chlorinated
paraffins (C14-17)
(category)
Consumer;
Dispersive;
Industrial
TRI: N
Food, dust; in adhesives; plastic sports
courts and synthetic turf; indoor air
environments (e.g., residential houses,
malls, offices, and student
dormitories); Indoor dust and indoor
air posed high risks fortoddlers and
infants.
Lactational transfer. Study of
short and medium chain CPs
found levels of both JSCCP
and JMCCP were present in:
maternal serum > breast milk
> cord serum > placenta.
Detected- levels varied
N/A
N/A
4,4'-Methylene
bis(2- chloroaniline)
(101-14-4)
Consumer;
Industrial
TRI: Y
Occupational exposure: polyurethane
workers; plastic product manufacture.
N/A for children's studies.
Case report of accidental spill
resulting in dermal exposure
to worker: serial urinary
MBOCA samples from the
worker over a 2 week period
allowed calculation of
biological half-life for MBOCA
in urine of approximately 23
hours.
N/A
No human data; suspected human
carcinogen
No info on dev and repro
tox; known animal
carcinogen
Molybdenum and
Molybdenum
Compounds
(category)
Consumer;
Industrial
TRI: N
Mining and living near mining areas;
personal care products (e.g., colored
cosmetics); diet (e.g., vegetables);
cobalt-chromium-molybdenum
(CoCrMo) metal-on-metal prosthetics.
Detected in urine, amniotic
fluid, cord blood, pregnant
women maternal serum,
children's nails, and placenta;
Mo concentration in urine
was 52.1+/-29.3 microg/Lfor
children living near mine
(Mexico). Children who ate
more vegetables had higher
levels Mo (NHANES; Spain)
Detected- levels varied
Associations: higher Mo in
umbilical cord and higher risk for
cleft lip or cleft palate; higher
urinary Mo level in children and
DNA and lipid damage;
Concentrations above the median
and increased risk for NTDs.
N/A
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Acting Administrator Nishida
Page 33
January 26, 2021
Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Naphthalene
(91-20-3)
Consumer;
Industrial
TRI: Y
Incomplete combustion of organic
materials; traffic emissions; smoked or
barbecued food; leafy vegetables;
mothballs; indoor air (e.g., tobacco
smoke); crabs of polluted waters; gas
stations and gas filler occupational
exposure.
Metabolites detected in
urine, serum, breast milk;
Urinary metabolites: 3 yr olds
with hydroxynaphthalenes
predominant (Poland);
higher levels in adolescents
and adults than young
children (Australia);
preschool air levels and
children's urinary levels
correlate; high metabolite
levels in mothers and their
newborns (Czech Republic).
Detected- levels varied
Poisoning incidents of children
from mothballs leads to acute
intravascular hemolysis leading to
anemia, hemoglobinuria,
methemoglobinemia, and acute
kidney injury (AKI); Associations:
Highest napthalene metabolite in
urine and increased risk of obesity
in children (Canada); Maternal air
emission exposure and low birth
weight in offspring; prenatal
exposure and adverse brain
development (Taiwan). Serum
metabolite levels and asthma
biomarkers in children.
Developmental toxicity
(juveniles exposed to NA
induced lung cytotoxicity
[mice]; increased rates of
embryonic mortality and
malformation, and
decreased hatchability
[zebrafish]); Developmental
neurotoxicity in PAH mixture
study including napthalene
(zebrafish).
2-
Naphthalenecarbox
ylic acid, 4-[(4-
chloro-5- methyl-2-
sulfophenyl) azo]-3-
hydroxy-, calcium
salt (1:1) (Pigment
Red 52) (
17852-99-2)
Consumer;
Industrial
TRI: N
N/A
N/A
N/A
N/A
N/A
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Nickel and Nickel
Compounds
(category)
Consumer;
Industrial
TRI: Y
Consumer products (e.g., jewelry,
coins, zippers, belts, tools, toys, chair
studs, cases for cell phones and
tablets); dental appliances;
Contamination of air, food, and water;
naturally occurring in rock and soil;
Occupational exposure and fence-line
communities (e.g., mining; oil
refineries; non-ferrous metal plants.
Detected in serum, urine, and
hair of children.
Detected- levels varied
Associations: Allergic contact
dermatitis (ACD) in children; most
frequent cause of contact allergy
worldwide; higher maternal
urinary nickel and increased risk
of preterm delivery; maternal
levels and congenital heart
defects in offspring; in utero levels
and slower progression of breast
development in offspring; Ni
levels negatively associated with
testosterone in girls 8-13 yrs old.
Developmental toxicity (e.g.,
embryonic effects [sea
urchin])
N-
Nitrosodiphenylami
ne
(86-30-6)
Consumer;
Industrial
TRI: Y
N/A
N/A
N/A
N/A
Cytotoxicity in hamster ovary
cells; Carcinogen
Nonylphenol and
Nonylphenol
Ethoxylates
(NP/NPEs)
(category)
Commercial;
Industrial
TRI: Y
Consumer products; food (grains,
livestock, and seafood); industrial
applications; soil.
Detected in serum, urine,
cord blood in children.
Detected- levels varied
Associations: ADHD in children 4-
15 yrs old; maternal 4-n-
nonylphenol exposure and
spontaneous abortion
Developmental neurotoxicity
(e.g., CNS molecular
changes after in utero
exposure, involved in
RXRa/PXR/CAR signaling
pathways [mouse primary
neuronal cell cultures]; NP
developmental exposure
leads to hyperadrenalism
[rat]); Reproductive toxicity
(4-Nonylphenol effects on
rat testis; Transcriptomic
analysis found genes in gene
ontologies related to germ
cell development and
reproduction).
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
4-tert-Octylphenol
(4-(l,1,3,3-
Tetramethylbutyl)-
phenol) (140-66-9)
Consumer;
Industrial
TRI: N
Industrial chemicals used in the
manufacture of nonionic surfactants
(top)
Urine levels of tOP: young
children had higher
concentrations than
adolescents; and adolescents
higher concentrations than
adults (NHANES).
Detected- levels varied
Associations: Significant negative
associations between maternal
urinarytOP concentrations and
neonatal sizes at birth (males
more sensitive than females).
Endocrine disruptor (e.g.,
decrease in circulating
thyroxine, increase in thyroid
follicular cell hypertrophy,
hyperplasia during
metamorphosis and
Mullerian duct development
effects [frogs]; some males
exhibit testicular oocytes
[fish]; estrogen action
increased the percentage
primordial and developing
follicles and cell proliferation
in neonatal ovaries [pigs];
positive correlation with
feminization indicators in
males and masculinization
indicators in females [fish]).
Octamethylcyclotet
rasiloxane (D4)
(556-67-2)
Consumer-
Dispersive;
Industrial
TRI: N
Consumer products (e.g., personal care
products); indoor air: infants had
highest levels and adults had lowest
levels of D4; medical devices (e.g.,
breast implants).
Detected in serum of
pregnant women.
N/A
N/A
Female reproductive toxicity
(delays ovulation by delay of
LH surge; estrogenic and
antiestrogenic activity;
dopamine agonist-like
activity; 2-gen reproductive
study found female effects
on fertility and litter size;
acceleration of onset of
female reproductive
senescence (rat).
P,P'-
Oxybis(benzenesulf
onyl hydrazide)
(80-51-3)
Consumer
TRI: N
N/A
N/A
N/A
N/A
N/A
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Fluman biomonitoring data2
Breastmilk Detection/Levels2
Fluman Flealth Outcome Data2
Animal Effects Data2
Styrene
(100-42-5)
Consumer;
Industrial
TRI: Y
Plastics manufacturing; Food (e.g.,
migration from polystyrene-based food
packaging; consumer products (e.g., air
fresheners, aerosols, paint/varnish,
organic solvents, scented products);
formation during the biodegradation of
a wide variety of naturally occurring
compounds with structures similarto
styrene; Air exposure (e.g., tobacco
smoke is major route).
Individuals with high
vegetable and fruit intake
had lower urinary metabolite
levels (NHANES , >6 years
old); detected in pregnant
women urine and higher in
smokers; urinary metabolites
of children 6-11 yrs old
decreased with age and
overall, children had higher
levels than nonsmoking
adults (NHANES).
Detected- median value of 0.129
ng mL(-l) (also detected in
Pellizzari et al. 1982 and modeled
in Fisher et al. 1997)
Associations: Childhood obesity;
low birth weight in offspring
(Texas); in utero exposure and
increased risk of ASD (PA; NATA
data); Birth cohort of premature
children and children with allergic
risk factors - Fligher styrene levels
in home associated with increased
risk of pulmonary infections in six-
week-old infants (LARS)
Developmental toxicity
(embryotoxic
[Mediterranean mussel];
polystyrene nanoparticle
studies found decreased
heart rate and altered larval
behavior (Zebrafish), delayed
gonad maturation and
decreased fecundity of
female and decreased the
hatching rate, heart rate,
and body length of offspring
[Medaka]; and no effects on
growth or swimming activity
[frog tadpoles]).
Tribromomethane
(Bromoform)
(75-25-2)
Consumer;
Industrial
TRI: Y
Air toxic; Water disinfection byproduct
(product of chlorination); Children
exposure via showering, bathing,
swimming, and drinking water.
Maternal blood bromoform
(TBM) detected in pregnant
women.
N/A
Associations: perinatal exposure
to bromoform and ASD diagnosis;
in utero exposure may be
associated with impaired neonatal
neurobehavioral development of
offspring; blood levels of total
trihalomethanes during late
pregnancy and lower mean birth
weight of offspring.
Developmental toxicity
(embryo-larval
developmental toxicity [sea
urchin]); cytotoxicity;
genotoxicity; and
mutagenicity.
Triglycidyl
isocyanurate (2451-
62-9)
Consumer;
Industrial
TRI: N
Epoxy derivative, mainly in polyester
powder paints; occupational air
exposure; no children's exposure
studies identified.
N/A
N/A
N/A for children's health outcome
studies; Studies of workers (which
can include adolescents),
exposure associated with allergic
contact dermatitis and asthma.
N/A
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Vinyl chloride
(75-01-4)
Consumer;
Industrial
TRI: N
Petrochemical occupational exposure
and proximity to complex; indoor
environmental tobacco smoke;
polyvinyl chloride (PVC) in children's
products (play mats, etc.); NJ vinyl
chloride release incident (2012).
Urinary metabolite studies:
thiodiglycolic acid (TDGA),
potential vinyl chloride
monomer (VCM) biomarker,
measured in children living
near petrochemical complex;
vinyl chloride metabolites
identified in pregnant
women; detected in children
6-11 yrs old (NHANES);
metabolites of VOC in
neonates in intensive care
units at 2X levels reported for
children in NHANES.
N/A
Associations: Studies in workers
(some of whom may be
adolescents): liver effects;
Children with higher urinary TDGA
levels had associations with
hepatic function and fibrosis index
and increased risk of pediatric
non-alcoholic fatty liver disease
(NAFLD); pregnancy drinking
water contaminants, including
vinyl chloride, and neural tube
defects in children (Camp
LeJeune).
Genotoxicity; Developmental
toxicity differed by route of
exposure: No effects
observed on embryonic or
fetal development after
inhaled vinyl chloride
monomer (mouse, rat and
rabbit) vs. injection during
early pregnancy increased
incidence of malformations,
esp. NTDs in embryos (mice).
m-Xylene
(108-38-3)
Consumer;
Industrial
TRI: Y
Outdoor air (e.g., traffic); Indoor air
(cooking/cleaning, childcare facilities,
smoking, higher levels in houses with
attached garage); consumer products;
occupational exposure; municipal solid
waste composting facility; drinking
water.
Urine concentration
measured in municipal solid
waste composting facility
workers (can be adolescents
or adults) for m-/p-/o-
xylene; Blood concentrations
of m-/p-/o- xylene measured
in children (Mn; 150 children
from two low income,
minority city neighborhoods);
N/A
Associations: High pregnancy
exposure and cardiovascular
events in pregnant woman;
Interaction between asthma and
air exposure to m-/p-/o- xylene in
pregnant women increased risk of
preeclampsia; indoor air levels
and nasal obstruction in children;
o-xylene exposure during
pregnancy and occurrence of
wheezing symptoms in infant;
N/A for developmental or
reproductive studies;
cytotoxicity
o-Xylene
(95-47-6)
Consumer;
Industrial
TRI: Y
Detected- median value of 0.159
ng mL(-l)
No rodent developmental or
reproductive toxicity studies
identified; embryonic growth
and development effects
found in ecological toxicity
study (marsh frog).
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
p-Xylene
(106-42-3)
Consumer;
Industrial
TRI: Y
blood levels in children
(NHANES)
Detected- median value of 0.539
ng mL(-l)
among children with asthma m,p-
xylene, or o-xylene exposure
associated with asthma
symptoms; xylene exposure may
contribute to risk of allergic
sensitization to food allergens
milk and egg white (LARS);
Primary school children residing
near oil terminal with VOC
exposure - exposure to o-xylene
and respiratory symptoms.
One dev study identified:
Prenatal exposure to p-
xylene and no effects noted
(rat)
Ethanone, 1-
(1,2,3,4,5,6,7,8-
octahydro-2,3,5,5-
tetramethyl-2-
naphthalenyl)
(54464-59-4)
Consumer;
Industrial
TRI: N
In fragrances; personal care products;
Detection in the environment (e.g.,
sludge, wastewater, river water, and
house dust samples)
N/A
N/A
N/A
Sparse data. Gavage study in
rats: Fetal body weights
were reduced by 480
mg/kg/d, but not to a
statistically significant
degree.
Ethanone, 1-
(1,2,3,4,5,6,7,8-
octahydro-2,3,8,8-
tetramethyl-2-
naphthalenyl)
(54464-57-2)
Consumer-
Industrial
TRI: N
In fragrances; personal care products;
Detection in the environment (e.g.,
sludge, wastewater, river water, and
house dust samples)
N/A
Detected- in 34% of breast milk
samples; median concentration
value <1.5 ng/g lipid
N/A
Sparse data. Gavage study in
rats: Fetal body weights
were reduced by 480
mg/kg/d, but not to a
statistically significant
degree.
Ethanone, 1-
(l,2,3,4,6,7,8,8aoct
ahydro- 2,3,8,8-
tetramethyl-2-
naphthalenyl)
(68155-67-9)
Consumer-
Industrial
TRI: N
In fragrances; personal care products;
Detection in the environment (e.g.,
sludge, wastewater, river water, and
house dust samples)
N/A
N/A
N/A
Sparse data. Gavage study in
rats: Fetal body weights
were reduced by 480
mg/kg/d, but not to a
statistically significant
degree.
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Chemical Name
(CAS) and Use1
Found on Toxics
Release Inventory
(TRI): Y/N
CEH Exposure
CEH Effects
Exposure information2
Human biomonitoring data2
Breastmilk Detection/Levels2
Human Health Outcome Data2
Animal Effects Data2
Ethanone, 1-
(l,2,3,5,6,7,8,8aoct
ahydro- 2,3,8,8-
tetramethyl-2-
naphthalenyl)
(68155-66-8)
Consumer-
Industrial
TRI: N
In fragrances; personal care products;
Detection in the environment (e.g.,
sludge, wastewater, river water, and
house dust samples)
N/A
N/A
N/A
Sparse data. Gavage study in
rats: Fetal body weights
were reduced by 480
mg/kg/d, but not to a
statistically significant
degree.
information from the 2014 TSCA Workplan: https://www.epa.gov/sites/production/files/201501/documents/tsca work plan chemicals 2014 update-
final.pdf
2 OCHP Staff performed searches for literature in PubMed in July 2020. Children's exposure search terms: children AND ( OR )
AND exposure; children's biomonitoring search terms: children AND ( OR ) AND biomonitoring; Children's human health
outcome search terms: (Children OR Develop*) AND Human Health Outcome (Data OR study) AND ( OR ); Children's relevant
effects: (Children OR Develop*) AND Animal Effect (Data OR study) AND ( OR ); Breast milk search terms: (human milk OR
breast milk) AND ( OR ).
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Attachment D: Example GIS Analysis
Here we present examples of GIS analysis illustrating our recommendations for charge question 1. These
examples are not mutually exclusive and can be combined with each other and/or with other relevant data
sources to inform prioritization and risk evaluation by providing a more detailed and informative picture of
social and environmental factors that affect susceptibility and vulnerability.
Data Sources and Method
Toxics Release Inventory (TRI): 2016 TRI data on air, water and land releases reported for benzene or
ethylbenzene were aggregated to the county level, summing the release data wherever more than one
facility reported releases in a county.
Social Vulnerability Index (SVI): 2016 county level data for population and overall SVI were used.
National Air Toxics Assessment (NATA): 2014 cancer risk data were aggregated to the county level,
averaging the cancer risk data of the census tracts that make up each county. NATA data from Excel files
were merged with shapefiles of counties by FIPS code.
NATA cancer risk values are calculated by the EPA based on emissions data and modeling for all carcinogenic
Hazardous Air Pollutants (HAPs). For the TSCA Workplan chemicals, we recommend analyzing co-exposures
with HAPs that affect the relevant related health endpoint(s). NATA estimates include total respiratory
hazard indexes as well as other endpoints relevant for children's health.
On request of the CHPAC TSCA Workgroup, ICF created the bivariate choropleth maps included here. More
information about the maps and visual analysis is available upon request.
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Map: Benzene TRI data and SVI
Benzene and Social Vulnerability
2016 Toxics Release Inventory (TRI) Program, 2016 CDC Social Vulnerability Index,Esri, Esri, HERE
Population
Benzene Releases (Low to High)
Benzene Releasing Facilities
Social Vulnerability
¦ Benzene Releases
Counties with highest Social Vulnerability Index and highest benzene releases are indicated by the darkest
color. Table contains summed population numbers for each combination of exposure and SVI.
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Map: Ethylbenzene TRI data and SVI
Ethylbenzene and Social Vulnerability
Population
38,873,108
23,936,784
46,996,945
Ethylbenzene Releases (Low to High)
2016 Toxics Release Inventory (TRI) Program, 2016 CDC Social Vulnerability Index,Esri, Esri, HERE
Ethylbenzene Releases
High I
Ethylbenzene Releasing Facilities
¦I Social Vulnerability
Counties with highest Social Vulnerability Index and highest ethylbenzene releases are indicated by the
darkest color. Table contains summed population numbers for each combination of exposure and SVI.
This information could be used in a variety of ways to inform prioritization. For example, EPA can identify
counties with both high volume of TRI releases and high social vulnerability for each remaining chemical on
the workplan (high/ high counties), and also quantify the number of people in such counties by summing
high/high county population estimates for each chemical. The number of people in high/high counties can
then be compared for each chemical to help direct prioritization. Different chemicals can be compared to
each other and used to identify where multiple exposures may be occurring to the same vulnerable
population. Potential co-exposures could also be evaluated by considering TRI releases in combination with
other types of environmental exposures, such as hazardous air pollutants as in the following example.
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Map: Benzene TRI data and NATA total cancer risk
Counties with highest total cancer risk due to Hazardous Air Pollutant emissions and highest benzene
releases are indicated by the darkest color. Table contains summed population numbers for each
combination of exposure and cancer risk.
The example presented in this map shows NATA total cancer risk as a general example. CHPAC notes that
consideration of co-exposures should be focused on chemicals that affect related health endpoints, such as
affecting the same body system or association with increased risk of related types of cancer.
Additionally, this type of analysis could be performed for any of the critical health endpoints highlighted in
the letter:
• Reproductive toxicity
• Developmental toxicity (including developmental neurotoxicity)
• Endocrine toxicity, including metabolism disrupting chemicals
• Respiratory toxicity and potential effects on lung development, structure or function
• Toxicity to the immune system, including immunosuppression and excessive activation
• Toxicity that through preconception and/or in-utero exposures
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Attachment E: Resources for social vulnerability and environmental co-exposure information
Resource
Type of information
Agency/ Source
National
Superfund National Priorities List
sites
Environmental co-exposures
US EPA
Toxics Release Inventory
Environmental co-exposures
US EPA
Methods for modeling TRI
emissions at different levels of
geographic resolution
Environmental co-exposures
Dolinoy, D. C., & Miranda, M. L.
(2004). GIS modeling of air toxics
releases from TRI-reporting and
non-TRI-reporting facilities:
Impacts for environmental justice.
Environmental Health
Perspectives, 112(17), 1717-1724.
https://doi.org/10.1289/ehp.7066
National Health and Nutrition
Examination Survey (NHANES)
Environmental co-exposures
and social vulnerability
Centers for Disease Control and
Prevention (CDC)
National Air Toxics Assessment
Environmental co-exposures
US EPA
EJ Screen
Environmental co-exposures
and social vulnerability
US EPA
National Toxic Substance
Incidents Program (NTSIP)
Environmental co-exposures
Agency for Toxic Substances and
Disease Registry (ATSDR)
American Community Survey
Population characteristics
and demographics
US Census Bureau
US census data
Population characteristics
and demographics
US Census Bureau
National Electronic Injury
Surveillance System (NEISS)
Chemical co-exposures
Consumer Product Safety
Commission (CPSC)
National Poison Data System
Chemical co-exposures
American Association of Poison
Control Centers
Household Products Database
Chemical co-exposures
National Institutes of Health
Social Vulnerability Index
Social vulnerability
Centers for Disease Control and
Prevention (CDC)
National Environmental Public
Health Tracking
Environmental co-exposures
and social vulnerability
Centers for Disease Control and
Prevention (CDC)
Facility Registry Service (FRS)
Environmental co-exposures
US EPA
Product testing data
Chemical co-exposures
Washington State Department of
Ecology
High Priority Chemicals Data
System (HPCDS)
Chemical co-exposures
Interstate Chemicals
Clearinghouse
County Health Rankings
Population health metrics
University of Wisconsin/ Robert
Wood Johnson Foundation
Contaminant Occurrence and
Related Data for Six-Year Review
of Drinking Water Standards
Chemical co-exposures
US EPA
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Resource
Type of information
Agency/ Source
America's Children Report
Environmental co-exposures
and social vulnerability
Federal Interagency Forum on
Child and Family Statistics
America's Children and the
Environment Report
Environmental co-exposures
US EPA
EnviroAtlas
Environmental co-exposures
US EPA
State/ Local
CalEnviroScreen
Environmental co-exposures
and social vulnerability
California EPA
California Pesticide Use
Reporting (PUR)
Environmental co-exposures
California EPA
California air toxics monitoring
information
Environmental co-exposures
California Air Resources Board
Washington state social
vulnerability mapping
Environmental co-exposures
and social vulnerability
Washington Department of
Health
Washington state lead and
arsenic smelter data
Environmental co-exposures
Washington Department of
Ecology
Washington state Toxics Clean
Up Program
Environmental co-exposures
Washington Department of
Ecology
Minnesota Areas of
Environmental Justice Concern
GIS-based screening tool
Environmental co-exposures
and social vulnerability
Minnesota Pollution Control
Agency
New York state Maps &
Geospatial Information System
(GIS) Tools for Environmental
Justice
Social vulnerability
New York Department of
Environmental Conservation
New York City Environment and
Health Data Portal
Environmental co-exposures
and social vulnerability
NYC Department of Health and
Mental Hygiene
State Environmental Public
Health Tracking Programs (25
states, funded by CDC)
Environmental co-exposures
and social vulnerability
Specific to state
City Health Dashboard
Environmental co-exposures
and social vulnerability
New York University/ Robert
Wood Johnson Foundation
State Biomonitoring Programs
Environmental co-exposures
Specific to state; Association of
public health laboratories has a
current list
Protecting the health of children:
National snapshot of
environmental health services
Environmental co-exposures
and social vulnerability
American Public Health
Association
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Resource
Type of Information
Agency/ Source
Tribal
Great Lakes region
Environmental co-exposures
Great Lakes Indian
Fish & Wildlife Commission
National
Environmental co-exposures
Northern Arizona University
Institute for Tribal Environmental
Professionals
National- Environmental
Environmental co-exposures
EPA
Protection in Indian Country
National
Environmental co-exposures
Tribal Court Clearinghouse for
Environmental Resources
Native American Lands
Environmental co-exposures
Department of Defense
Environmental Mitigation
Program
Longitudinal children's health studies
Environmental Influences on
Environmental co-exposures
National Institutes of Health
Child Health Outcomes (ECHO)
and social vulnerability
program, bringing together
about 70 existing cohorts of
children, with aim to enroll
50,000 participants
Project VIVA
Environmental co-exposures
and social vulnerability
Harvard Medical School
Center for the Health
Environmental co-exposures
UC Berkeley
Assessment of Mothers and
and social vulnerability
Children of Salinas (CHAMACOS)
Study
Columbia Center for Children's
Environmental co-exposures
Columbia University
Environmental Health
and social vulnerability
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Attachment F: Chemicals not on TSCA Workplan to consider for prioritization
This is a list of chemicals entering Step 2 of 2012 TSCA workplan process that were potential candidates for
information gathering or that did not meet scoring criteria for inclusion on 2012 or 2014 Workplan.
Source: To generate the list of 267 chemicals presented here, we started with the table of 345 chemicals in
this document: US EPA, TSCA Work Plan: 2012 Scoring of Potential Candidate Chemicals Entering Step 2.7 We
then removed the chemicals that were included on the 2014 TSCA Workplan from the table.
An Excel file of this attachment is available upon request.
2012
Hazard
Score
2012
Exposure
Score
2012
Chemical Name
CASRN
Persistence/
Bioaccumulation
Score
(l,l-Dimethylethyl)-4-methoxyphenol
25013-16-5
3
2
1
(13Z)-Docosenamide
112-84-5
1
3
1
(l-Methylethenyl)benzene
98-83-9
3
2
1
(Chloromethyl) benzene
100-44-7
3
2
1
(Dichloromethyl)benzene
98-87-3
3
1
1
(Z)-l,2-Dichloroethylene
156-59-2
1
3
[l,l'-Biphenyl]-4,4'-diamine
92-87-5
3
1
1
[l,l'-Biphenyl]-4,4'-diamine, 3,3'-dimethyl-
119-93-7
3
2
1
[l,l'-Biphenyl]-4-amine
92-67-1
3
1
1
l-(l,l-Dimethylethyl)-3,4,5-trimethyl-2,6-
dinitrobenzene
145-39-1
3
3
2
l-(2-Phenyldiazenyl)-2-naphthalenol
842-07-9
3
*
2
1,1,1,2,2,2-Hexachloroethane
67-72-1
2
1
2
l,l,l,3,3,3-Hexafluoro-2-propanone
684-16-2
3
1
2
1,1,1-Trichloroethane
71-55-6
2
2
2
1,1,2,2-Tetrachloroethane
79-34-5
3
1
2
l,l'-Oxybis[l-chloromethane]
542-88-1
3
1
1
1,2,3-Propanetricarboxylic acid, 2-
(acetyloxy)-, 1,2,3-tributyl ester
77-90-7
2
2
1
1,2,3-Propanetricarboxylic acid, 2-hydroxy-
,lithium salt (1:3)
919-16-4
2
*
*
1,2,3-Propanetricarboxylic acid, 2-hydroxy-
,potassium salt (1:3)
866-84-2
2
3
1
1,2,3-Propanetricarboxylic acid, 2-hydroxy-
,sodium salt (1:3)
68-04-2
1
3
1
7 Available: https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-2012-scoring-
potential-candidate
-------
Acting Administrator Nishida
Page 48
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
1,2,3-Propanetriol, 1,2,3-triacetate
102-76-1
2
2
1
1,2,3-Trichloropropane
96-18-4
3
1
2
1,2,4,5-Tetrachlorobenzene
95-94-3
3
1
3
1,2,4-Benzenetricarboxylic acid, l,2,4-tris(2-
ethylhexyl) ester
3319-31-1
2
3
1
1,2,4-Benzenetricarboxylic acid, mixed
branched tridecyl and isodecyl esters
70225-05-7
3
*
1
1,2-Benzenedicarboxylic acid, 1,2-diethyl
ester
84-66-2
1
3
1
1,2-Benzenedicarboxylic acid, 1,2-diheptyl
ester, branched and linear
68515-44-6
3
2
1
1,2-Benzenedicarboxylic acid, 1,2-
dimethylester
131-11-3
2
3
1
1,2-Benzenedicarboxylic acid, 1,2-
diundecylester, branched and linear
85507-79-5
1
3
1
1,2-Benzenedicarboxylic acid, 1-heptyl 2-
nonyl ester, branched and linear
111381-89-6
1
2
1
1,2-Benzenedicarboxylic acid, 1-heptyl 2-
undecyl ester, branched and linear
111381-90-9
1
2
1
1,2-Benzenedicarboxylic acid, 1-nonyl 2-
undecyl ester, branched and linear
111381-91-0
1
2
1
1,2-Benzenedicarboxylic acid, di-C6-14-
branched and linear alkyl esters
309934-69-8
1
3
2
1,2-Ethanediol
107-21-1
1
2
1
l,3,5-Triazine-2,4,6(lH,3H,5H)-trionel,3,5-
tris[[4-(l,l-dimethylethyl)-3-hydroxy-2,6-
dimethylphenyl]methyl]-
40601-76-1
1
3
2
1,3,5-Tribromobenzene
626-39-1
3
1
2
1,3-Benzenediamine, 4-methyl-
95-80-7
3
1
1
1,3-Dichloro-l-propene
542-75-6
3
2
1
1,3-Dichlorobenzene
541-73-1
2
2
2
1,3-Dinitrobenzene
99-65-0
1
1
2
1,3-Dioxolane
646-06-0
2
3
*
1,4-Benzenedicarboxylic acid, 2,5-
bis(phenylamino)-
10109-95-2
*
2
1
-------
Acting Administrator Nishida
Page 49
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
1,4-Benzenedicarboxylic acid, 2,5-bis[(4-
methylphenyl)amino]-
10291-28-8
*
2
2
1,4-Dinitrobenzene
100-25-4
3
1
2
l,4-Dioxacyclohexadecane-5,16-dione
54982-83-1
2
3
1
l,6-Octadien-3-ol, 3,7-dimethyl-
78-70-6
1
3
1
l,8-Dihydroxy-4-nitro-5-(phenylamino)-9,10-
anthracenedione
20241-76-3
3
2
2
l-[2-(2,4-Dinitrophenyl)diazenyl]-2-
naphthalenol
3468-63-1
3
2
2
l-[2-(2-Chloro-4-nitrophenyl)diazenyl]-2-
naphthalenol
2814-77-9
3
2
2
l-[2-(4-Methyl-2-nitrophenyl)diazenyl]-2-
naphthalenol
2425-85-6
3
2
2
1-Butanol
71-36-3
2
3
1
1-Decanaminium, N-decyl-N,N-dimethyl-,
1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
heptadecafluoro-l-octanesulfonate (1:1)
251099-16-8
*
*
3
1-Decanol
112-30-1
1
3
1
1-Dodecanol
112-53-8
1
3
1
1-Eicosanol
629-96-9
1
3
2
lH-Benz[de]isoquinoline-l,3(2H)-dione
81-83-4
*
3
1
1-Hexanol
111-27-3
1
3
1
l-Methoxy-4-[(lE)-l-propen-l-yl] benzene
4180-23-8
2
3
1
l-Methyl-2,4-dinitrobenzene
121-14-2
3
1
2
l-Methyl-2-nitrobenzene
88-72-2
3
1
1
1-Naphthalenemethanol, .alpha.,.alpha.-
bis[4- (diethylamino)phenyl]-4-(ethylamino)-
1325-86-6
*
*
3
1-Naphthalenemethanol, .alpha.,.alpha.-
bis[4- (dimethylamino)phenyl]-4-
(phenylamino)-
6786-83-0
*
2
3
1-Naphthalenemethanol, a,a-bis[4-
(dimethylamino) phenyl]-4-
(methylphenylamino)-
1325-85-5
3
*
2
1-Naphthalenesulfonic acid, 2-[2-(2-hydroxy-
l-naphthalenyl)diazenyl]-, barium salt (2:1)
1103-38-4
1
3
2
-------
Acting Administrator Nishida
Page 50
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
1-Naphthalenesulfonic acid, 2-[2-(2-hydroxy-
l-naphthalenyl)diazenyl]-, calcium salt (2:1)
1103-39-5
*
3
2
1-Octadecanol
112-92-5
1
3
2
1-Octanol
111-87-5
3
3
1
1-Propanol
71-23-8
2
2
1
1-Tetradecanol
112-72-1
1
3
1
2-(l,3-Dihydro-3-oxo-2H-indol-2-ylidene)-
l,2-dihydro-3H-indol-3-one
482-89-3
3
3
1
2-(Butoxymethyl)oxirane
2426-08-6
2
3
1
2-(Chloromethyl)-oxirane (Epichlorohydrin)
106-89-8
3
2
1
2-(Phenoxymethyl)oxirane
122-60-1
2
2
1
2,2,3,3,4,4,5,5,6,6,7,7,7-
Tridecafluoroheptanoic acid
375-85-9
*
*
3
2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12
,12,12-Tricosafluorododecanoic acid
307-55-1
1
2
3
2,2'-[(3,3'-Dichloro[l,l'-biphenyl]-4,4'-
diyl)bis(2,l-diazenediyl)]bis[3-oxo-N-
phenylbutanamide
6358-85-6
1
3
2
2,2'-[(3,3'-Dichloro[l,l'-biphenyl]-4,4'-
diyl)bis(2,l-diazenediyl)]bis[N-(2,4-
dimethylphenyl)-3-oxobutanamide
5102-83-0
1
3
2
2,2'-[Oxybis(methylene)]bisoxirane
2238-07-5
3
*
1
2,2-Dichloroacetic acid
79-43-6
3
3
1
2,3,4,5,6-Pentabromophenol
608-71-9
3
2
2
2,3-Dibromo-l-propanol phosphate
126-72-7
3
2
2
2,3-Dihydro-l,l,3,3,5-pentamethyl-4,6-
dinitro-lH-indene
116-66-5
3
*
2
2,4-Dichlorophenol
120-83-2
3
1
2
2,4-Pentanedione
123-54-6
3
3
1
2,5-Dichlorophenol
583-78-8
1
2
2
2,5-Dimethylfuran
625-86-5
1
3
1
2,6-Dimethyl-2-octanol
18479-57-7
*
3
1
2-[(2-Propen-l-yloxy)methyl]-oxirane
106-92-3
2
2
1
2-[2-(2-Methoxy-4-nitrophenyl)diazenyl]-N-
(2-methoxyphenyl)-3-oxobutanamide
6358-31-2
1
3
2
2-[3-(3-Chlorophenyl) propyl] pyridine
101200-53-7
*
*
2
-------
Acting Administrator Nishida
Page 51
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
2-[4,6-Bis(2,4-dimethylphenyl)-l,3,5-triazin-
2-yl]-5-(octyloxy) phenol
2725-22-6
1
2
2
2-Bromopropane
75-26-3
2
1
1
2-Butanone
78-93-3
1
3
1
2-Buten-l-ol, 2-ethyl-4-(2,2,3-trimethyl-3-
cyclopenten-l-yl)-
28219-61-6
3
3
2
2-Butenedioic acid (2Z)-, l,4-bis(2-
ethylhexyl)ester
142-16-5
3
3
1
2-Chloro-6-(trichloromethyl)pyridine
1929-82-4
2
2
2
2-Chlorophenol
95-57-8
3
1
1
2-Chloropropanoic acid
598-78-7
3
*
1
2-Ethoxy-2-methylpropane
637-92-3
1
2
1
2-Ethoxyethane
110-80-5
1
3
1
2-Ethoxyethyl acetate
111-15-9
3
2
1
2-Ethylhexanoic acid
149-57-5
1
3
1
2-Hexanone
591-78-6
2
1
1
2-Methoxy-2-methylpropane
1634-04-4
1
3
1
2-Methoxyethanol
109-86-4
2
2
1
2-Methoxyethyl acetate
110-49-6
3
1
1
2-Methyl-l,3-dinitrobenzene
606-20-2
1
1
2-Methylbenzylamine
95-53-4
3
1
1
2-Naphthalenecarboxylic acid, 3-hydroxy-
92-70-6
2
2
1
2-Naphthalenecarboxylic acid, 3-hydroxy-4-
[2-(4-methyl-2-sulfophenyl)diazenyl]-,
calcium salt (1:1)
5281-04-9
2
3
2
2-Naphthalenecarboxylic acid, 4-[2-(5-
chloro- 4-methyl-2-sulfophenyl)diazenyl]-3-
hydroxy-, calcium salt (1:1)
7023-61-2
1
3
2
2-Naphthalenol, l-[2-(2,4-
dimethylphenyl)diazenyl]-
3118-97-6
1
2
3
2-Naphthalenol, l-[2-(2-
methoxyphenyl)diazenyl]-
1229-55-6
2
*
2
2-Naphthylamine
91-59-8
3
*
2
2-Oxetanone
57-57-8
3
2
1
2-Oxiranemethanol
556-52-5
3
1
1
2-Phenyloxirane
96-09-3
3
1
1
-------
Acting Administrator Nishida
Page 52
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
2-Propanone
67-64-1
1
3
1
2-Propenamide
79-06-1
3
2
1
2-Propenoic acid, 3-(4-methoxyphenyl)-, 2-
ethylhexyl ester
5466-77-3
1
3
1
2-Propenoic acid, butyl ester
141-32-2
2
2
1
3-(2-Oxiranyl)-7-oxabicyclo[4.1.0] heptane
106-87-6
2
*
1
3,7-Dimethyl-6-octen-l-ol
106-22-9
2
3
1
3-Chloro-l-propene
107-05-1
3
2
1
3-Methylphenol
108-39-4
3
2
1
3-Oxo-N-phenylbutanamide
102-01-2
2
2
1
4-(4-Hydroxy-4-methylpentyl)-3-
cyclohexene-l-carboxaldehyde
31906-04-4
2
3
1
4,4'-(l,l-Dioxido-3H-2,l-benzoxathiol-3-
ylidene)bis[2,5-dimethylphenol]
125-31-5
3
*
2
4,4'-(l,l-Dioxido-3H-2,l-benzoxathiol-3-
ylidene)bis[2,6-dibromophenol]
115-39-9
1
*
3
4,4'-(l,l-Dioxido-3H-2,l-benzoxathiol-3-
ylidene)bis[2-bromo-6-methylphenol]
115-40-2
*
*
2
4,7-Methano-lH-indenol, 3a,4,5,6,7,7a-
hexahydro-, acetate
54830-99-8
3
3
1
4,7-Methano-lH-indenol, 3a,4,5,6,7,7a-
hexahydro-, propanoate
68912-13-0
1
3
1
4-Chloro-2-methylbenzylamine
95-69-2
3
2
2
4-Chlorobenzylamine
106-47-8
3
1
1
4-Ethenylcyclohexene
100-40-3
2
2
1
4-Hydroxybenzoic acid
99-96-7
2
2
1
4-Hydroxybenzoic acid, ethyl ester
120-47-8
1
3
1
4-Octylphenol
1806-26-4
3
3
1
9,10-Anthracenedione, l,4-bis[(4-
methylphenyl)amino]-, sulfonated,
potassium salts
125351-99-7
*
*
*
9H-Fluorene
86-73-7
3
2
2
9-Methoxy-7H-furo[3,2-g][l]benzopyran-7-
one
298-81-7
3
*
1
9-Octadecenoic acid (9Z)-, barium salt (2:1)
591-65-1
*
2
2
-------
Acting Administrator Nishida
Page 53
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
Amides, coco, N,N-bis(hydroxyethyl)
68603-42-9
3
3
1
Anthracene
120-12-7
2
2
2
Benz[a]anthracene
56-55-3
3
2
3
Benzenamine, 4,4'-[(l-
methylethylidene)bis(4,l-phenyleneoxy)]bis-
13080-86-9
3
1
3
Benzeneethanamine, .alpha.-methyl-
300-62-9
2
2
1
Benzeneethanol
60-12-8
3
2
1
Benzenepentanol,.gamma.-methyl-
55066-48-3
1
3
1
Benzenepropanal, 4-(l,l-dimethylethyl)-
alpha-methyl-
80-54-6
2
3
1
Benzenepropanoic acid, 3,5-bis(l,l-
dimethylethyl)-4-hydroxy-, l,l'-[(l,2-dioxo-
l,2-ethanediyl)bis(imino-2,l-
ethanediyl)]ester
70331-94-1
3
2
2
Benzenepropanoic acid, 3,5-bis(l,l-
dimethylethyl)-4-hydroxy-, l,l'-[2,2-bis[[3-
[3,5-bis(l,l-dimethylethyl)-4-
hydroxyphenyl]- l-oxopropoxy]methyl]-l,3-
propanediyl] ester
6683-19-8
1
3
2
Benzenepropanoic acid, 3,5-bis(l,l-
dimethylethyl)-4-hydroxy-, octadecyl ester
2082-79-3
2
3
1
Benzenesulfonamide, N-(4-amino-9,10-
dihydro-3-methoxy-9,10-dioxo-l-
anthracenyl)-4-methyl-
81-68-5
3
2
2
Benzenesulfonic acid, [[4-[[4-
(phenylamino)phenyl][4-(phenylimino)-2,5-
cyclohexadien-1-
ylidene] methyl] phenyl] amino]-
1324-76-1
*
3
3
Benzenesulfonic acid, 2-amino-5 methyl-
88-44-8
2
3
2
Benzenesulfonic acid, 5-chloro-2-[2-(2-
hydroxy-l-naphthalenyl)diazenyl]-4-methyl-
,barium salt (2:1)
5160-02-1
1
3
2
Benzenesulfonic acid, C10-16-alkyl derivs.
68584-22-5
1
3
1
Benzenesulfonic acid, mono-C10-16-alkyl
derivs., sodium salts
68081-81-2
*
3
1
Benzo[a]pyrene
50-32-8
3
2
3
-------
Acting Administrator Nishida
Page 54
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
Benzoic acid, 2-[(3,5-dibromo-4-
hydroxyphenyl)(3,5-dibromo-4-oxo-2,5-
cyclohexadien-l-ylidene)methyl]-, ethyl
ester
1176-74-5
3
*
2
Benzoic acid, 2-[2-[l-[[(2,3-dihydro-2-oxo-
1H- benzimidazol-5-yl)amino]carbonyl]-2-
oxopropyl]diazenyl]-
31837-42-0
1
3
2
Benzoic acid, 4-hydroxy-, butyl ester
94-26-8
1
3
1
Benzoic acid, 4-hydroxy-, propyl ester
94-13-3
2
3
1
Benzoyl chloride
98-88-4
3
2
1
Bis(2,4-dihydroxyphenyl)methanone
131-55-5
3
*
1
Boric acid (H3B03)
10043-35-3
2
3
1
Bromodichloromethane
75-27-4
3
1
2
Bromoethene
593-60-2
3
1
2
Bromomethane
74-83-9
2
2
1
Butanedioic acid, 2-sulfo-, l,4-bis(2-
ethylhexyl) ester, sodium salt (1:1)
577-11-7
2
3
1
C.I. Pigment Green 7
1328-53-6
*
3
2
C.I. Sulphur Orange 1
1326-49-4
3
*
2
Carbamic acid, ethyl ester
51-79-6
3
1
1
Carbon disulfide
75-15-0
2
3
1
Chloramide
10599-90-3
3
3
1
Chlorine oxide (CI02)
10049-04-4
3
2
1
Chlorobenzene
108-90-7
2
3
1
Chloromethane
74-87-3
2
2
1
Chloromethoxymethane
107-30-2
3
1
1
Cyclohexanol, 2-(l,l-dimethylethyl)-, 1-
acetate
88-41-5
2
3
1
Cyclohexanol, 4-(l,l-dimethylethyl)-, 1-
acetate
32210-23-4
2
3
1
Decanedioic acid, l,10-bis(l,2,2,6,6-
pentamethyl-4-piperidinyl) ester
41556-26-7
3
3
2
Decanoic acid,
2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-
nonadecafluoro-
335-76-2
1
2
3
-------
Acting Administrator Nishida
Page 55
January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
D-Glucitol, l,3:2,4-bis-0-[(3,4-
dimethylphenyl)methylene]-
135861-56-2
*
2
2
Dibenz[a,h] anthracene
53-70-3
3
2
2
Dibromochloromethane
124-48-1
3
2
2
Dibromomethane
74-95-3
2
1
1
Dihydro-3-(octen-l-yl)-2,5-furandione
26680-54-6
*
3
1
Dimethylbenzene
1330-20-7
1
3
1
Dinitrotoluene (technical grade)
99749-33-4
*
*
*
Dodecanoic acid
143-07-7
2
3
1
Ethanaminium, N,N,N-triethyl-,
1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-
heptadecafluoro-l-octanesulfonate (1:1)
56773-42-3
3
*
3
Ethanol, 2,2'-(methylimino)bis-
105-59-9
1
3
1
Ethanol, 2,2'-iminobis-, N-coco alkyl derivs.
61791-31-9
3
3
1
Fluoroethene
75-02-5
3
1
2
Hexabromo-l,l'-biphenyl
36355-01-8
3
2
3
Hexachlorocyclohexane
608-73-1
3
2
3
Hexanedioic acid, 1,6-diisononyl ester
33703-08-1
1
3
1
Indium phosphide (InP)
22398-80-7
3
*
2
Isocyanatomethane
624-83-9
1
1
1
Mercury and Mercury Compounds
7439-97-6
3
3
3
Methanamine, N-methyl-N-nitroso-
62-75-9
3
3
2
Methanesulfonic acid, methyl ester
66-27-3
3
*
1
Methanol
67-56-1
2
3
1
Methylbenzene
108-88-3
2
3
1
Methylium, [4-(dimethylamino)phenyl]bis[4-
(ethylamino)-3-methylphenyl]-, acetate (1:1)
72102-55-7
3
2
2
N-(2-methylphenyl)-3-oxobutanamide
93-68-5
2
2
1
N-(4-Chlorophenyl)-2-hydroxy-9H-carbazole-
3-carboxamide
132-61-6
3
*
2
N-(4-ethoxyphenyl)acetamide
62-44-2
3
2
1
N,N,N',N',N",N"-Hexamethylphosphoric
triamide
680-31-9
2
1
1
N,N-Dimethylacetamide
127-19-5
1
2
1
N,N-Dimethylcarbamyl chloride
79-44-7
3
1
1
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Acting Administrator Nishida
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January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
N-[2-[2-(2-Bromo-4,6-
dinitrophenyl)diazenyl]- 5-
(diethylamino)phenyl]acetamide
52697-38-8
3
2
2
N-[4-(Acetylamino)phenyl]-4-[2-[5-
(aminocarbonyl)-2-chlorophenyl]diazenyl]-3-
hydroxy-2-naphthalenecarboxamide
12236-64-5
3
*
2
N-[5-[Bis[2-(acetyloxy)ethyl]amino]-2-[2-(2-
bromo-4,6-dinitrophenyl)diazenyl]-4-
ethoxyphenyl]acetamide
12239-34-8
3
2
2
Neodecanoic acid, barium salt (2:1)
55172-98-0
*
2
3
N-ethyl-N-nitroso-ethanamine
55-18-5
3
2
2
Nitrobenzene
98-95-3
2
2
1
N-Methyl-N-[(9Z)-l-oxo-9-octadecen-l-
yl]glycine
110-25-8
3
*
2
N-methyl-N'-nitro-N-nitrosoguanidine
70-25-7
3
*
1
N-Methyl-N-nitrosourea
684-93-5
3
1
1
N-nitroguanidine
556-88-7
1
*
1
Octadecanoic acid
57-11-4
1
3
2
Octadecanoic acid, l,l'-[2,2-bis[[(l-
oxooctadecyl)oxy]methyl]-l,3-propanediyl
ester
115-83-3
*
3
1
Octadecanoic acid, calcium salt (2:1)
1592-23-0
*
3
1
Octadecanoic acid, magnesium salt (2:1)
557-04-0
1
3
1
Octadecanoic acid, methyl ester
112-61-8
*
2
1
Octadecanoic acid, tridecyl ester
31556-45-3
*
3
1
Octanoic acid
124-07-2
1
3
1
O-Dinitrobenzene
528-29-0
1
1
2
Oxirane
75-21-8
3
2
1
Oxirane, 2,2',2",2'"-[l,2-
ethanediylidenetetrakis(4,l-
phenyleneoxymethylene)]tetrakis-
7328-97-4
3
3
3
Perchloric acid
7601-90-3
3
1
1
Peroxide, l,l'-(l,l,4,4-tetramethyl-l,4-
butanediyl)bis[2-(l,l-dimethylethyl)
78-63-7
3
2
3
Peroxide, l,l'-(l,l,4,4-tetramethyl-2-
butyne- l,4-diyl)bis[2-(l,l dimethylethyl)
1068-27-5
3
1
3
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Acting Administrator Nishida
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January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
Peroxide, l,l'-(3,3,5-
trimethylcyclohexylidene)bis[2-(l,l-
dimethylethyl)
6731-36-8
3
2
3
Peroxide, l,l'-[l,3(or 1,4) phenylenebis(l-
methylethylidene)]bis[2-(l,l-dimethylethyl)
25155-25-3
3
2
3
Phenanthrene
85-01-8
2
2
2
Phenol
108-95-2
2
3
1
Phenol, 2,4-bis(l,l-dimethylethyl)-, 1,1',1"-
phosphite
31570-04-4
1
3
2
Phosphonic acid, P-[[3,5-bis(l,l-
dimethylethyl)-4-hydroxyphenyl] methyl]-,
monoethyl ester, calcium salt (2:1)
65140-91-2
*
2
2
Phosphoric acid, 2-ethylhexyl ester,
potassium salt
68550-93-6
*
*
1
Phosphoric acid, diethyl ester
598-02-7
1
2
1
Phosphoric acid, dimethyl ester
813-78-5
*
1
1
Phosphorodithioic acid, 0,0-diethyl ester
298-06-6
3
1
1
Phosphorodithioic acid, 0,0-dimethyl ester
756-80-9
3
2
1
Polychlorinated Naphthalenes (PCNs)
NOCAS
1
3
3
Propanenitrile, 3-[[2-(acetyloxy)ethyl][4-
[(6,7-d ichloro-2-
benzothiazolyl)azo]phenyl]amino ]-
127126-02-7
3
*
*
Propanenitrile, 3-[[2-(acetyloxy)ethyl][4-[2-
(2,6-dichloro-4-
nitrophenyl)diazenyl]phenyl]amino]
5261-31-4
3
2
2
Propanenitrile, 3-[[4-[2-(2,6-dibromo-4-
nitrophenyl)diazenyl]phenyl]ethylamino]
55281-26-0
*
2
2
Propanoic acid, 3,3'-thiobis-, 1,1'-
didodecylester
123-28-4
3
2
1
Propanoic acid, 3,3'-thiobis-, 1,1'-
dioctadecylester
693-36-7
2
2
1
Pyrene
129-00-0
2
1
2
Quartz (Si02)
14808-60-7
3
3
2
Quino[2,3-b]acridine-7,14-dione, 5,12-
dihydro-
1047-16-1
1
3
2
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Acting Administrator Nishida
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January 26, 2021
Chemical Name
CASRN
2012
Hazard
Score
2012
Exposure
Score
2012
Persistence/
Bioaccumulation
Score
Quino[2,3-b]acridine-7,14-dione, 5,12-
dihydro-2,9-dimethyl-
980-26-7
2
3
2
Quinoline
91-22-5
3
2
1
Retinoic acid
302-79-4
3
*
2
Sulfuric acid monododecyl ester sodium salt
(1:1)
151-21-3
2
2
1
Sulfuric acid, diethyl ester
64-67-5
3
2
1
Sulfuric acid, dimethyl ester
77-78-1
3
1
1
Sulfuric acid, mono-C10-16-alkyl esters,
ammonium salts
68081-96-9
3
3
1
Tributylstannane
688-73-3
3
*
3
Trichloromethyl benzene
98-07-7
3
1
1
Urea, N-ethyl-N-nitroso-
759-73-9
3
1
1
Zinc oxide (ZnO)
1314-13-2
1
2
3
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January 26, 2021
Attachment G: Authoritative sources used to generate candidate chemicals for the TSCA Workplan
method
Source: US EPA, TSCA Workplan Chemicals: Methods Document. Pg. 3-4 (2012)
Prioritization Factor
Sources
Carcinogens
• IRIS: 1986 Class A, Bl; 1996 Known or Probable; 1999 or 2005
Carcinogenic
• IARC Carcinogens, Group 1, 2A
• NTP Known Carcinogens
Persistent, Bioaccumulative,
• TRI PBT Rule
Toxic (PBT)
• Great Lakes Binational PBT
• Canadian P, B, and T (all three criteria met)
• LRTAP POPS
• Stockholm POPs
Children's Health
• IRIS: Repro/Dev (RfD or RfC for repro or dev)
• NTP CERHR: Infants any effect or pregnant women any effect
• Cal Prop 65 Reproductive
Children's Product Use
• Reported in products intended for use by children in 2020 CDR*
• Washington State Children's List
Neurotoxicity
• IRIS
Biomonitoring
• NHANES
• Drinking water contaminant monitoring
• Fish tissue studies
*For the 2012 TSCA Workplan, EPA used the 2006 Inventory Update Reporting (IUR); more current use data are
available to EPA in the most recent Chemical Data Reporting (CDR).
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Attachment H: Excerpts from EPA risk assessment guidelines
We note here the principles outlined in EPA's risk assessment guidelines for determining a potential hazard:
• EPA's Guidelines for Developmental Toxicity Risk Assessment note that "The minimum evidence
necessary to judge that a potential hazard exists generally would be data demonstrating an adverse
developmental effect in a single, appropriate, well-conducted study in a single experimental animal
species."
• EPA's Guidelines for Reproductive Toxicity Risk Assessment: "The minimum evidence necessary to
determine if a potential hazard exists would be data demonstrating an adverse reproductive effect in
a single appropriate, well-executed study in a single test species."
We note here the principles outlined in EPA's risk assessment guidelines to judge the lack of a hazard:
• EPA's Guidelines for Developmental Toxicity Risk Assessment: "The minimum evidence needed to
judge that a potential hazard does not exist would include data from appropriate, well-conducted
laboratory animal studies in several species (at least two) which evaluated a variety of the potential
manifestations of developmental toxicity and showed no developmental effects at doses that were
minimally toxic to the adult."
• EPA's Guidelines for Reproductive Toxicity Risk Assessment: "The minimum evidence needed to
determine that a potential hazard does not exist would include data on an adequate array of
endpoints from more than one study with two species that showed no adverse reproductive effects
at doses that were minimally toxic in terms of inducing an adverse effect."
• EPA Guidelines for Carcinogen Risk Assessment: A determination of "Not Likely to Be Carcinogenic to
Humans" requires robust evidence as follows:
"This descriptor is appropriate when the available data are considered robust for deciding that there
is no basis for human hazard concern. In some instances, there can be positive results in
experimental animals when there is strong, consistent evidence that each mode of action in
experimental animals does not operate in humans. In other cases, there can be convincing evidence
in both humans and animals that the agent is not carcinogenic. The judgment may be based on data
such as:
o animal evidence that demonstrates lack of carcinogenic effect in both sexes in well-
designed and well-conducted studies in at least two appropriate animal species (in the
absence of other animal or human data suggesting a potential for cancer effects),
o convincing and extensive experimental evidence showing that the only carcinogenic
effects observed in animals are not relevant to humans,
o convincing evidence that carcinogenic effects are not likely by a particular exposure
route (see Section 2.3), or
o convincing evidence that carcinogenic effects are not likely below a defined dose range.
A descriptor of "not likely" applies only to the circumstances supported by the data. For
example, an agent may be "Not Likely to Be Carcinogenic" by one route but not necessarily by
another. In those cases that have positive animal experiment(s) but the results are judged to be not
relevant to humans, the narrative discusses why the results are not relevant.
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