[Federal Register Volume 90, Number 230 (Wednesday, December 3, 2025)]
[Notices]
[Pages 55726-55735]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-21776]
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ENVIRONMENTAL PROTECTION AGENCY
[EPA-HQ-OPPT-2018-0438; FRL-11608-05-OCSPP]
Formaldehyde; Updated Draft Risk Calculation Memorandum; Notice
of Availability and Request for Comment
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: The Environmental Protection Agency (EPA or ``the Agency'') is
announcing the availability of and soliciting public comment on an
Updated Draft Risk Calculation Memorandum (or ``Draft Memorandum'') to
inform a Revised Draft Risk Evaluation for Formaldehyde Under the Toxic
Substances Control Act (TSCA). The purpose of risk evaluations under
TSCA is to determine whether a
[[Page 55727]]
chemical substance presents an unreasonable risk of injury to human
health or the environment, without consideration of costs or non-risk
factors, including unreasonable risk to potentially exposed or
susceptible subpopulations identified as relevant to the risk
evaluation by EPA, under the conditions of use (COUs). Consistent with
statutory obligations and Executive Order 14303, Restoring Gold
Standard Science, EPA remains committed to the highest standards of
scientific integrity and reliance on the best available scientific
information. To that end, and after further consideration of comments
raised during the scientific peer review process, EPA is reconsidering
the use of certain hazard values in the formaldehyde risk evaluation.
This Notice, Draft Memorandum, and the materials included in the docket
provide the science and science policy basis for determining how the
revised draft inhalation point of departure (POD) impacts the
corresponding draft margin of exposure (MOE) estimates and the risk
determination for formaldehyde under TSCA. Although the Agency is also
providing a revised draft occupational exposure value, EPA is not
changing its position that formaldehyde poses unreasonable risk of
injury to human health. As such, the Agency is continuing work on a
proposed risk management rule for formaldehyde as required by TSCA to
ensure statutory deadlines are met and necessary protections are not
delayed. EPA is also seeking additional information, specific to how
formaldehyde is manufactured and used, which may inform the risk
management of formaldehyde. After public comment, the Agency will
determine if the proposed revisions discussed in this action warrant
updating the Risk Evaluation for Formaldehyde under TSCA.
DATES: Comments must be received on or before February 2, 2026.
ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPPT-2018-0438, online at https://www.regulations.gov. Follow the online instructions for submitting
comments. Do not submit electronically any information you consider to
be Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Additional instructions on
commenting and visiting the docket, along with more information about
dockets generally, is available at https://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
For technical information: Jeffery Putt, Existing Chemicals Risk
Management Division (7404M), Office of Pollution Prevention and Toxics
(OPPT), Office of Chemical Safety and Pollution Prevention (OCSPP),
Environmental Protection Agency, 1200 Pennsylvania Ave. NW, Washington,
DC 20460-0001; telephone number: (202) 564-3703; email address:
[email protected].
For general information: The TSCA Assistance Information Service
Hotline, Goodwill Vision Enterprises, 422 South Clinton Ave.,
Rochester, NY 14620; telephone number: (800) 471-7125 or (202) 554-
1404; email address: [email protected].
SUPPLEMENTARY INFORMATION:
I. Executive Summary
A. Does this action apply to me?
This action is directed to the public in general and may be of
particular interest to those involved in the manufacture (defined under
TSCA section 3(9) to include import), processing, distribution, use,
and disposal of formaldehyde, related industry trade organizations,
non-governmental organizations with an interest in human and
environmental health, state and local governments, Tribal Nations, and/
or those interested in the assessment of risks involving chemical
substances and mixtures regulated under TSCA. As such, the Agency has
not attempted to describe all of the specific entities to which this
action might apply. If you need help determining applicability of this
action, consult the technical contact listed under FOR FURTHER
INFORMATION CONTACT.
B. What is the Agency's authority for taking this action?
The Agency prepared this Draft Memorandum under the Toxic
Substances Control Act (TSCA) (section 6, 15 U.S.C. 2605), which
requires that EPA conduct risk evaluations on chemical substances and
identifies the minimum components the Agency must include in all
existing chemical substance risk evaluations. Each risk evaluation must
be conducted consistent with the best available science, be based on
the weight of scientific evidence, and consider reasonably available
information, pursuant to 15 U.S.C. 2625(h), (i), and (k). See also the
implementing procedural regulations at 40 CFR part 702. Consistent with
statutory obligations and Executive Order (E.O.) 14303 (Ref. 1),
Restoring Gold Standard Science, EPA is committed to the highest
standards of scientific integrity and reliance on the best available
scientific information.
C. What action is the Agency taking?
EPA is announcing the availability of and soliciting public comment
on the Draft Memorandum and supporting materials in the docket. The
purpose of the Draft Memorandum, including this Notice and additional
draft documents in the docket, is to provide the rationale for why the
Agency is considering a revised acute inhalation POD, revised
uncertainty factors, and corresponding revised MOE calculations. EPA
continues to conclude that exposure to formaldehyde at sufficiently
high exposures for sustained duration can lead to cancer in humans.
Additionally, EPA followed the recommendations of federal advisory
committees and has concluded that managing acute sensory irritation
will be health-protective against other effects, including cancer.
Therefore, given the use of a threshold approach, it is not necessary
for the Agency to provide a separate quantitative cancer assessment.
EPA is seeking comments on all aspects of the Draft Memorandum,
including this approach.
D. What should I consider as I prepare my comments?
1. Submitting CBI. Do not submit Confidential Business Information
to EPA through https://www.regulations.gov or email. If you wish to
include CBI in your comment, please follow the applicable instructions
at https://www.epa.gov/dockets/commenting-epa-dockets#rules and clearly
mark the information that you claim to be CBI. Information so marked
will not be disclosed except in accordance with procedures set forth in
40 CFR parts 2 and 703, as applicable.
2. Tips for preparing your comments. When preparing and submitting
your comments, see the commenting tips at https://www.epa.gov/dockets/commenting-epa-dockets.
II. Background
A. What is formaldehyde?
Formaldehyde is a colorless, flammable gas at room temperature and
has a strong odor. Formaldehyde is found nearly everywhere. People and
animals produce and release formaldehyde. Formaldehyde is also produced
when organic material including leaves, plants, and woodchips decay.
Formaldehyde is also produced and released into the air when things
burn, such as when cars emit exhaust, when furnaces and stoves operate,
through forest fires, burning candles,
[[Page 55728]]
and smoking. Finally, formaldehyde is used to make many products and
articles such as composite wood products and other building materials,
plastics, pesticides, paints, adhesives, and sealants. Industry uses
formaldehyde due to its ability to combine and react with many other
chemical substances and to make resilient structures that are widely
used in manufacturing. Information from the 2016 Chemical Data
Reporting for formaldehyde indicates that its production volume is
between 1 billion and 5 billion pounds per year (manufacture and
import) (Ref. 2).
Short-term inhalation exposure to high levels of formaldehyde can
cause sensory irritation and respiratory effects. Short-term skin
contact can cause sensitization. Exposure over longer periods can also
cause respiratory effects and cancer. The complex toxicology and
exposure profiles for formaldehyde make its evaluation challenging. The
formaldehyde sources that EPA evaluated in the TSCA risk evaluation,
and this Draft Memorandum, involve, in general, the production and use
of products that are subject to TSCA (as opposed to products that are
specifically excluded from TSCA under 15 U.S.C. 2602(2)(B), such as
pesticides).
B. Regulatory History for the Formaldehyde Risk Evaluation
In December 2019, EPA designated formaldehyde as a high-priority
substance for risk evaluation under TSCA (84 FR 71924) [FRL-10003-15]
(Ref. 3). EPA's OCSPP evaluates risks from formaldehyde under both TSCA
and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). A
draft scope of the formaldehyde risk evaluation under TSCA was publicly
released in April 2020 (85 FR 22733) [FRL-10008-05] (Ref. 4), and after
receiving public comment, EPA issued the final scope of the
formaldehyde risk evaluation in September 2020 (85 FR 55281) [FRL-
10013-90] (Ref. 5). In March 2024, EPA released a draft risk evaluation
(89 FR 18933) [FRL-11608-03-OCSPP] (Ref. 6) for public comment and
external scientific peer review. In January 2025, EPA published a final
risk evaluation for formaldehyde (90 FR 316) [FRL-11608-04] (Ref. 7).
From January 2021 through January 2025, OCSPP leadership directed that
OPPT and the Office of Pesticide Programs (OPP) rely upon and use the
chronic non-cancer reference concentration (RfC) and cancer inhalation
unit risk (IUR) that were being developed and were subsequently
finalized by the Integrated Risk Information System (IRIS) program.
Consistent with statutory obligations and E.O. 14303, Restoring Gold
Standard Science, EPA is committed to the highest standards of
scientific integrity and reliance on the best available scientific
information. As such, OCSPP has re-evaluated the use of the IRIS
chronic RfC and cancer IUR.
EPA leveraged work products and resources across the Agency in its
development of the Risk Evaluation for Formaldehyde, including
consideration of hazard information from EPA's IRIS Toxicological
Review of Formaldehyde (Inhalation). A draft version of the IRIS
toxicological review was published in April 2022 (Ref. 8) and finalized
in August 2024 (Ref. 9). The draft IRIS document was also the subject
of external peer review by the National Academies of Sciences,
Engineering, and Medicine (NASEM) (Ref. 10).
In addition, EPA leveraged multiple federal advisory committees and
their reports to support the external peer review of formaldehyde
during the risk evaluation process, including NASEM (Ref. 10), the
Human Studies Review Board (HSRB) (Ref. 11), and the Science Advisory
Committee on Chemicals (SACC) (Ref. 12).
The formaldehyde risk evaluation includes a series of related
assessments called technical support documents (TSDs). Each document
contained sub-assessments that inform adjacent, ``downstream'' TSDs.
These TSDs addressed comments from both public and peer review. The
components of the Risk Evaluation for Formaldehyde, including (but not
limited to) each TSD and responses to peer review and public comments,
continue to be available in the docket for this Notice.
The Draft Memorandum is supported by information in the docket
which includes this Notice, supporting materials such as risk
calculators for workers, consumers, and the general population--all of
which are available in the docket. The docket also includes redline
versions of the Revised Draft Human Health Hazard Assessment, Revised
Draft Human Health Risk Assessment, Revised Draft Executive Summary,
and Revised Draft Unreasonable Risk Determination to show the impact of
the revisions on the overall evaluation and its components, if the
Draft Memorandum were finalized.
C. Science Policy Context
As EPA developed and finalized documents for the FIFRA formaldehyde
risk assessment and TSCA risk evaluation from January 2021 through
December 2024, as described above, the Agency used, where relevant, the
chronic non-cancer RfC and cancer IUR value that were being developed
and were subsequently established by EPA's IRIS program. The IRIS draft
toxicological review for formaldehyde was released as draft in April
2022 (Ref. 8), reviewed by NASEM (NASEM, 2023) (Ref. 10), and
subsequently finalized in August of 2024 (U.S. EPA, 2024a) (Ref. 9).
Consistent with EPA's Rule for the Protection of Human Subjects,
the Agency solicited peer review on four acute inhalation human studies
(Mueller et al., 2013 (Ref. 13); Lang et al., 2008 (Ref. 14); Kulle et
al., 1987 (Ref. 15); Andersen and M[oslash]lhave, 1983 (Ref. 16)) along
with the acute inhalation proposed PODs for formaldehyde and associated
rationale from HSRB in October 2022 (Ref. 11), May 2023 (Ref. 17), and
July 2023 (Ref. 18). HSRB agreed with EPA's assessment that the four
human studies met appropriate scientific and ethical standards and were
appropriate for the Agency to rely upon to support decision making. The
HSRB also made multiple recommendations to EPA to improve the
scientific analysis. Consistent with the findings of the NASEM (2023)
(Ref. 10), HSRB was critical of observational studies, such as Hanrahan
et al. (1984) (Ref. 19), which were used in the draft EPA IRIS
toxicological review for the RfC and did not support using these
studies to derive a quantitative POD. Instead, HSRB supported the use
of the acute sensory irritation studies performed in the clinical
setting for deriving or providing qualitative support for PODs.
Included among the recommendations from the HSRB was a recommendation
that ``EPA conduct a more coordinated approach [to peer review] with
other entities (e.g., NASEM, TSCA Science Advisory Committee on
Chemicals (SACC)) . . .'' (p. 9 of HSRB July 2023 (Ref. 18)).
In March 2024, EPA released the Draft Risk Evaluation for
Formaldehyde and the Draft Human Health Hazard Assessment for
Formaldehyde (U.S. EPA, 2024c) (Ref. 20). The draft TSCA risk
evaluation relied upon the chronic RfC and IUR values from the draft
IRIS toxicological review because the draft IRIS assessment had not yet
been finalized. EPA specifically solicited input from the SACC on the
utility of the EPA IRIS RfC and IUR for use in the TSCA risk
evaluation. In response to the HSRB and in accordance with the
Procedures for Chemical Risk Evaluation Under the Toxic Substances
Control Act (TSCA) (40 CFR part 702) requirement to conduct peer review
on risk evaluations, OCSPP convened the SACC in May 2024 to evaluate
aspects
[[Page 55729]]
of the hazard and exposure assessments for formaldehyde (Ref. 21). The
SACC minutes and final report were released on August 2, 2024 (U.S.
EPA, 2024b) (Ref. 12). As described in detail in the following
sections, the SACC was critical of the IRIS RfC and IUR and largely
advised against using these hazard values in the formaldehyde risk
evaluation. Consistent with the direction from EPA leadership at the
time, the 2024 TSCA risk evaluation continued to rely on these EPA IRIS
values to assess risk from certain exposure scenarios (Ref. 7).
Given the critical scientific concerns on the scientific
interpretations of MOA, dose response, and health outcome information
in the EPA IRIS assessment (as raised by two federal advisory
committees, HSRB and SACC), and to be consistent with E.O. 14303, OCSPP
has revisited the use of the IRIS chronic RfC and cancer IUR values for
purposes of the Agency's TSCA risk evaluation of formaldehyde. In
addition, OCSPP developed the revised draft POD and uncertainty/
extrapolation factor derived from the acute inhalation controlled human
exposure studies. The following section describes the scientific
rationale and weight of scientific evidence for the hazard
identification in the Draft Memorandum.
1. Peer Review Findings and Recommendations
In the Preface to the 2023 NASEM report titled, Review of EPA's
2022 Draft [IRIS] Formaldehyde Assessment (Ref. 10), the Chair stated
that ``. . . the committee did not conduct an independent hazard
assessment or recommend alternative toxicity values.'' In other words,
the NASEM panel did not perform a thorough review of the individual
studies or critically evaluate alternative approaches to the
formaldehyde hazard characterization. In contrast, the charge questions
to both the HSRB and the SACC did require a critical evaluation of the
formaldehyde studies. The NASEM panel did, however, conduct a case
study evaluating the Hanrahan (1984) study (Ref. 19) and was highly
critical of the IRIS evaluation and use of the study. Specifically, the
NASEM panel noted that ``The committee could not replicate the agency's
process with complete fidelity, and we identified inconsistencies in
EPA's evaluation'' (p. 139 of U.S. EPA, 2024b) (Ref. 12).
Both the HSRB and SACC provided detailed, independent critiques of
toxicology and epidemiology studies, hazards identified, uncertainty/
extrapolation factors, and provided recommendations for alternative POD
and hazard identification approach(es). HSRB and SACC peer reviewers
called into question whether the EPA IRIS assessment complied with the
TSCA requirement to use ``best available science'' and ``weight of
scientific evidence'' with respect to interpretation to various
studies, integration of evidence, and MOA analysis. For example, the
SACC report (p. 84 of U.S. EPA, 2024b) (Ref. 12) states that ``Many
Committee members considered that the cancer Inhalation Unit Risk
(IUR). . . does not integrate all available data, despite the
overwhelming weight of scientific evidence (WOSE) that the non-
genotoxic mode of action (MOA) predominates and would be protective of
any other MOA for formaldehyde carcinogenicity.'' In addition, the SACC
noted that the EPA IRIS assessment contains ``an incorrect application
of mode of action analysis and an incorrect interpretation of all
available data'' (p. 63).
With respect to the cancer IUR, the SACC stated that the IUR was
``not supported by a proper holistic interpretation of the collected
data and should not be used by OPPT for risk assessment.'' The SACC
report also states that ``the majority of the information presented in
session did not favor a IUR approach and rather supported a threshold
approach'' (p. 22).
With regards to the RfC, the SACC noted that the studies identified
by EPA IRIS are ``unreliable for identifying a point of departure'' and
``do not adequately address the chosen endpoint due to several
limitations, including but not limited to the ability to determine
causality specific to formaldehyde, confounders that were not addressed
and including use of self-completed questionnaires instead of measured
health effects which decreases the reliability of results'' (p. 34).
The SACC noted the Agency could ``consider using sensory irritation as
an end point for Points of Departure (POD) as a treatment effect that
would protect against all downstream events including a carcinogenic
response'' (p. 84). Similarly, the HSRB stated that ``EPA should
consider that PODs for sensory irritation could be used as a lower
bound for potential adverse effects'' (p. 9 of HSRB July 2023) (Ref.
18).
2. Point of Departure for the OCSPP Formaldehyde Risk Assessments
a. Use of Sensory Irritation as an Endpoint
In the draft and final TSCA risk evaluations for formaldehyde, EPA
selected sensory irritation as the basis for acute inhalation POD
derivation; use of sensory irritation as the critical effect was
supported by the HSRB and SACC. Use of sensory irritation is consistent
with other national and international exposure limits (see Appendix A
of the Human Health Hazard Assessment for Formaldehyde (Ref. 20))
derived under a range of regulatory and advisory contexts for general
population and occupational exposures.
EPA identified four controlled human exposure studies (Mueller et
al., 2013 (Ref. 13); Lang et al., 2008 (Ref. 14); Kulle et al., 1987
(Ref. 15); Andersen and M[oslash]lhave, 1983 (Ref. 16)) to inform
selection of an acute peak exposure level. The HSRB agreed with EPA's
conclusions that each of the studies were scientifically sound and
ethically conducted and could be used quantitatively and/or
qualitatively to support the acute inhalation weight of evidence (WOE)
analysis (July 2023 HSRB report) (Ref. 18).
The sensory irritation effects of formaldehyde are more responsive
to the exposure concentration than to exposure duration, which means
that formaldehyde does not adhere to Haber's Law (Shusterman et al.,
2006) (Ref. 22). Based on a review of the WOE analysis presented to the
HSRB in May 2023, the HSRB did not recommend duration adjustments for
8- or 24-hour PODs for the sensory endpoint. This was based on the lack
of support for this adjustment in the four studies presented in the WOE
and the understanding that the existing literature demonstrates that
formaldehyde does not follow Haber's Law (p. 9 of the July 2023 HSRB
report) (Ref. 18). Therefore, rather than deriving duration-adjusted
acute PODs for 8- and 24-hour average concentrations, consistent with
the approach recommended by HSRB, EPA's acute inhalation analyses in
the draft and final TSCA risk evaluation for formaldehyde focused on
identifying air concentrations that may result in sensory irritation at
any acute exposure duration.
For the Draft Memorandum and in the Revised Draft Risk Evaluation
for Formaldehyde Under the Toxic Substances Control Act (TSCA), OCSPP
is continuing to rely upon sensory irritation as the endpoint for
evaluating acute inhalation exposures in the Revised Draft.
b. Revised Draft Uncertainty/Extrapolation Factor for Intra-Human
Variability
Both the HSRB (Ref. 18) and SACC (Ref. 12) recommended that EPA
consider an intrapopulation variability uncertainty factor
(UFH) lower than the
[[Page 55730]]
default 10 times (10x) that was proposed in the draft human health
assessment for formaldehyde. Specifically, HSRB noted an uncertainty
factor is not necessary when the POD is based on sensory irritation
whereas the SACC recommended EPA consider either 1x or 3x.
Sensory irritation is a point-of-contact effect and toxicokinetic
differences across people are unlikely to contribute to human
variability in the sensory irritation response. As described in Section
2.5 of the National Resource Council (NRC; now NASEM) Standing
Operating Procedures for Developing Acute Exposure Guideline Levels for
Hazardous Chemicals (NRC, 2001) (Ref. 23), direct irritation and/or
corrosivity occurs at the point of contact such that absorption,
distribution, metabolism, excretion (ADME) characteristics are not
factors that would significantly influence the irritant toxicokinetic
response. Therefore, EPA concluded that it was appropriate to lower the
toxicokinetic component of the UFH from 3x to 1x in the
December 2024 Human Health Hazard Assessment for Formaldehyde (Ref.
20). OCSPP is continuing to use a 1x for the toxicokinetic component of
the UFH in the Draft Memorandum.
With respect to the toxicodynamic portion of the UFH, in
the December 2024 human health hazard assessment of the Risk Evaluation
for Formaldehyde, the UFH of 3x was applied to account for
human variability in toxicodynamics that may not be captured in the
controlled human exposure studies used as the basis for dose-response.
However, this conclusion does not align with the recommendation of HSRB
that specifically notes in the July 2023 report that ``younger
individuals are more sensitive to sensory irritation than older
individuals, and therefore younger individuals are an appropriate
population for intentional exposure studies when sensory irritation is
the primary objective'' (p. 9). The World Health Organization (WHO)
supports this conclusion with the following: ``There is no evidence
indicating an increased sensitivity to sensory irritation to
formaldehyde among people often regarded as susceptible (asthmatics,
children and older people). Although some studies suggest that
formaldehyde plays a role in airway sensitization, an association
between formaldehyde and lung effects or sensitization in children has
not been convincing owing to confounding factors in the studies,
including exposure to traffic-related co-pollutants.'' (p. 139 of (Ref.
24)).
Similarly, the European Chemicals Agency ECHA (2019) (Ref. 25)
states that ``In general, associations between formaldehyde and lung
effects or sensitisation in children in homes and schools have not been
convincing owing to confounding factors and chance effects. Well known
confounders for asthma are e.g., dust mites, cockroach allergen, pets
or mould.'' The German Umweltbundesamt (UBA) (2016) (Ref. 26) also
reviewed the results from epidemiological studies investigating if
there is an association between formaldehyde exposure and the induction
or exacerbation of asthma in children. UBA concluded that there is no
clear association between formaldehyde exposure in the indoor
environment and asthma in children.
At this time, for the Draft Memorandum to align with the
recommendations from the peer review panels, OCSPP is also reducing the
toxicodynamic portion of the UFH, to 1x leading to a total
UFH of 1x to evaluate inhalation exposures.
c. Revised Draft Acute Inhalation POD
In the EPA's December 2024 human health hazard assessment of the
final TSCA risk evaluation for formaldehyde, the acute POD was derived
based on sensory irritation effects for each of the three studies
(Mueller et al., 2013 (Ref. 13); Lang et al., 2008 (Ref. 14); Kulle et
al., 1987 (Ref. 15)) that HSRB supported using quantitatively
(summarized in Table 1). An acute POD of 0.5 ppm (parts per million)
was selected in 2024 based on the 95 percent lower confidence limit of
the benchmark concentration (BMCL10) and no-observed-adverse-effect
concentration (NOAEC) identified for a 3-hour exposure in Kulle et al.
(1987) (Ref. 15). The acute inhalation POD of 0.5 ppm is provided later
in this Notice.
The SACC recommended EPA ``Carefully reevaluate the available data
to determine if 0.5 ppm or a concentration that is lower or higher''
should be used as a POD (p. 28). The SACC further recommended EPA
``Follow the HSRB recommendation to rely on Mueller et al. (2013) (Ref.
13) and Lang et al. (2008) (Ref. 14) to derive a POD consistent with
the best available science using a weight of the evidence approach''
(p. 35). This recommendation appears to be based on the statement on p.
10 of the HSRB July 2023 report (Ref. 18), which states ``Of the
studies the HSRB evaluated, the controlled chamber studies (e.g.,
Mueller et al. (2013) (Ref. 13) and Lang et al. (2008) (Ref. 14)) have
preferred study design and greater scientific rigor than the
observational studies (e.g., Hanrahan et al. (1984) (Ref. 19) and Liu
et al. (1991) (Ref. 27))''. Therefore, it does not preclude the other
two controlled chamber studies (Kulle et al. 1987 (Ref. 15); Anderson
and M[oslash]lhave 1983 (Ref. 16)) from similarly being considered as
best available science for the WOE evaluation. The HSRB determined that
Kulle et al. (1987) (Ref. 15) and Lang et al. (2008) (Ref. 14) provided
reliable data for use in a WOE analysis to determine a POD for acute
inhalation exposure to formaldehyde and that Mueller et al. (2013)
(Ref. 13) provided reliable semi-quantitative data (p. 5 and p. 6 of
July 2023 HSRB report) (Ref. 18).
All the studies tested constant exposure concentrations to
formaldehyde and did not observe any effects at 0.5 ppm or below. In
addition to constant exposure treatment groups, Lang et al. (2008)
(Ref. 14) and Mueller et al. (2013) (Ref. 13) also included treatment
groups with 15-minute peaks to higher concentrations. A NOAEC for these
variable exposures was established at 0.3 ppm with 0.6 ppm peaks in
Lang et al. (2008) (Ref. 14). In Mueller et al. (2013) (Ref. 13), there
was an increase in reported irritation in hypersensitive subjects at
0.3 ppm with 0.6 ppm peaks and 0.4 ppm with 0.8 ppm peaks,
respectively.
Given the findings in the controlled human exposure studies
reviewed by the HSRB, particularly Mueller et al. (2013) (Ref. 13),
coupled with the reduction of the UFH to 1x described
earlier in this Notice, using the 2024 acute inhalation POD of 0.5 ppm
may not be adequately health protective. Specifically, 0.5 ppm POD / 1x
UFH leads to a value of 0.5 ppm where effects in
hypersensitive subjects were reported at 0.3 ppm with 0.6 ppm peaks and
0.4 ppm with 0.8 ppm peaks. As noted earlier, there were no effects
observed when exposure concentrations were constant at 0.5 ppm or
below. Consequently, considering the totality of the evidence, the
acute inhalation POD for formaldehyde has been appropriately
supplemented. Based on the same four robust controlled human exposure
studies, 0.3 ppm is considered a health-protective POD for evaluating
acute inhalation exposures where there was a lack of reported findings
in the controlled human studies at this constant exposure
concentration.
For the Draft Memorandum, OCSPP is updating the draft acute
inhalation POD to 0.3 ppm for formaldehyde.
[[Page 55731]]
d. Use of the Acute Inhalation POD To Protect for All Durations,
Including Cancer
The SACC states (p.84) that ``The inhaled formaldehyde is not
distributed to an appreciable extent beyond portal-of-entry (POE) to
distal tissues/organs based on the currently available experimental
evidence. The sensory irritation is a local effect at POE that may
progress to adverse effects under repeated and prolonged consumer
exposure scenarios at POE. Therefore, the Agency could consider using
sensory irritation as an end point for Points of Departure (POD) as a
treatment effect that would protect against all downstream events
including a carcinogenic response.'' The conclusion of the SACC is
consistent with conclusions previously used by EPA in the 2008
Registration Eligibility Decision and other international bodies. For
example, Health Canada (2005, p. 5) states that ``Formaldehyde-induced
carcinogenicity appears to be a consequence of proliferative
regeneration following cytotoxicity, and the risk of cancer associated
with formaldehyde levels sufficiently low to prevent irritation and
inflammatory responses appears therefore to be negligible.''
WHO (2010) (Ref. 24) notes that ``Increased cell proliferation due
to cell damage is considered a key mechanism for the development of
nasal malignancies following exposure to formaldehyde. Overall, indoor
air effects of formaldehyde are expected to be limited to the site of
contact, generally the nasal and upper airways. Increasing cell
proliferation in the nasal mucosa of rats occurs at concentrations at
and above 2.5 mg/m\3\ formaldehyde. The no-observed-adverse-effect
level (NOAEL) for cell proliferation is 1.25 mg/m\3\ for long-term
exposures. Thus, a threshold approach to setting a guideline for cancer
effects is appropriate'' (p. 141). Similarly, the SACC stated that
``the majority of the information presented in session did not favor an
IUR approach and rather supported a threshold approach'' (SACC report
p. 22) (Ref. 12).
The SACC also stated that ``Although the Mueller et al. (2014)
study is an acute duration study, formaldehyde does not accumulate in
the body and Habers' Law does not apply for formaldehyde. Thus, use of
this study may be appropriate for setting a POD for chronic exposures''
(p. 58). OCSPP notes that the NOAEL for cytotoxicity and cell
proliferation identified by WHO of 1.25 mg/m\3\ for long-term exposures
in rats is 1.25 mg/m\3\ (equivalent to approximately 1 ppm of
formaldehyde) and they further state that ``In humans, no excess
nasopharyngeal cancer has been observed at mean exposure levels at or
below 1.25 mg/m\3\''. Health Canada also described the
histopathological effects such as ``hyperplasia, squamous metaplasia,
inflammation, erosion, ulceration, and disarrangements in the nasal
cavity at concentrations of 3.7 mg/m\3\ and above (NOAEL 1.2 mg/m\3\).
These histopathological effects appear to be a function of the
formaldehyde concentration in inhaled air rather than of the cumulative
dose.'' As such, the POD of 0.3 ppm is protective of effects for all
durations, including cancer. However, if human exposure occurs above
0.3 ppm for a sustained, long-term duration, there is potential for
cancer to develop.
Consistent with the recommendations from the SACC and noting
consistency with the science relied upon by other international bodies,
OCSPP is proposing that the best available science supports using the
revised draft acute inhalation POD of 0.3 ppm as protective of all
durations and inhalation hazards, including cancer, for the Draft
Memorandum. Consistent with this approach, and OCSPP's understanding of
the MOA of formaldehyde in the human body, OCSPP is also no longer
relying on the EPA IRIS RfC or IUR.
2. Weight of Scientific Evidence Conclusions for the Revised Draft
Acute Inhalation POD and UF
As described earlier in this Notice, based on the weight of
scientific evidence and informed by the best available science, OCSPP
is confident in the following determinations for risk assessment/risk
evaluation of formaldehyde:
an acute inhalation POD of 0.3 ppm is appropriate as the
critical effect to protect for all other potential hazards, including
cancer;
the acute inhalation POD can be applied to all durations
of exposure (including chronic and cancer) and all populations,
including occupational scenarios; and
a total UFH of 1 is appropriate.
For the Draft Memorandum, OCSPP is only including the MOE
calculations for acute (15-minute) inhalation exposure. Based on the
scientific evaluation presented herein, OCSPP proposes to rely on the
acute exposure scenarios for determinations of unreasonable risk. Given
the MOA of formaldehyde, chronic non-cancer and cancer health effects
are not expected if EPA is protecting for acute exposure and effects.
Previously estimated chronic exposure values for occupational,
consumer, and general population pathways remain in the risk evaluation
for formaldehyde. It is important to note that acute exposure was
assessed for all COUs and associated exposure scenarios in the risk
evaluation for formaldehyde and considered in this Draft Memorandum.
There are no exposure scenarios where only chronic exposure was
assessed in the risk evaluation for formaldehyde. Because the acute
risk estimates are protective of risk presented by chronic exposures,
EPA is using the acute risk estimates presented in this Draft
Memorandum to identify COUs that contribute to the unreasonable risk of
formaldehyde. Repeated or sustained long-term exposures to formaldehyde
above the revised draft POD increases the potential for chronic effects
including cancer.
3. Revised Draft Risk Calculations Resulting in Substantial Change
For COUs that the Agency found significantly contribute to the
unreasonable risk presented by formaldehyde in the Risk Evaluation for
Formaldehyde, the revised POD and corresponding uncertainty factor
impacts five COUs for workers where the central tendency or high-end
inhalation estimate no longer exceeds the benchmark. These COUs are
shown in Table 2.
In addition, three COUs would have central tendency and high-end
inhalation estimates for ONUs that no longer show risk above the
benchmark. These estimates are shown in Table 3.
4. Revised Draft Unreasonable Risk Determination for Formaldehyde
EPA previously determined that formaldehyde presents an
unreasonable risk of injury to human health under the COUs. The Agency
also determined that the unreasonable risk to human health presented by
formaldehyde is due to (1) non-cancer effects in workers and consumers
from acute dermal and inhalation exposures, and (2) cancer effects in
workers from long-term inhalation exposure (90 FR 316 (FRL-11608-04-
OCSPP)). EPA did not identify risk of injury to the environment that
would contribute to the unreasonable risk determination for
formaldehyde.
OCSPP maintains its determination that high and prolonged
inhalation exposures to formaldehyde can lead to cancer in humans.
However, OCSPP has concluded that acute sensory irritation is more
sensitive than cancer and therefore health-protective. Specifically,
the air concentrations that cause sensory irritation are lower than
those that
[[Page 55732]]
trigger early toxicological events, such as inflammation, cytotoxicity,
hyperplasia, squamous metaplasia, and increased cell proliferation in
the nasal mucosa of rats, which are involved in cancer development. In
other words, developing cancer from inhalation exposure of formaldehyde
requires concentrations several times higher than EPA's acute
inhalation POD, sustained over weeks to years. Thus, if an acute risk
of concern is identified, then there is also a potential concern for
cancer when exposures are higher and sustained.
Risk management efforts to reduce risk from acute inhalation risk
will address any potential risks from chronic exposures, including
cancer. Consistent with the statutory requirements of TSCA section
6(a), EPA will propose risk management regulatory actions to the extent
necessary so that formaldehyde no longer presents an unreasonable risk
under the COUs. The Agency expects to focus its risk management action
on the TSCA COUs that significantly contribute to the unreasonable
risk. However, it is important to emphasize that, under TSCA section
6(a), EPA is not limited to regulating the specific activities found to
contribute significantly to unreasonable risk and may select from among
a suite of risk management approaches based on requirements in section
6(a) related to manufacture (including import), processing,
distribution in commerce, commercial use, and disposal as part of its
regulatory options to address the unreasonable risk. As a general
example, EPA may regulate upstream activities (e.g., processing,
distribution in commerce) to address downstream activities (e.g.,
consumer uses) contributing significantly to unreasonable risk--even if
the upstream activities do not contribute significantly to the
unreasonable risk.
The determination that formaldehyde presents an unreasonable risk
of injury to human health would not change as a result of the risk
estimates used in this Draft Memorandum, and the same COUs would
continue to significantly contribute to the unreasonable risk for
formaldehyde as outlined in the Revised Draft Unreasonable Risk
Determination of the Risk Evaluation for Formaldehyde available in the
docket (EPA-HQ-OPPT-2018-0438). Although there are some changes to the
inhalation estimates, as noted above in Section II.C.4, dermal risk
findings for these COUs remain unchanged and continue to contribute to
unreasonable risks for these COUs.
Because the acute inhalation risk estimates, using an acute POD of
0.3 ppm and UF of 1, are protective of risk presented by chronic
inhalation exposures, the Agency intends to utilize the risk estimates
in the Draft Memorandum to safeguard against potential risk for all
inhalation exposure durations and effects, including cancer. Table S2-1
Supporting Basis for the Revised Draft Unreasonable Risk Determination
for Human Health (Occupational Conditions of Use) and Table S2-2
Supporting Basis for the Revised Draft Unreasonable Risk Determination
for Human Health (Consumer Conditions of Use) (Ref. 28) replace Table
2-1 and Table 2-2 of the Revised Draft Unreasonable Risk Determination
of the Risk Evaluation for Formaldehyde available in the docket (EPA-
HQ-OPPT-2018-0438). The POD in the Draft Memorandum identifies five
COUs that no longer indicate unreasonable risk for workers due to
inhalation:
Inhalation exposure route for workers no longer contribute
to the unreasonable risk for the COU, Oxidizing/reducing agent;
processing aids, not otherwise listed;
Inhalation exposure route for workers no longer contribute
to the unreasonable risk for the COU, Lawn and garden products;
Inhalation exposure route for worker no longer contribute
to the unreasonable risk for the COU, Adhesives and sealant chemicals
in wood product manufacturing; plastic material (including structural
and fireworthy aerospace interiors); construction (including roofing
materials); paper manufacturing;
Inhalation exposure route for worker no longer contribute
to the unreasonable risk for the COU, Recycling; and
Inhalation exposure route for worker no longer contribute
to the unreasonable risk for the COU, Laboratory chemicals.
The exact risk estimates for these inhalation routes can be found
in the docket accompanying this Notice. Additional scenarios where the
central tendency estimates are now above the benchmark include the
following:
Inhalation exposure route for ONUs no longer contribute to
the unreasonable risk for the COU, Adhesives and sealant chemicals in
wood product manufacturing; plastic material (including structural and
fireworthy aerospace interiors); construction (including roofing
materials); paper manufacturing;
Inhalation exposure route for worker no longer contribute
to the unreasonable risk for the COU, Recycling.
Inhalation exposure route for worker no longer contribute
to the unreasonable risk for the COU, Laboratory chemicals.
Because the revised acute inhalation POD of 0.3 ppm is protective
of all durations and inhalation hazards, including cancer, EPA
anticipates focusing risk management actions related to inhalation on
addressing risk from acute inhalation exposures.
For more information about the EPA's process for ensuring the
safety of existing chemicals, go to https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/how-epa-evaluates-safety-existing-chemicals.
Table 1--Key Human Studies Used To Evaluate Peak Air Concentrations of
Formaldehyde Associated With Sensory Irritation
------------------------------------------------------------------------
Exposure
Source concentrations Effects
------------------------------------------------------------------------
Kulle et al. (1987) (Ref. 15); I: 0.0, 0.5, 1.0, NOAEL = 0.5 ppm
Kulle (1993) (Ref. 29). 2.0 ppm, 2.0 ppm (0.62 mg/m\3\);
exercise; II: LOAEL = 1.0 ppm
0.0, 1.0, 2.0 (1.23 mg/m\3\)
ppm, 2.0 ppm for mild to
exercise; I: 0, moderate eye
0.62, 1.23, 2.46, irritation; BMC =
mg/m\3\; II: 0, 0.69 ppm (0.85 mg/
1.23 3.69 mg/m\3\. m\3\); BMCL =
0.502 ppm (0.617
mg/m\3\).
Andersen and M[oslash]lhave 0.24, 0.4, 0.81, During first 2
(1983) (Ref. 16); Andersen 1.61 ppm; 0.3, hours, no
(1979) (Ref. 30). 0.5, 1.0, 2.0 mg/ reported
m\3\. irritation
discomfort to
0.24 or 0.4 ppm
but discomfort to
0.81 and 1.61 ppm
within the first
hour. During
remaining 3 hours
exposure,
discomfort
reported at the
0.24 and 0.4 ppm
exposure levels.
[[Page 55733]]
Lang et al. (2008) (Ref. 14).... 0, 0.15, 0.3, 0.5 NOAEL = 0.5 ppm
ppm; 0.3/0.6, 0.5/ continuous (0.62
1.0 ppm peaks (0, mg/m\3\) and 0.3
0.3, 0.5 ppm with ppm with peak 0.6
EA); 0, 0.19, ppm (0.37/0.74 mg/
0.37, 0.62 mg/ m\3\); LOAEL =
m\3\; 0.37/0.74, 0.5 ppm with
0.62/1.23 mg/m\3\ peaks of 1 ppm
peaks (0, 0.37, (0.62/1.23 mg/
0.62 mg/m\3\ with m\3\) for
EA). blinking
frequency,
conjunctival
redness, eye and
nasal irritation,
and olfactory
symptoms.
Mueller et al. (2013) (Ref. 13). 0, 0.5, 0.7 ppm; At 0.3/0.6 ppm,
0.3/0.6 ppm increase in
peaks; 0.4/0.8 reported
ppm peaks; 0, irritation in
0.62, 0.86 mg/ hypersensitive
m\3\; 0.37/0.74 individuals. 0.4/
mg/m\3\; 0.49/ 0.8 ppm increase
0.98 mg/m\3\. in reported
irritation in
hypersensitive
individuals and
tear film break-
up time. 0.7 ppm
statistically
significant
increase in nasal
flow in
hypersensitive
males. For
hyposensitive
males: 0.4/0.8
ppm and 0.5 ppm
increase in tear
film break-up
time.
------------------------------------------------------------------------
NOAEL = no-observed-adverse-effect level; LOAEL = lowest-observed-
adverse-effect level; BMC = benchmark concentration; BMCL = benchmark
concentration level (lower 95 percent confidence limit).
Table 2--Acute MOE Calculations for Workers Where Central Tendency Risk or High-End Risk Is No Longer Below the
Benchmark for Workers or Occupational Non-Users
----------------------------------------------------------------------------------------------------------------
Draft Risk
supplement Draft evaluation Risk
central supplement central evaluation
COU tendency MOE high-end MOE tendency MOE high-end MOE
for acute for acute for acute for acute
inhalation (UF inhalation (UF inhalation (UF inhalation (UF
= 1) = 1) = 3) = 3)
----------------------------------------------------------------------------------------------------------------
Lawn and garden products........................ 7.18 1.77 11.9 2.95
Oxidizing/reducing Agent........................ 3.24 1.31 5.40 2.18
Adhesives and sealant chemicals in wood product 2.00 0.10 2.3 0.20
manufacturing; plastic material (including
structural and fireworthy aerospace interiors);
construction (including roofing materials);
paper manufacturing............................
Recycling....................................... 1.38 0.51 2.31 0.85
Laboratory chemicals............................ 1.98 0.10 1.99 0.23
----------------------------------------------------------------------------------------------------------------
Table 3--Acute MOE Calculations for ONUs Where Central Tendency Risk Is No Longer Below the Benchmark
----------------------------------------------------------------------------------------------------------------
Draft Risk
supplement Draft evaluation Risk
central supplement central evaluation
COU tendency MOE high end MOE tendency MOE high end MOE
for acute for acute for acute for acute
inhalation (UF inhalation (UF inhalation (UF inhalation (UF
= 1) = 1) = 3) = 3)
----------------------------------------------------------------------------------------------------------------
Laboratory chemicals............................ 1.99 0.232 1.19 0.14
Recycling....................................... 1.38 0.51 2.31 0.85
Adhesives and sealant chemicals in wood product 1.62 0.46 2.70 0.76
manufacturing; plastic material (including
structural and fireworthy aerospace interiors);
construction (including roofing materials);
paper manufacturing............................
----------------------------------------------------------------------------------------------------------------
III. Request for Comment
EPA seeks feedback on the Draft Memorandum and associated
documents, copies of which are available in the docket, and encourages
all potentially interested parties, including individuals, governmental
and non-governmental organizations, non-profit organizations, academic
institutions, research institutions, and private sector entities to
comment on the draft documents. To the extent possible, the Agency asks
commenters to please cite any public data related to or that support
comments provided, and to the extent permissible, describe any
supporting data that is not publicly available. EPA is not seeking peer
review for the Draft Memorandum as it relies extensively on multiple
existing and relevant peer review reports (Ref. 10, Ref. 12, and Ref.
18).
EPA welcomes specific input on each section of the Draft Memorandum
and related supported documents. The following information provided
will also be considered for risk management of formaldehyde:
Personal protective equipment (PPE) use, including the
type of PPE worn for different workplace activities and task durations
under the COU, circumstances where it may not be practicable for
potentially exposed persons to wear PPE, and feasibility of exposure
reduction to formaldehyde sufficient to address the unreasonable risk,
including associated monitoring practices to assess exposure
reductions;
Dermal and respiratory workplace controls, such as
eliminating dermal contact, engineering controls, and administrative
controls that could address the unreasonable risk;
[[Page 55734]]
Emission factors and weight fractions for commercial and
consumer products or articles along with the respective uses and
applications, and threshold or de minimus concentrations in products or
articles.
IV. Next Steps
EPA will consider comments received on the Draft Memorandum and
associated documents and announce the availability of the Updated Final
Risk Calculation Memorandum and Revised Final Risk Evaluation for
Formaldehyde Under the Toxic Substances Control Act (TSCA), if
warranted. Under TSCA section 6, EPA must use the final risk evaluation
as a basis to determine, based on the weight of scientific evidence,
whether or not the chemical presents an unreasonable risk to health or
the environment under the chemical's COUs. This includes risks to
subpopulations who may be at greater risks than the general population,
such as children and workers. TSCA prohibits EPA from considering non-
risk factors (e.g., costs/benefits) during risk evaluation.
If at the end of the risk evaluation process, EPA determines that a
chemical presents an unreasonable risk to health or the environment,
the chemical must immediately move to risk management action under TSCA
section 6(a). EPA is required to implement, via regulation, regulatory
restrictions on the manufacture (including import), processing,
distribution, use or disposal of the chemical to eliminate the
identified unreasonable risk. The Agency is given a range of risk
management options under TSCA, including labeling, recordkeeping or
notice requirements, actions to reduce human exposure or environmental
release, and a ban of the chemical or of certain uses. Like the
prioritization and risk evaluation processes, there is an opportunity
for public comment on any proposed risk management actions.
For more information about the TSCA risk evaluation process for
existing chemicals, go to https://www.epa.gov/assessing-and-managing-chemicals-under-tsca.
V. References
The following is a listing of the documents that are specifically
referenced in this Notice and other relevant risk evaluation documents.
The docket includes these documents and other information considered by
EPA, including documents that are referenced within the documents that
are included in the docket, even if the referenced document is not
physically located in the docket.
1. Executive Order 14303. Restoring Gold Standard Science. Federal
Register (90 FR 22601 May 29, 2025).
2. U.S. EPA. (2020). Use Report for Formaldehyde (CAS RN 50-00-0).
Docket ID: EPA-HQ-OPPT-2018-0438.
3. EPA. High-Priority Substance Designations Under the Toxic
Substances Control Act (TSCA) and Initiation of Risk Evaluation on
High-Priority Substances; Notice of Availability. Federal Register.
84 FR 71924, December 30, 2019 (FRL-10003-15).
4. EPA. Draft Scopes of the Risk Evaluations to be Conducted for
Seven Chemical Substances under the Toxic Substances Control Act.
Federal Register. 85 FR 22733, April 23, 2020 (FRL-10008-05).
5. EPA. Final Scopes of the Risk Evaluations to Be Conducted for
Twenty Chemical Substances Under the Toxic Substances Control Act;
Notice of Availability. Federal Register. 85 FR 55281, September 4,
2020 (FRL-10013-90).
6. EPA. Formaldehyde; Draft Risk Evaluation Peer Review by the
Science Advisory Committee on Chemicals (SACC); Notice of
Availability, Public Meetings, and Request for Comment. Federal
Register. 89 FR 18933, March 15, 2024 (FRL-11608-03-OCSPP).
7. EPA. Formaldehyde; Risk Evaluation Under the Toxic Substances
Control Act (TSCA); Notice of Availability. Federal Register. 90 FR
316, Jan 3, 2025 (FRL-11608-04-OCSPP).
8. U.S. EPA. (2022). Draft Toxicological Review of Formaldehyde--
Inhalation. (EPA/635/R-21/286a). Washington, DC: Center for Public
Health and Environmental Assessment, Office of Research and
Development.
9. U.S. EPA. (2024a). IRIS Toxicological Review of Formaldehyde
(Inhalation). (EPA/635/R-24/162AF). Washington, DC: Center for
Public Health and Environmental Assessment, Office of Research and
Development. https://iris.epa.gov/static/pdfs/0419tr.pdf
10. NASEM. (2023). Review of EPA's 2022 Draft Formaldehyde
Assessment. Washington, DC. https://nap.nationalacademies.org/catalog/27153/review-of-epas-2022-draft-formaldehyde-assessment
11. HSRB. (2022). Report of the U.S. Environmental Protection Agency
Human Subjects Review Board. https://www.epa.gov/system/files/documents/2023-03/HSRB%20Oct%20Report%20Final.pdf
12. U.S. EPA. (2024b). Science Advisory Committee on Chemicals
meeting minutes and final report No. 2024-01 (Docket ID: EPA-HQ-
OPPT-2023-0613)--A set of scientific issues being considered by the
Environmental Protection Agency regarding: Peer review of the 2024
Draft Risk Evaluation for Formaldehyde, May 20-23, 2024. (No. 2024-
01). Washington, DC. https://www.regulations.gov/document/EPA-HQ-OPPT-2023-0613-0298
13. Mueller, JU; Bruckner, T; Triebig, G. (2013). Exposure study to
examine chemosensory effects of formaldehyde on hyposensitive and
hypersensitive males. Int Arch Occup Environ Health 86: 107-117.
http://dx.doi.org/10.1007/s00420-012-0745-9
14. Lang, I; Bruckner, T; Triebig, G. (2008). Formaldehyde and
chemosensory irritation in humans: A controlled human exposure
study. Regul Toxicol Pharmacol 50: 23-36. http://dx.doi.org/10.1016/j.yrtph.2007.08.012
15. Kulle, TJ; Sauder, LR; Hebel, JR; Green, DJ; Chatham, MD.
(1987). Formaldehyde dose-response in healthy nonsmokers. J Air
Pollut Control Assoc 37: 919-924. http://dx.doi.org/10.1080/08940630.1987.10466285
16. Andersen, I; M[oslash]lhave, L. (1983). Controlled human studies
with formaldehyde. In JE Gibson (Ed.), Formaldehyde toxicity (pp.
154-165). Washington, DC: Hemisphere Publishing.
17. HSRB. (2023a). Report of the U.S. Environmental Protection
Agency Human Subjects Review Board. https://www.epa.gov/system/files/documents/2023-05/HSRB%20May%20Final%20Agenda%205-16-23.pdf
18. HSRB. (2023b). Report of the U.S. Environmental Protection
Agency Human Subjects Review Board. https://www.epa.gov/scientific-leadership/hsrb-july-26-2023
19. Hanrahan, LP; Dally, KA; Anderson, HA; Kanarek, MS; Rankin, J.
(1984). Formaldehyde vapor in mobile homes: A cross-sectional survey
of concentrations and irritant effects. Am J Public Health 74: 1026-
1027. http://dx.doi.org/10.2105/ajph.74.9.1026
20. U.S. EPA. (2024c). Human Health Hazard Assessment for
Formaldehyde. Washington, DC: U.S. Environmental Protection Agency,
Office of Pollution Prevention and Toxics. https://www.regulations.gov/docket/EPA-HQ-OPPT-2018-0438
21. U.S. EPA. Formaldehyde; Draft Risk Evaluation Peer Review by the
Science Advisory Committee on Chemicals (SACC); Notice of
Availability, Public Meetings and Request for Comment. Federal
Register. 89 FR 18933, March 15, 2024 (FRL-11608-03-OCSPP).
22. Shusterman, D; Matovinovic, E; Salmon, A. (2006). Does Haber's
law apply to human sensory irritation [Review]. Inhal Toxicol 18:
457-471. http://dx.doi.org/10.1080/08958370600602322
23. NRC. (2001). Standing Operating Procedures for Developing Acute
Exposure Guideline Levels (AEGLs) for hazardous chemicals.
Washington, DC: National Academies Press. http://dx.doi.org/10.17226/10122
24. WHO. (2010). Guidelines for indoor air quality: Selected
pollutants. Geneva. http://www.euro.who.int/__data/assets/pdf_file/0009/128169/e94535.pdf
[[Page 55735]]
25. ECHA. (2019). Annex XV Restriction Report, Proposal for a
Restriction: Formaldehyde and Formaldehyde Releasers. Helsinki,
Finland: European Union, European Chemicals Agency. https://echa.europa.eu/documents/10162/13641/rest_formaldehyde_axvreport_en.pdf/2c798a08-591c-eed9-8180-a3c5a0362e37
26. UBA. (2016). Zur Frage eines Asthma ausl[ouml]senden bzw.
verschlechternden Potenzials von Formaldehyd in der Innenraumluft
bei Kindern [Review]. Bundesgesundheitsblatt Gesundheitsforschung
Gesundheitsschutz 59: 1028-1039. http://dx.doi.org/10.1007/s00103-016-2388-6
27. Liu, K; Huang, F; Hayward, SB; Wesolowski, J; Sexton, K. (1991).
Irritant effects of formaldehyde exposure in mobile homes. Env
Health Persp 94: 91-94.
28. U.S. EPA. (2025). Supporting Basis for the Revised Draft
Unreasonable Risk Determination for Formaldehyde.
29. Kulle, TJ. (1993). Acute odor and irritation response in healthy
nonsmokers with formaldehyde exposure. Inhal Toxicol 5: 323-332.
http://dx.doi.org/10.3109/08958379308998389
30. Andersen, I. (1979). Formaldehyde in the indoor environment--
health implications and the setting of standards. In PO Fanger; O
Valbjorn (Eds.), Indoor Climate: Effects on Human Comfort,
Performance, and Health in Residential, Commercial, and Light-
Industry Buildings (pp. 65-87). Copenhagen, Denmark: Danish Building
Research Institute.
Authority: 15 U.S.C. 2601 et seq.
Dated: November 28, 2025.
Nancy B. Beck,
Principal Deputy Assistant Administrator, Office of Chemical Safety and
Pollution Prevention.
[FR Doc. 2025-21776 Filed 12-2-25; 8:45 am]
BILLING CODE 6560-50-P