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FORMALDEHYDE
The Conquer Product Safety Commission's
Risk Assessment for Formaldehyde
William M. Stigliani
A. BACKGROUNl) AMB CONTEXT
1 ~ Describe the chemical and i ts uses .
Formaldehyde is a colorless, flammable gas with a strong, pungent
odor. It can form explos ive :aixtures wi th air and oxygen. As an
important industrial chemical of ma jor commercial use, formalde-
byde is found throughout the environment . In outdoor air, it can
originate from many sources such as incinerators, photochemical
smog, and engine exhaust. Atmospheric levels of formaldehyde have
been reported to range from less than 0.005 ppm to 0.06 ppm near
industrial outlets or in areas of heavy smog. Corkers who smoke
are exposed to additional levels of formaldehyde, since cigarette
smoke contains an mucl, as 40 ppm of formaldehyde by volume. Thus,
an individual who smokes a pack of cigarettes ~ day would inhale
0.38 ma, whereas occupational exposure to formaldehyde at 3 ppm
could result in a daily intake of 29.0 ma.
Production and Uses
l
Formaldehyde is usually manufactured by reacting methanol vapor
and air over a catalyst (chemical initiator). This results in
formaldehyde containing trace amounts of methanol and formic
acid. Formaldehyde is sold mainly as an aqueous (water-based)
solution called formalin, which is 37: to 50% formaldehyde by
NOU: Thin case s Judy describes assessment procedures and summarizes
issues and interpretations raised by others, but it is not intended to
present independent pos itions or interpretations on either scienti fic
or policy matters. The case has been reviewed by individuals outside
the study project who are directly familiar with the federal analyses
ant decisions described; however, responsibility for the paper rests
with the author, and it does not necessarily reflect the judgment of
the Committee on the Institutional Means for Assessment of Risks to
Public Health or the National Research Council. It has not been subs
jected to internal review procedures that apply to reports prepared by
NRC committees.
1
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2
weight. It is also used in its solid form as paraformaldehyde and
s-trioxane . The U. S. produced about 6.4 billion pounds of aqueous
formaldehyde in 1978. Most of this quantity was used
domestically. The U. S. consumption of formaldehyde by the year
1983 will likely exceed 7.5 billion pounds .
Half of the formaldehyde produced is used to produce synthetic
resins such as urea- and phenol-formaldebyde res ins . These resins
are used primarily as adhesives when making particleboard, fibers
board, and plywood. Urea-formaidehyde concentrates are also used
in various coating processes, in paper products, and in malting
foams for thermal insulation. The textile industry uses formal-
dehyde for producing creaseproof, crushproof, flame resistant, and
shrinkproof fabrics. Acetal resins, made from formaldehyde, are
used to mold plastic parts for automobiles, home appliances, hard-
ware, and garden and sporting equipment O Formaldehyde is used in
some medicines because it modifies and reduces the toxicity of
viruses, venoms, and irritating pollens. The use of formaldehyde
in embalming fluids is now required by all s Pate laws.
The widespread use of formaldehyde is due to its high
reactivity, colorless nature, purity in commercial forms and low
cost. In making other chemicals, it can link similar asked dis-
similar molecules together. In the paper industry, formaldehyde
and its derivatives impart wet strength, as well as shrink and
grease resistance. Leather and fur can be tanned 'oy formalde-
hyde. Formaldehyde is used in the photographic industry because
it hardens and insolubilizes the gelatin surfaces of f ilm and
papers.
Release of Formaldehyde from Urea-Formaldebyde
Foam Insulation (UFFI) .
UFFI is a cellular plastic product used as a thermal insulation
criteria ~ O The product is manufactured at the job ~ ite by feeding,
generally, pressurized air along with two 1 iquid chemicals-~a urea-
formaldehyde based (or urea-based) res in and a foaming agent--
through ~ foam equipment system. The product that resul, s from
this reactive mixture has a starring cream~tike consistency and is
usually pumped through relatively smal 1 holes into the wal Is of
standing structures. After the llFFI is inside the wall, the
insulation becomes firm or self-supporting. Formaldehyde that has
not reacted with oilier chemicals after installation can eventually
be released as formaldehyde gas. lithe likelihood of release of
formaldehyde depends on factors such as temperature, humidity,
foam formulation, architectural cons iderat ions, and ins tat let ion
techniques .
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3
2. Describe how the question of risk was elevated to the
agency agenda*.
Irritation ant Sens it ization
Initial focus of attention to the possible health problems of UFFI
began in October 1976, when the Metropolitan Denver District
Attorney's Consumer Office filed a petition, requesting the
Conquer Product Safety Commission (CPSC) to develop a safety
s tandard for certain types of home insulation products, including
UFFI. The petition claimed that there is an unreasonable risk of
injury or irritation associated with UFFI. Over the next three
years, several thousand consumer complaints related to irritation
and sensitivity from formaldehyde released from UFFI were filed
with CPSC.
After considering information compiled by staff, the
Commission decided, in March 1919, to defer a decision on the part
of the petition relating to UFFI and instructed the staff to
evaluate additional information on possible means of addressing
the alleged unreasonable risk of injury (44 FR 12080~. In
addition, in May 1979, CPSC began the sponsorship of ~ National
Academy of Sciences s tudy which "xamined the acute and s ens i-
tization effects due to formaldehyde. The final report, issued in
March 198D, stated that "an yet there is no evidence of a
population threshold for the irritant effects of formaldehyde in
humans. " lathe NAS committee also recommended that levels of
formaldehyde be held at the "lowest practical concentration. " The
latter suggestion may Cadre been influenced to some extent by a
preliminary report to CPSC in October 1979 that formaldehyde
caused cancer in rats.
In November 1919, staff again briefed the Commission on the
s talus o f information gathered concerning formaldehyde toxicity
and UFFI. Follow~up investigation of some of the reported
complaints indicated a range of severity of reported reactions
varying from short-term discomfort to alleged chronic impairment,
such as loss of visual acuity, reduction in lung function, and
sensitization to other sources of formaldehyde.
As a results of these briefings, the Commission decided to
hold public hearings to obtain additional information on safety
ant health problems associated with UFFI (44 FR 69578~. The
Commission held public hearings in Portland, Oregon; Atlanta,
Georgia; Minneapolis, Minnesota; and Hartford, Connecticut from
December 19799 through February 1980. Consumers, industry
representatives, state and local government officials, scientists,
and others testified a t the hearings as to their experiences with
UFFI and formaldehyde. Based on the information obtained in these
hearings an well as the consumer complaints and medical and
* This case study describes activities only through April 1982.
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scientific information obtained beforehand, the Commission9 on
June TO, 1980, proposed a rule requiring manufacturers of UFFI to
give specified performance and technical information to purchasers
to alert them about the possible adverse health effects associated
with the release of formaldehyde gas from the product after it is
installed in residences (45 FR 39434~.
Carcinogenic Risk
In October 1979, representatives of the Formaldehyde Institute,
an ir~dus try bate association, reported to CPSC the preliminary
findings from a careinogenicity study sponsored by the Chemical
Industry Institute for Toxicology (CTIT). This study showed that
rats exposed to 15 ppm of formaldehyde developed squamous cet1
care inoma o f the nose .
In January i9809 an Interagency Regulator Liaison Group
(IRLG) task force including six pathologists visited CIIT to
obtain additional information concerning the longs study and
to verify the findings a In a report prepared in February 1980,
the group concurred, in general, with the CIIT observations 9
diagnoses, and interpretations.
As the ClIT experiment progressed and more data became
available, the need for a full review of the potential health
risks of cancer and other genetic diseases to toucans from chronic
exposure to formaldehyde became evident. In April 1980, CPSC, in
conjunction with the National Toxicology Program (NTP) formed the
Formaldehyde Parcel, consisting of 16 federal scientists g charged
-title reviewing and evaluating the avai late Le published and un-
published information including the ongoing CIIT study. In its
final report to CPSC in November 1980, the panel concluded that it
would be "prudent to regard formaldehyde as posing a carcinogenic
risk to 'numans. "
Based in part on the findings of the Formaldehyde Panel 9 as
well as on its determination of the irritating and sensitizing
effects of formaldehyde g CPSC called for a proposed ban of UFFI in
February 19810 The rule was made final in April 19632e
3. Under what statutes and agency ; urisdiction does ache chemical
fall? What statutory tests governed the decision?
.
The ban of t3FFI falls under the jurisdiction of two possible CPSC
statutes These are: Section ~ of the Consumer Product Safety
Act (CPSA) and Section 2( q) ( 1) (B.) of the Federal Hazardous
Substances Act (FHSA). The Commission chose to regulate under the
CPSA for two reasons. First, under the MESA, the Commission
lacked the authority to cover products installed in nonresidential
applications such as schoolsO Secondly because of the complex
and lengthy nature of the rulemaking proceeding that would be
required under the FHSA, the Commission believed it would be in
the public interest to regulate this product under the CPSA.
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5
under Section ~ of the CESA, there are two criteria that must
be met before the Commission can issue a proposed ban. There are:
(1) The consumer product is being, or will be, distributed in
commerce and presents an unreasonable risk of injury; and
(2) No feasible standard under the Act, including require-
ments for warnings and instructions, would adequately protect
ache public from the unreasonable risk of injury associated
wi th the produc ~ .
In CPSC ' s judgment, unreasonable risk was demonstrated by the
irritant and sensitizing effects, and carcinogenic potential of
formaldehyde . Lee Commiss ion examined the existing information
concerning the feasibility of a standard and found that there was
no feasible standard, including labeling, that would adequately
protec t the pub kc .
In its finding that it was not possible to establish a
feasibility standard, CPSC denied ~ petition it received from the
Formaldehyde Institute on April 16, 1981, which requested that the
Commission issue a safety ~ tandard applicable to UFFI.
4. That was the decision schedule? Note any s tatutory
or other action deadlines.
October 19 76
Action: We Metropolitan Denver District Attorneys Consumer
Of Eice filed a petition to CPSC, requesting the Commission to
develop a safe ty standard for insulation products, including
U.F.F. I.
June 10, 1980
Action: CPSC issued a proposed rule to require manufacturers of
UFFI to give information to prospective purchasers deco alert them
to the possible adverse health effects associated with the release
of formaldehyde gas from the product.
Deadlines: Written comments to proposed rule to be submitted by
.
August L1, 1980.
(compliance to begin six weeks after publication of final rule.
November 20, 1980
Submiss ion of Formaldehyde Panel report to CPSC.
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6
February 5, 1981
Action: CESC issues a proposed rule to ban UFFI from residential,
commercial, and public buildings in the U.S.
CPS(: denies the leerier petition of October 19760
Deadl ines: Written cogent ~ to proposed rule to be submi tted by
April 6, 19810
Oral presentation by interested parties concerning proposed rule
to be presented Larch 20, 1981.
April 10, 1981
Action: The Formaldehyde Institute fi led a petition to CPSC,
requesting that the Cotillion issue a safety standard applicable
to IJFFI.
October 26, 1981
Completion of CPSC 9 S quantitative risk assessment.
April 2, 19~82
Action: CPSC issues a rule to ban ~FFI from residences and
schoo l ~ in the U ~ S a
CPSC withdraws proposed rule of June 10, 19800
CPSO denies Fo~aidehyde Institute petition of April 10, 1981
Deadlines: The bass is effective on or after August to, 1982 or
the day after the expiration of the 90 calendar day period of
continuing session of Congress following promulgation of the ban,
whichever date is later.
B IDENTIFICATION OF HAZA R33
O
(determining the presence or absence
of potential tonic effects)
1. What health endpoints were evaluated?
CPSC evaluated a wide range of potential adverse health ef fee ts
front fo~aidehyde exposure. Acute effects, such as irrita~eton of
the eyes9 nose and respiratory tract were examined9 as well as a
wide variety of other effects such as drowsiness, nausea and
headaches O
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?
Sensitization of certain individuals due to fo~=aideh~e
exposure was also addressed. CPSC was concerned about a small
segment of the population which could be susceptible to severe
reactions such as allergic dermititis and asthma.
Finally, CPSC reviewed the potential of formaldehyde to ~nduc
genetic disease. Ins effects on reproduction ant teratogenicity,
mutagenicity and carcinogenicity were reviewed and evaluated,
al though the main f ocus was on cancer.
2. What were the key data available for review?
(What additional data were sought? )
e
Prior to the release of preliminary data from the CITT study in
November 1979, CPSC was almost exclusively concerned with
potential acute effects and hypersensitivity caused by formal-
deh~rde exposure. Over the course of about three years, the
Commission had received over 2,000 consumer complaints of adverse
health effects from the release of formaldehyde gas from UFFI.
These complaints provided the CPSC witl, a readi ly available data
base Deco examine the effects of interest. The Commission staff
conducted follo~up investigations for over 200 of the complaints.
In addition, CPSC asked the National Academy of Sciences (NAS)
to conduct a study assessing the health effects of formaldehyde.
A final report to the Commission was completed in March 198Q. Two
other NAS studies Indoor Pollutants (1981) and Formaldehyde and
Other Aldehydes (1981) were available for review and evalua-
tion.
After November 1979, CPSC was also concerned with the
potential carcinogenic effect of formaldehyde. Review of the CIIT
rat study began while it was still in progress. In January 1980,
an I}lLO tack force was formed to verify the initial findings of
CIIT and to ~ eek further informa ~ion. In a report prepared in
February 1980, the group concurred in general with the CIIT
observations. In April 1980, CPSC, in conjunction with the
National Toxicology Program (NTP) formed the Formaldehyde Panel,
consisting of 16 federal scientists, to continue Else review of the
ongoing CIIT study. In addition, the Pane! was charged with
evaluating all available published and nonpublished literature
relating to other genotoxic endpoints. In November 1980, the
Panel reported its conclusion to CPSC that it is prudent to regard
formaldehyde as a human carcinogen.
Four other groups of scientists in separate reports endorsed
the opinion that formaldehyde should be viewed as if it were a
h''m~n carcinogen. The first was a NIOSH Current Intelligence
Bulletin. Another was a report based on a rat study conducted by
scientists at New York University. In a letter sent to CPSC by
Dr. A. Upton, professor and chairman of the New York University
Medical Center, the NYU study was cited as providing 'decisive
confirmation of the CIIT findings." The third was a report from a
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working group of the International Agency for Research OR Cancer
(IARC) in October 1981. A fourth group, in a report to the
American Cancer Society by the Environmental Cancer Information
Unit, chaired by I. J. Selikof f and E. C . Hammond (February 1981),
found that fo~aidebyde was an animal carcinogen and that human
exposures should be reduced or eliminated
There were some limited human studies on industry workers and
morticians. CESC found these to be inconclusive regarding their
ability to predict human carcinogenic effects. The same
conclusion was drawn by a working group of IARC.
3. Ah_ ~
background? Available analytic resources? )
Irritation and Sensing ivi ty
From the thousands of consumer complaints DISC rece ived, several
hundred were singled out for followed investigation by CPSC.
Part of the investigation consisted of answering a questionnaires
Questions were designed by staff epidemiologists and chemists In
addition, when the complainant was treated by a physician, the
doctor was contacted to obtain further details. Also, a medical
officer on the CPSC: staff reviewed the complaint file.
She NAS analysis of health effects of formaldehyde, which was
a key document in CPSC ' ~ a~se~:oent o ~ acute symptoms, was pert
formed by 13 medical doctors and client. They had expertise
in various areas including toxicology, epidemiology, and
dermatology .
Carcinogenic Effects
The GREG tack force that made the preliminary evaluation of the
CIIT study in January 1960 consisted of six pathologists
representing CPSC9 NIGHS, DOE, EPA and NCI as well as other health
scientists. The Formaldehyde Panel which made the final evaluso
tion of the CllT study for CPSC consisted of sixteen scientists
from various federal agencies including EPA, DOE, NCT, IDA, NIERS,
NIOSE, NCTR, and OSHA. All of these had Ph.D.s, Sc.D.s or M.D.s,
ant they represented expertise in the areas of carcinogenicity,
metabolism, teratology and reproduction, epidemiology,
mutagenicity, and risk analysis.
The CPSC staff reviewing the Eormaldebyde data in both of these
areas consisted of six Ph.D;s or DolteMe8. They hat backgrounds in
carcinogenicity, metabolism, mutagenicity, risk analysis and
toxicology, biochemistry and pathology a
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4. How was uncertainty described in reaching final interpreta-
tions ? Were cruc ial as gumptions made exo1 icit?
Irritation and Sensitivity
lathe identification of the effects of irritation and hyper-
sens itivity caused by formaldehyde exposure is quite certain.
Controlled Bean studies where small numbers of young healthy
adults were exposed to concentrations of for-`ualdebyde varying from
20 ppm to less than ~ pp~n for short periods provide the best
evidence . Be NAS s tudy on health ef fects of formaldehyde (March
1980) discusses these and other relevan~c evidence in detail.
There is some question as to whether studies on limited
populations are applicable to the general population. The NAS
study notes this limitation and enumerates the factors that might
lead to a wide range of individual susceptibility; e.g., health
status, genetic predisposition, age, pregnancy. Notwitlls~anding
these factors, the NAS report does caution that "responses
reported in controlled studies may occur at an increased rate in
the general population, because of the interaction between
formaldehyde and other irritants in the environment. " Finally,
NAS states: "Some of the factors might decrease susceptibility;
mos t may Increase fit.
The poss ible exit fence of a threshold to irritation and
hypersensitivity raises another point of uncertainty. The NAS
study states, "As yet, there is no evidence of a population
threshold for the irritant effects of formaldehyde in humans."
The NAS leaves this question unresolved but advised maintaining
"formaldehyde at the lowest practical concentration to minimize
adverse effects on public health. " By the time NAS committee
members wrote the final report, the preliminary results of the
CIIT study were known. This new information probably affected
their final recommendations.
Care inogenici ty
Since there are no definitive human studies to date for
carcinogenic effects of formaldehyde, its potential carcino-
genici ty in humans must be inferred from animal data. The lack of
direct evidence was clearly stated by the Formaldehyde Panel. The
Panel concluded that "definitive expe eiments exis t which demon-
strate the mutagenicity and carcinogenicity of formaldehyde under
laboratory conditions. " It further stated that "the data
presently availab le do not permit a direct assessment 0 f the
carcinogenicity of foe =aldehyde to man. " In reaching its final
determination it stated: "it is the conclusion of the Panel that
it is prudent to regard formalt~hyde as posing a carcinogenic risk
to humans . "
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5. What qualitative factors affected the weighting of data?
There mere two particular features of the CIIT study which the
Formaldehyde Panel weighed before reaching its conclusions O One
was the occurrence of a viral upper respiratory tract infection
(sialotacyoadenitis) in the test animals at twelve months of
exposure that lasted about one week. The virus event left open
the possibility that the infection served as a co-carcinogenic
effect contributing to the carcinoma response.
Me other feature was that the rats developed severe
irri tat ion in their nasal cavities due to formaldehyde exposure.
his symptom raised the question of whether irritation effects In
and of themselves could cause or contribute to a carcinogenic
response.
lye Formaldehyde Panel, in considering these two questions,
did cot completely discount their importance, but concluded that
it was unlikely that either could cause an experimental artifact.
With regard Deco the viral infection, the Panel report stated that
'tua~al tumors had probably already formed at the time of the
infection," thus casting doubt upon the possibility of ~
· O
co-care 1nogen~c response c
The Panel addressed the question of irritation by stating they
"found no evidence that the induc tion of irritation . O O is a
sufficient condition for the carcinogenic activity of an agents"
6. What inference options were used in the Razard
Identification step? Were they explicit and in accord
with any general guidelines?
Inference Options Used in Bazard Identification*
(1) Degree of confirmation of positive results) significance
. . .
Of negative results: The Formaldehyde Panel reached its
conch u lion b seed ~~ the positive CIIT rat study as well as
other supporting evidenced T.nis evidence included:
~ a) Me NYtJ rat study of Laskin et al . that demonstrated
a positive carcinogenic response from a different ~rain.
(b) Me demonstrated genotoxicity of formaldehyde
* The inference options cited here are drawn from Risk Assessment in
the Federal Government.~Managing the Process, NAS ( 1983), ppO 29-30.
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(c ~ Suggestive evidence from species other than the rat
and tissues other than the nasal epithelium; e.g., lesions
interpreted to be carcinomas _ situ induced in the oral
mucosa of rabbits.
Me Panel reviewed the known data for hamsters, which
apparently did not exhibit a carcinogenic response to
formaldehyde. This negative result did not appear to
influence the Panel's final conclusion, based on the positive
animal s tudies . **
(2) Evidence of different metabolic pathways between animals and
humans: The Formaldehyde Panel reviewed extensively the known
~-
data about for~aldehyde metabolism but did not reach any
conclusions about interspecies difference. lathe Panel did
recommend as future research, that "the pharmacokinetics of
formaldehyde and its interaction with target tissue should be
studied in several animal species. "
(3) Findings of tissue damage and other effects in the inter-
~ _
preta~ion of tumor data: The Formaldehyde Panel considered both
the irritation effects and the cytotoxic of feces of formaldehyde.
For irritation the Panel concluded that it was Inconceivable that
the 'irritant' effect of formaldebyde...may contribute to some
extent to the expression of its carcinogenic activity through a
mechanism enhancing the promoting or tumor growth s t age of
carcinogenesis. However, it must be added that our knowledge of
this type of effect is still quite inadequate and not directly
applicable to the reported carcinogenic ef fects of formaldehyde on
the nasal mucosa. "
Regarding cytotoxicity, the Panel noted that "most care inogens
have significant cytotoxic effects. Therefore, formaldehyde is
not an unusual case....In short, it is conceivable that the
cytotoxic effects of fo'-=aldebyde may play a part of its overall
carcinogenicity. "
(4) Use of short-term test data: As noted above, the Formal-
dehyde Panel used short-term tests demonstrating the genotoxic
effects of formaldehyde an supportive evidence for the carcino-
genic effects of formaldehyde.
-
** 'rhe Panel did cite a (as yet unpublished) report indicating that
formaldehyde might act an a tumor Enhancing agents' in the trachea
of hams ters ~ but acknowledged the s tudy was 1 imited ~
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Variations Across Agencies
Thus far, CPSG is the only agency to issue a final rule on
formaldehyde use. IN based this decision on a risk assessment
similar in many aspects to the EPA PRL-1 document which was
criticized by Dr. Todhur`~er irt his February 1O5 1982 memo to Ms.
Gorsuch. Even though the Todbunter memo does not specifically
address the CPSC risk assessment 9 the issues raised therein do
serve to highlight differences of interpretation of risk assess-
ment data between CPSC and EPA. I ~ should be noted that the
degree to which the two agencies differ increased significantly
with the advent of the new administration at EPA in the spring of
1981 ~ see Question B. tO) .
In specific terms, ])r. Todhunter states that, "Formaldehyde
appears, therefore, to exhibit considerable species specificity
with the rat, the most sensitive species so far tested. Concern
that formaldehyde gas may induce tumors in humans should be
tempered by this observation that formaldehyde c arc inogenicity
appears to have a high degree of species specificity and a strong
dependence on route of exposure." CPSC' s position is that the
strong evidence of carcinogenicity in rats provides strong
evidence of carcinogenicity in humans, especially in Light of the
limitations o f the negative studies .
Dr. Todbunter also argues that at low levels of exposure ( 1-2
ppm) formaldehyde may exhibit a toxicity much reduced from that
predicted by the 1 ineasized model ut il ized by CPSC O He sites
findings by CTIT to support thin argument. These are:
(1) Reversibility of byperpLastic and metaplastic
effects of formaldehyde at low exposure levels or short
exposure t ides;
(2) The presence of endogenous levels of formaldehyde
in tissue ranging from 3-12 ppm;
(3 ~ The absence of cytotoxie Of facts from formaldehyde
levels at or below LoO ppm in air;
(~) Evidence to sugges t that formaldehyde acts as a
promoter.
CPSC re jec ts the contention that Cheese arguments sugges t a
nonlinear dose-response relationship at low dose, with greatly
reduced risk at low levels of exposure. CPSC believes that
formaldehyde is both an initiator and a promoter and that the
reversibility and promotional aspect ~ points 1 and 4) do not argue
against linearity at low doses especially when the property of
initiation is CONS idered O CPSC further be lieves that tile absence
of cytotoxic effects at loO ppm has not been at all demonstrated;
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and that, nevertheless, the concept of cy~cotoxicity is not
relevant to the shape of the dose-re~ponse curve at low dose where
initiation and promotion aspects of formaldehyde are still likely
to be operating. Finally, CPSC believes the entogenous levels of
3012 ppm are also not derived from any existing data, and not
relevant to the argument. CPSC notes that virtually all formal-
dehyde in tissues is not free, but bound in a different chemical
fore with entirely different chemical and biological properties.
Another point of departure is interpretation of data on benign
tu~OtSo Dr. Todbun~er does not directly address the question of
benign tumor incidence in the formaldehyde rat study. He does
address the topic generically when suggesting a definition for the
term "serious. " (Part of the criteria for initiating Section 4( f)
is the determination of "serious or widespread harm. " ~
The concept of "serious" harm would have more utility
in the consideration of gene mutational events or birth
defects than in the case of cancer since malignant neo-
plasms in general are serious. Section 4( f) also draws a
distinction between benign and malignant growths by use
of the term "cancer" rallier than "tumors.''
The CPSC risk assessment did not consider benign tumors,
mainly because the information regarding their inc idence was not
reported to CPSC by CIIT at the time. CPSC 's risk assessment does
state, however, that inclusion of benign tumor data would lead to
an increas ed pred ic t ion o f ris k.
Another point of difference regarding the interpretation of
available epidemiologica1 data for formaldehyde. Dr. Todhunter
states, ''There is a limited but suggestive epidemiological base
which supports the notion that any human problem with formaldehyde
carcinogenicity may be of low incidence or undetectable. In would
not appear reasonable to say that a significant risk situation
exists from this data." CPSC, after reviewing epidemiological
evidence from written statements and oral presentations at public
meetings concluded that none of the epidemiological s tudies to
date were of ~uf ficient ~ tatistica1 sensitivity or qua L ity to draw
any valid inferences regarding the magnitude of carcinogenic risk
to humans. Scientists at NIOSH and a working group of [ARC
concurred wi th the CPSC evaluation.
The two agencies differ sharply on the levels of risk that
should trigger concern. Dr. Todhunter states, "In terms of
individual lifetime cancer risks, the various federal agencies do
not tend tco regulate risks of ~ x 10-5 or lower and tend to be
ambivalent about risks between 1 x 10-4 - 1 x 10-5. " He
stakes further [hat, "In OPTS, the relative risk range of 1 x
t`~~ to ~ x 10 or lower has been a low concern range in
general." CESC's estimated risk for inhabitants of UFFI
residences is 0.6 x 10 4 - 0.9 x 10-4. Also, in a proposed
rule regarding chemical compounds in food-producing animals, F1)A
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suggested ~ risk of 1 x 10 6 over a lifetime as a trigger for
regulatory action: "An increase in the level of risk to l in
10,000 might significantly increase human risk. It is difficult
to choose between ~ in ~ million and ~ in 10,000 but the agency
chose the more conservative number in the general interest of
protecting Furman t~ealth,'t (FDA, 1919~.
Finally, Dr. Tothunter states, "lathe results of the CIIT
bioassay are, however, sufficient to establish that formaldehyde
is a potential animal carcinogen with mode and degree of exposure
quite important to the outcome." CPSC's opinion is that forTeal-
dehyde is a definite animal carcinogen and should be a presumed
human carcinogen.
3. To the extent there were issu~s/concerns about questions of
silence 9 would tone outcome have been improved 'oy:
- A better system of in-house scientific review?
Review by an outside scientific organization?
- Coherent federal guidelines on carcinogenic risk assessment?
- Better agency guidelines on the performance of risk
assessment?
- Improved agency dec is ion procedures ?
In the view of the author of this case study, many of the
issues and concerns about the risk assessment of formaldehyde
revolved around a complicated mix of risk assessment policy
judgments and scientific judgments. On both s ides of the debate,
there was often no clear distinction drawn between scientific and
policy judgments O At the time the risk assessment was prepared,
there were no uniform federal guidelines for carcinogenic risk
assessment irt use. Such guidelines may'~ave been helpful in
providing a scientif ic and policy framework to support the CPSC
risk assessment, and in drawing sharper distinctions between
scientific and policy judgments employed in risk assessments.
Critics' comments may have focused on the generic scientific and
policy issues raised in the guidelines. Furthermore, adherence to
guidelines may have fostered a greater degree of explicitness in
the use of inference options applied, and reduced the degree of
inconsistency in interpretations among the agencies ~ i O e. ~ CPSC
and EPA).
The CPSC risk assessment may have !'enefitted from peer review
by art independent science advisory panel. In general g this is
good practice for all federal risk assessments.
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31
E. PERFORMANCE CONSIDERATIONS
1. Ab ility to obtain scientific information.
CPSC staff felt that there was a problem obtaining pertinent data
from CIIT as it was needed. Time-to-`c~or data and information on
benign tumors was withheld until the release of the full final
CTIT report in February 1982 (three months after the completion of
the final CP5C formaldehyde risk assessments. Consequently,
time-to-~or and benign tumor data were not cons idered in the
final risk assessment in any quantitative fashion. Both pieces of
information would have increased the risk had they been factored
into the risk assessment.
Other da ta, which could have weighted the evidence toward a
reduced risk, was also withheld by CRT, although the results of
these studies -were presented in part in November 1980 at a CIIT
conference. One study dealt with evidence suggesting that fo.~al-
debyde was not genotoxic. Another report was an epidemiology
study which yielded negative results. In the view of CPSC,
detai led documentation ~ f these resuL ts have, as ye c, not been
released.
One of the most important pi eces of scientific information is
the pathology s [ides from the initial CIIT study. Six patholo-
gist~ representing IRI`G there permitted to review the s rides in the
middle of the study (January 1980~. No further review has been
permitted since then, although CPSC and the IRLG Formaldehyde Task
Group had requested such a reviews.
CIIT maintains the position that, as a matter of policy, they
lo no~c release data to any one party alone (i.e., the government);
that the release of data has to be made public, and is nor privy
to any one interes t group.
2. credibility of assessments, likelihood that interested parties
would accept them as definitive.
Hazard Ident if ic at ion
The Formaldehyde Panel, IARC, NIOSH, the Sel ikof ~ and Hammond
Committee Report to the American Cancer Society, the heads of NCI,
NIEHS, and NCTR and three distinguished scientists at New York
University Medical Center have all concurred that formaldehyde is
a definite animal c arc inogen and should be cons idered to pose a
human carcinogenic risk. Some interested parties could dispute
these assertions, but it is likely that most would not.
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32
Quantification and Characterization of Risk to Humans
Representatives of CIIT and the formal'1ebyde industry were
highly critical of CPSC'~ quantitative risk assessment. As
detailed in Question C.11, two main points of criticism focus on
the choice ~ f the dose-response curve, and the quality of CPSC ' s
exposure da t a .
What was the extent of diversity of policy orientations
. .. .
represented within the assessment croup i tself . What was the
decree to which interes t pressures would be exerted from
outside the assessment group? What {:~5 the ·~s~onsivenes s of
the assessment to these diverse interests7
_
Both the hazard identification and the quantification of risk to
huffs were performed solely by federal scientists. Hence, the
extent of diversity of policy orientations was quite limited. It
does not appear that there was any degree of integer t pressure
exerted from outs ide the group.
4 What were the time ant resources necessary to comr~le to the
.
. .
risk assessment?
Hazard Identification Assessment
The federal panel consisted o f 16 scientists working part-time
actual percentage unknown) for 9 months .
Characterization of Risk to Humans
Seven CPSC staff persons worked full or part-time over two years
collecting and reviewing data and reviewing comments.
Me cancer risk assessment document (excluding the effort
needed to obtain exposure data) required one person working full
time for one year.
5. Responsiveness of assessment agenda to public concerns
. . .
interest group concerns, professional codeine, an~ e~er~euce
of new scientific data.
It appears that CPSC responded to public concerns regarding
irritation and sensitivity effects with cautious but deliberate
action, and it respond to the newly emerging information on
formaldehyde as a Potts tial human carcinogen with swift, decisive
action.
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33
As described in detail in Question A.2, the first public
concerns voiced in October 1976 regarded irritation effects from
formaldehyde release in UFFT residences. Wer the next couple of
years, several thousand similar complaints were filed with CPSC.
In order to obtain more detailed information on the full extent of
human heal th concerns, CPSC asked the National Academy of
Sciences, in May 1979, to prepare a comprehensive report. The
report -~as completed in March 1980. Public hearings were 'nerd
from December 1979 through February 1980 as industry, state and
local government officials, scientists, and others testified on
the question of UFFI ant formaldehyde release. As a result of all
this activity, on June 10, 1980, CPSC issued ~ proposed rule '.~ch
would require UFFI manufacturers to label their products giving
specified performance and technical information to prospective
purchasers. This rule was never made effective because in the
view of CPSC the new emerging cancer data required more stringent
rutemaking.
lathe first preliminary data from the CIIT rat studies was
presented to CPSC in October 1979. One month later, a briefing
package prepared by s gaff was sent to the commits loners . In
January 198~), an IRLG task force visited CIIT to verify the
findings. In April 1980, the CPSC-requested Formal`lebyde Panel
was formed to assess all current literature and make reco~enda-
tions as to the severity of health ef facts. T'ne final report in
November 1980 concluded that formaldehyde was a potential human
carcinogen. In February 1981, CPSC published a proposed rule to
ban UFFI. In October 1981, the final CPSC cancer risk assessment
was completed. TO April 1982, CPSC published a final rule to ban
IJFF1 .
6. Ability of the risk assessment to identify research needs.
Interest in the possible harmful effects of formaldehyde generated
an abundant 1 is tiny of research needs . The CPSC-sponsored
National Academy of Sciences study on health effects o f Cormal-
dehyde (March 1980 ~ identified twelve research needs including the
areas of carcinogenicity, reproduction and teratogenic effects,
sensitivity of population subgroups, pharmacokinetic studies,
sources and fates of formaldehyde, and percutaneous penetration.
The Formaldehyde Panel report identified research needs in
teratology, animal reproduction, human reproduction, mutagenicity,
carcinogenicity (pharmacokinetics, other routes of administration,
neoplastic transformation of mammalian cells), epidemiologic
research, and the ability of formaldehyde to interac t with other
pal lutants .
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Representative terms from entire chapter:
inference options
3/+
A major research effort has already begun with the goal of
obtaining more definitive results from epidemiological data. Both
NCI and NIOSH are examining data on large numbers of workers with
a history of high formaldehyde exposure. '
3S
10. Mode and frequency of communication between assessors and
regulators .
Hazard Identification
lye Formaldehyde Panel, in its appraisal of formaldehyde as a
potential l`uman carcinogen, appeared to be acting entirely
independent ty o f agency regulators .
Characterize ion of Rick
CPSC appears to 'nave organizational separation between the
assessors and the regulators. lathe assessors, consisting of staff
from the Directorate of Health Sciences, performed their function
wi thou t apparent contac t wi th or guidance by the program team and
the commissioners, who are the regulators.
36
SOME: IMPORTANT REFERENCES CITEI)
IN FORMALDEHYDE CASE STUDY
Crump, K. S . and W. W. Watson. 1979. Global 1979. ~ fortran
program to extrapolate dichotomous animal carcinogeraicity data to
low doses. Dept. of Mathematics and Statistics, Louisiana Tech
Univers ity.
EPA (Environmen~at Protection Agency). 1976. Health risk and economic
impact assessments of suspected carcinogens. Fed. Reg. 41: 21402.
EPA ~ Environmental Protect ion Agency) . Of fice of Research and
Developments Carcinogen Assessment Group. August 8, 1980. The
Carcinogen Assessment Group's method for determining the unit risk
estimate for air pollutants. External review copy prepared for
Office of Air Quality Planning and Standards and Office of Air,
Noise and Radiation.
F})A (Food and Drug Administration). 1979. Chemical compounds in
Eood~producing animals 9 criteria and procedures for evaluating
assays for carcinogenic residues. Fed. R=go 44 17070.
Food Safety Council, Final Report of Board of Trustees. June 1989 0
~ Proposed Food Safety Evaluation Process.
Gibson 9 J o E a December 15, 1981. Le t te r from Chemical Industry
Ins t i tute ~ f Toxico logy (CIIT ~ to Consumer Produc ~ .Sa fe ty
Commiss ion ~ CPSC ~ .
Gibson, J. E. February 1;, 19820 Letter from Chemical Industry
Ins t itute o f Toxico logy ~ C IIT ~ to Nancy S teort s, Cha irman, Cons ume r
Product Safety ·^ommiss ion (CPSC ~ .
IARC (International Agency for Research on Cancer) 9 the Working
Group O May 1982. Monograph on the Evaluation of the Carcinogenic
Risk of Chemicals to Humans. Some Industrial Chemicals and Dye
Stuffs: Formaldehyde, pp. 345-3890
TRLG (Interagency Regulatory Liaison Group), Work Group on Risk
Assessment. 19790 Scientific bases for identification of
potential carcinogens and estimation of risks. Fed a Reg 0 44:39858.
Mantel, N. and M. A. Schneide~=an. 19750 Estimating "Safe" levels,
a hazardous undertaking. Cancer Res. 35: 1379-138f'.
NAS (National Academy of Sciences). March 1980. Formaldehyde:
An Assessment of Its Realth Effects.
37
NIOSH (National Institute for Occupational Safety and Health).
Current Intelligence Bulleting #34. April 15, 1981.
Formaldehyde: Evidence of Carcinogenicity .
NYU (New York University). R. E. Albert, A. R. Sellak~ar,
S. Laskin, M. Ruschner, N. Nelson and C. A. Snyder. 1982. Gaseous
formaldehyde and hydrogen chloride induction of nasal c ancer in the
rat. J. National Cane. Inst. 68 :597-602.
OSIP (Office of Sc fence and Technology Po ticy) . D. R. Calkins,
R a L a Dixon, c: . R. Gerber, 1) . Zarin, and G. S . Omenn. 1980 .
Indentification, characterization, and control of potential human
carcinogens: A framework for federal decis ionmaking. J . National
Cane. Inst. 64 :169-176.
Report of the Federal Panel on Formaldehyde. November 1980.
Submitted to S. B. ICing, Chairman, U. S. Consumer Product Safety
Commission. Also published February 1982, Environmental 'Realth
Perspectives. 43: 139-168.
Selikof f, I . ~ . and E. C. Hammond. February 25, 1981. Carcino-
genicity of formaldehyde: final report to the American Cancer
Society by the Environmental Cancer Info~!uat ion Unit .
Environmental Sciences Laboratory, Mount Sinai School or Medicine.
Todbunter, J. A. February 10, 1982. Review of data available to the
administrator concerning formaldehyde and di(2-ethythexyl~phtha-
late (~EHP). Memorandum to Anne Gorsuch, Administrator,
En~rironmenta 1 Pro tee ~ ion Agency .
