Ni Hms 636912

A RECOMMENDED OCCUPATIONAL EXPOSURE LIMIT
FOR FORMALDEHYDE BASED ON IRRITATION

Dennis Paustenbach
McLaren/Hart, Environmental Engineering, ChemRisk Division,
Alameda, California, USA
Yves Alarie
Graduate School of Public Health, University of Pittsburgh,
Pittsburgh, Pennsylvania, USA
Tom Kulle
Environmental Health Sciences, Edgewood, Maryland, USA
Neil Schachter
Mount Sinai Medical Center, New York, New York, USA
Ralph Smith
Department of Industrial Hygiene, School of Public Health,
University of Michigan, Ann Arbor, Michigan, USA
James Swenberg
Department of Veterinary Medicine and Toxicology, University
of North Carolina, Chapel Hill, North Carolina, USA
Hanspeter Witschi
Department of Toxicology, Institute of Toxicology and
Environmental Health and Department of Molecular Biosciences,
School of Veterinary Medicine, University of California at Davis,
Davis, California, USA
Susan B. Horowitz
ChemRisk, Alameda, California, USA
In recent years, several regulatory agencies and professional societies have recommended
an occupational exposure limit ( OEL) for formaldehyde. This article presents the findings of
a panel of experts, the Industrial Health Foundation panel, who were charged to identify
an OEL that would prevent irritation. To accomplish this task, they critiqued approximately
150 scientific articles. Unlike many other chemicals, a large amount of data is available
upon which to base a concentration-response relationship for human irritation. A mathe-
Received 1 May 1995; sent for revision 19 June 1995; accepted 10 April 1996.
Susan B. Horowitz was not a member of the panel but assisted in panel deliberations and
in preparing this article.
Address correspondence to Dennis Paustenbach, McLaren /Hart/ChemRisk, 1135 Atlantic
Avenue, Alameda, CA 94501, USA.
217
Journal of Toxicology and Environmental Health, 50:217–263, 1997

Copyright © 1997 Taylor & Francis
0098-4108/97 $12.00 + .00
218 D. PAUSTENBACH ET AL.
matical model developed by Kane et al. ( 1979) for predicting safe levels of exposure to
irritants based on animal data was also evaluated. The panel concluded that for most per-
sons, eye irritation clearly due to formaldehyde does not occur until at least 1.0 ppm.
Information from controlled studies involving volunteers indicated that moderate to severe
eye, nose, and throat irritation does not occur for most persons until airborne concentra-
tions exceed 2.0–3.0 ppm. The data indicated that below 1.0 ppm, if irritation occurs in
some persons, the effects rapidly subside due to “accommodation.” Based on the weight
of evidence from published studies, the panel found that persons exposed to 0.3 ppm for
4–6 h in chamber studies generally reported eye irritation at a rate no different than that
observed when persons were exposed to clean air. It was noted that at a concentration of
0.5 ppm ( 8-h TWA) eye irritation was not observed in the majority of workers ( about
80% ) . Consequently, the panel recommended an OEL of 0.3 ppm as an 8-h time-weighted
average (TWA) with a ceiling value ( CV) of 1.0 ppm ( a concentration not to be exceeded)
to avoid irritation. The panel believes that the ACGIH TLV of 0.3 ppm as a ceiling value
was unnecessarily restrictive and that this value may have been based on the TLV
Committee’s interpretation of the significance of studies involving self-reported responses at
concentrations less than 0.5 ppm. The panel concluded that any occupational or environ-
mental guideline for formaldehyde should be based primarily on controlled studies in
humans, since nearly all other studies are compromised by the presence of other contami-
nants. The panel also concluded that if concentrations of formaldehyde are kept below
0.1 ppm in the indoor environment ( where exposures might occur 24 h/ d) this should pre-
vent irritation in virtually all persons. The panel could not identify a group of persons who
were hypersensitive, nor was there evidence that anyone could be sensitized ( develop an
allergy) following inhalation exposure to formaldehyde. The panel concluded that there
was sufficient evidence to show that persons with asthma respond no differently than
healthy individuals following exposure to concentrations up to 3.0 ppm. Although cancer
risk was not a topic that received exhaustive evaluation, the panel agreed with other sci-
entific groups who have concluded that the cancer risk of formaldehyde is negligible at
airborne concentrations that do not produce chronic irritation.
Over the past 40 yr, many organizations in numerous countries

have proposed occupational exposure limits (OEL) for airborne contam-
inants (Cook, 1986; Paustenbach, 1994). The limits or guidelines that
have gradually become the most widely accepted both in the United
States and abroad are the threshold limit values (TLVs) issued annually
by the American Conference of Governmental Industrial Hygienists
(ACGIH). The TLVs are limits that refer to airborne concentrations of
substances and represent conditions under which it is believed that
nearly all workers may be repeatedly exposed day after day without
adverse effect (ACGIH, 1972, 1982, 1995). The ACGIH recognized
long ago that because of the wide range in individual susceptibility, a
small percentage of workers may experience discomfort from some
substances at concentrations at or below the TLV, and that a smaller
percentage may be affected more seriously by aggravation of a preex-
isting condition or by development of an occupational illness (Cooper,
1973; Zielhuis, 1974; ACGIH, 1982; Stokinger, 1981; Omenn, 1982;
ACGIH, 1995). This limitation, although perhaps less than ideal, has
been considered a practical one since attempts to control workplace
contaminants so low as to protect unusually susceptible individuals are
OCCUPATIONAL EXPOSURE LIMIT FOR FORMALDEHYDE 219
often impossible to achieve because of either engineering or economic

limitations. It should be noted that the TLV Committee does not con-
sider economics, analytical limitations, or technical feasibility when set-
ting its values.
Between 1988 and 1991, the ACGIH TLV Committee evaluated
formaldehyde, one of the most industrially significant chemicals used
in the United States. In 1989, it proposed a TLV of 0.3 ppm as a
ceiling value to replace the 1.0 ppm (8-h TWA) figure that had been
in place for the prior 6 yr. In 1992, the ACGIH adopted a TLV-CV
of 0.3 ppm. They also classified it as an A2 suspected human car-
cinogen. The TLV Committee stated that its recommendation was
based on evidence of irritation in humans occupationally exposed to
formaldehyde, as well as new knowledge about responses reported in
other settings such as mobile homes (ACGIH, 1991). Based on infor-
mation contained in the documentation of the TLV (1991), it was clear
the TLV Committee believed that the cancer hazard was insignificant if
irritation was prevented. The recommendation of the TLV Committee
was considered unnecessarily stringent by many firms that produced
and/or used formaldehyde, as well as their toxicology and medical
staffs. In the view of a number of professors who had studied
formaldehyde and industry scientists, the TLV Committee had misinter-
preted some of the published literature. As a result, the Formaldehyde
Institute asked the Industrial Health Foundation (IHF) to convene a
panel of experts to independently identify an OEL that would prevent
irritation.
The IHF panel was charged to evaluate the rationale for the
ACGIH TLV and the information upon which the TLV was based.
Consistent with the intent of the TLV Committee, the objective of the
panel was to identify an airborne concentration of formaldehyde at
which “it is believed that nearly all workers may be repeatedly
exposed day after day without adverse health effects” (ACGIH, 1995).
Sensory irritation, for purposes of this evaluation, was defined as a
subjective response to annoying odor or the sensation of burning eyes,
nose, and throat. This article describes the process used by the panel
to identify an OEL for formaldehyde. The methods used to interpret
published data, and especially case reports, should be applicable to
setting OELs for other irritants.
EXPOSURE TO FORMALDEHYDE
Formaldehyde is typically sold as an aqueous solution (formalin),
or as paraformaldehyde, a white amorphous powder or flake [NIOSH,
1976; California Air Resources Board (CARB), 1991]. Its major use in
industry is in the polymerization of phenolic, urea, and melamine
resins. These resins are used to manufacture plywood, medium-density
fiberboard, and particle board (NIOSH, 1976; Gibson, 1983). Other

uses of formaldehyde include the production of fertilizers, dyes, disin-
fectants and germicides, hair shampoo and conditioner preservatives,
embalming fluids, hardening agents, oil-well corrosion inhibitors, and
permanent-press treatment for textile fabrics.
Formaldehyde in the ambient air has been measured in cities
throughout North America where heavy traffic and industry create
excessive amounts of photochemical smog and hence, formaldehyde.
The National Research Council (NRC, 1980, 1981) has reported that
formaldehyde concentrations in ambient air varies from less than 10
ppb to as high as 90–150 ppb in areas of heavy traffic or smog. The
major indoor sources of formaldehyde are off-gassing of urea-formalde-
hyde foam insulation, particle board, plywood, fabrics, and, to a lesser
extent, cigarettes and indoor combustion sources (Gibson, 1983). It is
estimated that the mean indoor concentration of formaldehyde in con-
ventional homes in the United States is about 0.03–0.050 ppm
(WHO, 1989), with values in the range of 0.02 to 0.150 ppm (CARB,
1991). Typical indoor formaldehyde concentrations in buildings contain-
ing urea-formaldehyde structural components range between 0.05 and
0.6 ppm (NRC, 1981; Harris et al., 1981; Breysse, 1981; CARB,
1991). In the 1980s, it was not uncommon to measure formaldehyde
in new mobile homes at concentrations that ranged from 0.10 to 0.80
ppm (NRC, 1981; WHO, 1989). The estimated mean indoor formalde-
hyde concentration in conventional homes in the United States is
about 0.03 ppm (WHO, 1989).
Cigarette smoke contains 10–15 mg formaldehyde per cigarette,
and persons who smoke 1 pack of cigarettes per day can inhale as
much as 0.38 mg formaldehyde (NRC, 1980). Concentrations of
formaldehyde in passive or second-hand smoke have been estimated to
be approximately 0.23–0.27 ppm (Gammage & Gupta, 1984).
Occupational exposures usually result from the fugitive emissions of
formaldehyde vapor, off-gassing during product manufacturing, or during
use of formaldehyde-containing products. The principal hazard associated
with workplace exposure is irritation of the eyes, skin, and respiratory
tract (NIOSH, 1976; OSHA, 1985; Hunter, 1987; ACGIH, 1995).
TLVs for Formaldehyde (1945–1990)
The first list of recommended occupational exposure limits (OEL),
identified as maximum allowable concentrations (MACs), was published
in 1942 by a Subcommittee on Threshold Limits of the National
Conference of Governmental Industrial Hygienists, the American Stand-
ards Association (ASA), and other professional groups (ASA, 1944;
Cook, 1945, 1986). The objective of this group was to develop quan-
titative limits to protect workers from the adverse effects of workplace
air contaminants and physical agents. To their credit, their approach to
developing OELs has generally been shown to be acceptable even by

today’s standards (Cook, 1945; Smythe, 1956; Stokinger, 1970; WHO,
1977; LaNier, 1984; Cook, 1986; Doull, 1991). Table 1 presents the
worldwide OELs for formaldehyde.
The ACGIH TLVs for formaldehyde have changed on a regular
basis over the years (Table 2). In 1944, the American Standards
Association (ASA) set a maximum allowable concentration (MAC) of
10 ppm for formaldehyde based on the observations of skin and
mucous membrane irritation (ASA, 1944). In the United States, the
term MAC was the predecessor to the acronym TLV.
In 1948, a TLV-TWA (time-weighted average) of 5 ppm was adopted
for formaldehyde based on the observation of eye, respiratory tract
and skin irritation (ACGIH, 1948). In 1963, the 5 ppm TLV-TWA was
TABLE 1. Worldwide occupational exposure limits (OEL) for formaldehyde in 1994
Country/agency OEL (ppm) Type of guideline
NIOSH 0.1 C (15 min)

World Health Organization (WHO) 0.24 TWA
ACGIH (1991) 0.3 C
Denmark 0.3 C
Germany 0.4 STEL
USSR (former) 0.4 TWA
Germany 0.5 TWA
U.S. Occupational Safety and Health Administration 0.75 TWA
(OSHA, 1992)
Hungary, Yugoslavia 0.8 TWA
Finland, Norway, Sweden 1.0 C
ACGIH (1990), AIHA, Australia, Austria, Germany, 1.0 TWA
Italy, the Netherlands, Switzerland/OSHA
Brazil, Chile 1.6 TWA
Bulgaria 0.8 STEL
Australia, Belgium, India, Japan, the Netherlands, 2.0 C
Venezuela
ACGIH (1990), AIHA, Argentina, France, 2.0 STEL
the Netherlands, OSHA, United Kingdom
Hungary 1.6 STEL
Czech Republic, Poland 1.6 TWA
Argentina, Mexico, United Kingdom 2.0 TWA
People’s Republic of China 2.5 TWA
Australia 3.0 STEL
Rumania 3.2 C
Czech Republic 4.1 C
Indonesia 5.0 C
Egypt, Republic of China 5.0 TWA
Note. All limits were obtained from one of the following publications: WHO (1977), Cook
(1986), AIHA (1990), ACGIH (1989, 1992). C, ceiling value (maximum instantaneous concentra-
tion). STEL, short-term exposure limit (15 min; up to 4 times per day). TWA, time-weighted
average (8 h/d).
TABLE 2. Changes in the ACGIH TLV for formaldehyde and the rationale (1946–1992)
Concentration
Year (ppm) Guideline Rationale
1946–1947 10 MAC-TWA Prevent skin and mucous membrane irritation

1948–1962 5 TLVa-TWA Protective of respiratory injury
1963–1971 5 TLV-Ceiling Protective of respiratory injury
1972–1984 2 TLV-Ceiling Protective of eye irritation, mucous membrane
irritation, disturbed sleep
1985 1 TLV-TWA Prevent eye and nose irritation
1985 2 TLV-STEL Minimize cancer hazard
1992 0.3 Ceiling Eliminate eye and upper respiratory tract
irritation; de minimis cancer risk
Note. MAC, maximum allowable concentration; TWA, time-weighted average; STEL, short-term
exposure limit; Ceiling, maximum instantaneous concentration.
a
MACS become TLVs during this time period.
revised and a 5 ppm ceiling value (CV) was adopted based on eye
and respiratory tract irritation reported at 5–6 ppm (Elkins, 1950;
ACGIH, 1962) and possible skin sensitization (Smythe, 1956).
Due to reports of complaints of irritation at concentrations well
below 5 ppm, such as annoying odor, sensory irritation, and disturbed
sleep, the TLV was reduced to a ceiling value of 2 ppm in 1972
(ACGIH, 1972). This value was considered “adequate to prevent seri-
ous or persistent adverse effects” (ACGIH, 1980).
In 1985, the TLV Committee adopted a TLV-TWA of 1 ppm with a
15-min short-term exposure limit (STEL) of 2 ppm and designated it as
an “A2 carcinogen,” that is, an industrial substance suspected of car-
cinogenic potential for humans (ACGIH, 1986). In the opinion of the
TLV Committee, which met in 1985, the TLV-TWA of 1 ppm “. . . is
adequate and no serious or persistent adverse effect should develop.
This value may not be low enough to prevent the hypersusceptible
person from either suffering irritation or complaints.” The committee
noted that “irritation of the eyes and nose occurs down to 1.0 ppm
and it is suggested that symptoms also occur below 1.0 ppm as well”
(ACGIH, 1986). The A2 carcinogen classification was assigned to
formaldehyde based upon an inhalation study i n which rats were
exposed to concentrations of 2.0, 5.6, or 14.3 ppm for 24 mo. An
increased incidence of squamous-cell carcinomas in rats was reported
at the airborne concentrations of 14.3 ppm. At 2.0 and 5.6 ppm, no
increase in nasal tumors was observed (Kerns et al., 1983).
In 1989, the ACGIH proposed lowering the TLV based on the
observation of eye and upper respiratory tract irritation in humans (a)
in controlled inhalation studies, (b) in the workplace, and (c) in mobile
homes. A TLV of 0.3 ppm as a ceiling limit (CV) was proposed based
upon the opinion that this concentration should further reduce sensory
irritation for workers handling formaldehyde or formaldehyde-containing
products. Moreover, in view of the reported concentration-dependent
carcinogenic effect in the rat and mouse and the inadequate epidemio-
logic data on the cancer risk in humans, the TLV Committee concluded
that “it is advisable to reduce formaldehyde workplace exposure to the
lowest possible level” (ACGIH, 1989). In 1991, the ACGIH extended
the comment period for formaldehyde on the Notice of Intended
Change (NIC) from 2 to 3 yr. In May 1992 the ACGIH adopted the
0.3 ppm TLV-CV and the rationale was published in the documenta-
tion (ACGIH, 1991).
IHF Panel’s Approach to Assessing the Literature
The IHF panel reviewed about 150 published papers to assess the
irritant properties of formaldehyde and recommend an OEL to protect
workers from such effects. These were divided into four categories: ani-
mal studies, controlled human studies, worker surveys, and community/
residential surveys. The community surveys involved studies of residents
of mobile homes or dwellings that contained urea-formaldehyde foam
insulation and/or other sources of formaldehyde. Papers dealing solely
with environmental measurements, cancer, or allergic contact dermatitis,
but without reference to sensory or respiratory-tract irritation, were not
evaluated. Virtually all of the papers upon which the TLV Committee
based its 1991 recommendation were evaluated.
During meetings of the panel, each paper was critically evaluated.
Any differences in interpretation were resolved and a consensus posi-
tion for each paper was developed. All of the papers reviewed by the
panel are presented in the references. Papers cited but not discussed
indicate that the paper either did not provide sufficient information on
which to draw conclusions or that it was not pertinent to the task of
setting an OEL.
ANIMAL TOXICOLOGY
Twenty-four animal studies dealing with irritation (sensory irritation
or inflammatory reaction) were reviewed by the panel, and 11 are
discussed here. These studies were evaluated to identify the types of
toxicological effects that can be expected to occur in humans, as well
as to obtain an understanding of the role played by concentration (C)
versus time (C × T) of exposure (important when setting TLVs for
systemic toxicants). Due to the very high concentrations to which
animals were exposed in most studies, they were not very helpful to
setting an 8-h OEL for humans.
Acute Studies (Animals)

Formaldehyde has frequently been evaluated in animal studies to
determine its potential acute and chronic effects (NIOSH, 1976; NRC,
1981). Sensory irritation by formaldehyde has been well documented
with respect to acute inhalation exposure, and the degree of irritation
has generally been found to be concentration, rather than concentration
times time (C × T), dependent (within certain concentration limits). An
inhalation LC50 of 664 ppm formaldehyde has been reported for cats
exposed for 8-h, and several different LC50s have been reported for
mice exposed for 2 h (NIOSH, 1976). An LC50 of 81 ppm has been
reported for rats, although the exposure duration and frequency were
not provided (Ivanoff, 1911). Following 10 h of exposure, mice and
rabbits exposed to 5–15 ppm showed clear signs of irritation (Salem
& Cullinbine, 1960). Irritation of the eyes, nose, throat, and lungs, as
well as cellular changes in the upper respiratory tract, have been
observed in animals exposed to concentrations greater than 2.0 ppm
(NRC, 1981; Hunter, 1987).
Kane and Alarie (1977) exposed Swiss Webster mice to concentra-
tions of formaldehyde ranging from 0.52 to 11.2 ppm for 10 or 180
min to evaluate sensory irritation following single and repeated expo-
sures. Ten-minute exposures to 3.0 ± 0.28 ppm resulted in a 50%
decrease in respiratory rate in mice. Repeated exposures on consecutive
days produced an increase in the response when the concentration was
above 0.3 ppm. The authors suggested that based on their data and
the model that they developed, the TLV should be set between 0.03
and 0.3 ppm to prevent eye, nose, and throat irritation in humans.
In 1979, Kane, Barrow, and Alarie presented additional data that
supported their model. They successfully predicted a relationship
between historical TLVs set to prevent sensory irritation based on the
decrease in respiratory rate observed in mice. The authors predicted that
a reasonable TLV for workers exposed to formaldehyde would be 0.3
ppm or less. This model has been evaluated and used many times over
the past 10 yr, and it has been shown to be a relatively accurate pre-
dictor of acceptable concentrations of human exposure to airborne
chemical irritants (Nielsen & Alarie, 1982; Nielsen, 1991; Schaper, 1993)
and is useful when good-quality human data are not available.
Chang et al. (1981) conducted a study involving mice and rats
that characterized differences in sensory irritation to formaldehyde and
to determine how the reflex apnea defense mechanism was maintained
during 10-min, head-only exposures. Comparisons were made between
nonexposed and pretreated animals. The pretreated animals were
exposed to 2, 6, or 15 ppm for 6 h/d for 4 d. Decreases in the res-
piratory rate and depression in minute volume were observed in a
concentration-dependent manner. At 15 ppm, 75% of the pretreated
mice had decreased minute volumes, whereas decreased minute vol-
umes were observed in only 33% of the mice not preexposed. The
authors concluded that formaldehyde exposure depressed the minute
volume in both mice and rats at 2, 6, and 15 ppm. In this study,
the rats were unable to minimize inhalation of formaldehyde, com-
pared to the mice. The panel concluded that due to the differences
in the ability of these two species to reduce their intake, mice and
rats may receive different absorbed doses (on a milligram per kilogram
basis) even though they are exposed to the same airborne concentra-
tion. Whether this fully explains why other species respond differently
is unknown. In a follow-up study, Chang et al. (1983) exposed rats
and mice to 15 ppm formaldehyde for 6 h and found a reduction in
minute volumes of 20% in rats and 50% in mice. Due to the reflex
apnea defense mechanisms measured in exposed mice, they likely
receive d a lower delivered dose per body weight, which correlated
with decreased histopathology and cell proliferation.
Lee et al. (1984) demonstrated that guinea pigs exposed to 6 and
10 ppm for 6 and 8 h per day for 5 d did not elicit immediate
pulmonary hypersensitivity reactions, although formaldehyde proved to
be a skin sensitizer in that species. The panel concluded from this
study that formaldehyde can induce dermal sensitization in a dose-
related manner and is not a pulmonary sensitizer or, if it is, it is of
very low potency. This study was considered by the panel relevant to
setting an OEL.
Morgan et al. (1986) evaluated the nasal mucociliary apparatus of
rats exposed to airborne concentrations of 0.5, 2, 6, and 15 ppm and
found that direct impairment of nasal mucociliary function occurred at
15 ppm. This study provided evidence that impaired function occurs
before morphological changes occur. Cumulative effects at concentrations
around 6 ppm and greater were also observed. They identified 0.5 ppm
formaldehyde as the no-observable-effect level (NOEL) for mucociliastasis.
The panel concluded that this study demonstrates a direct impairment of
nasal mucociliary function in rats exposed to 6 and 15 ppm, and is
consistent with the frog palate studies (Morgan & Patterson, 1984). It
was considered important to setting an OEL, since impairment of func-
tion was seen before morphological changes occurred.
Subchronic Studies (Animals)
Dubreuil et al. (1976) identified no significant symptoms of eye and
upper respiratory tract irritation in approximately 10% of rats exposed
to formaldehyde at concentrations of 1.6 and 4.6, but those exposed
to 8.1 ppm for 6 h/d for up to 2 mo had measurable irritation. Slight
irritation was observed at 1.6 ppm and the magnitude and severity of
the response at other doses was concentration dependent. The panel
concluded that this study suggests that an 8-h TWA rather than a CV
is acceptable since irritation was infrequently observed below 4 ppm.
The panel considered these data useful for deciding whether a CV or

STEL would be necessary to protect workers. The TLV Committee noted
that minimal adverse effects were observed at 4.6 ppm and that clear
signs of nasal irritation were observed at 8.1 ppm.
Monticello et al. (1989) identified an increase in the rate of cell
proliferation in the respiratory tract of monkeys exposed to 6 ppm
formaldehyde, 6 h/d, 5 d/wk for 6 wk compared to controls. Lesions
were induced in 42% of the nasal passages at 6 ppm (5 d duration).
No effect on cell proliferation, histopathology, or DNA–protein cross-
links in the maxillary sinuses of the monkeys was observed. The
panel concluded that this information showed that the monkey was
more sensitive than the rat to the acute and subacute effects of
formaldehyde. It was noted that there was an absence of changes in
the maxillary sinuses in monkeys. However, this information was not
considered directly applicable to setting an OEL.
Chronic Studies (Animals)
Rusch et al. (1983) conducted a 26-wk inhalation study of mon-
keys, rats, and hamsters. The animals were continuously exposed to
formaldehyde at concentrations of 0.19, 0.98, and 2.95 ppm for 22
h/d, 7 d/wk. The results showed induction of nasal lesions only in
rats and monkeys exposed to 2.95 ppm. The incidence of squamous-
cell metaplasia was 62% at 2.95 ppm. No lower respiratory tract
effects were observed at 2.95 ppm, and nasal irritation did not occur
at or below 0.98 ppm. The data showed that irritant effects were
concentration (C) rather than concentration (C) times time (T) depen-
dent. Based on this and other studies of irritants, it has generally
been considered that Haber’s law (C × T = response) does not apply
to formaldehyde and is likely not relevant for most other irritants. This
study suggested that irritation may not occur following exposures of 1
ppm or less for 22 h/d in these animal species. These data were
considered particularly relevant for setting an exposure limit for long-
term indoor exposure to formaldehyde.
Holmstrom et al. (1989) examined histological changes in the nasal
mucosa of rats following long-term exposure to 12.4 ppm formalde-
hyde and 25 mg/m3 wood dust. One of 16 rats had nasal squamous-
cell carcinoma after 104 wk of exposure to 12.4 ppm. The authors
concluded that an additive deleterious effect on the nasal mucosa fol-
lowed combined exposure to formaldehyde and wood dust; however,
irritation to the upper and lower respiratory tracts from exposure to
wood dust and formaldehyde simultaneously was not enhanced. There
was no difference in the occurrence of metaplasia or dysplasia
between the groups. The panel found this study useful in recommend-
ing an OEL, since even when wood dust and formaldehyde were pre-
sent together, concentrations up to 3.0 ppm did not appear to pose a
significant cancer hazard.
HUMAN STUDIES
Seventy-four human studies were identified and 52 were considered

relevant to setting an OEL by the panel. Ten were considered particu-
larly useful.
Numerous studies have shown that exposure to formaldehyde vapor
at high concentrations will cause irritation of the eyes, nose, throat,
and respiratory tract of workers. In humans, discomfort will often
occur almost immediately following exposure to 4–5 ppm in air
(Conlon & Mason, 1984). Intense lacrimation and difficulty in breath-
ing may occur at 10–20 ppm along with severe irritation of the eyes,
nose, and throat (Zurlo, 1983). Over the past 10 years, numerous
investigations of the physiological effects of formaldehyde have been
conducted with healthy individuals, asthmatics, and industrial workers,
and these are the best data upon which to set an OEL.
The panel reviewed all of the available studies involving human
exposure to formaldehyde in order to identify the concentrations at
which workers rarely, if ever, experience irritation. The goal was to
construct a concentration-response curve for reported sensations of eye
and nose irritation for concentrations up to 3.0 ppm. The three types
of data reviewed by the panel included controlled human studies,
worker surveys, and community surveys. Review of the human expo-
sure studies clearly demonstrated that eye irritation occurred at con-
centrations lower than that which caused nose/throat irritation. Table 3
and Figure 1 present the concentration-response data for eye irritation.
Analytical Methods
Knowledge of the sensitivity and accuracy of the analytical methods
that were used to measure formaldehyde concentrations in air was
considered important to insure that the data from the various studies
were valid. Unfortunately, i t was difficult to determine if the sampling
and analytical methods were reliable because a thorough description
of the procedures was not always presented by t he various investiga-
tors. It was impossible, therefore, to state with certainty, e ven after
determining that good analytical methods were used, that the results
were reliable. Calibration curves and other supporting data factors
were almost never provided. Thus, the panel assumed that the investi-
gators were competent and that they correctly used the methods to
which they referred.
Studies performed on populations exposed in the workplace or in
the community may have had some degree of analytical interference.
Fortunately, most of the analytical procedures used, primarily those
relying on color development with chromotropic acid, are specific for
formaldehyde and are not plagued by interference problems in the
presence of reasonable concentrations of most other substances. Other
methods, in contrast, are not specific for formaldehyde, but in the
absence of interferences are quite satisfactory. In short, one has to

evaluate each study to understand whether the presence of interfering
substances could have affected the results either negatively or positively.
The most widely used methods for measuring formaldehyde con-
centrations in air are based on the formation of a colored complex
with an organic reagent known as chromotropic acid. This method
has been used for many years. The definitive paper regarding its use
in air pollution studies was published by Altshuller et al. (1961), and
it has been validated several times and modified by various investiga-
tors. When samples are properly collected and analyzed, the method
is specific for formaldehyde and yields results of acceptable accuracy
and sensitivity; the collection efficiency ca n vary significantly, however,
depending upon the specific absorbing system used. For example, if
distilled water is the collection fluid, then samples obtained using a
single midget impinger absorb only about 80% of the true concentra-
tion. The addition of a second impinger in series improves the collec-
tion efficiency to essentially 100%.
Controlled Human Studies
Seventeen studies involving human exposures were reviewed by
the Panel, thirteen of which are discussed here. Ten were considered
particularly useful to setting an OEL and/or in understanding whether
asthmatics are more susceptible to experiencing an asthmatic episode
or irritation than healthy individuals when exposed to similar concen-
trations of formaldehyde.
Andersen and Molhave (1983) conducted a study i n which 16
healthy subjects (5 smokers) were exposed to 0.24, 0.4, 0.81, and 1.6
ppm formaldehyde. The purpose of the study was to determine the
concentration at which eye irritation occurred. Nineteen percent of the
respondents reported eye irritation at 0.24 ppm (study h , Figure 1).
Discomfort increased during the first 2 h of exposure up to 0.81
ppm; then irritation stabilized for the remaining 3 h. A decrease in
discomfort was observed at 1.6 ppm, thus indicating acclimatization.
After 5 h of exposure, 38% of the subjects had no complaints at 1.6
ppm and 63% had no discomfort at 0.81 ppm. The formaldehyde
concentrations were measured by collection of 1-h samples, analyzed
by t he chromotropic acid method. The panel considered this paper
important in identifying an OEL since no irritation was detected below
0.24 ppm in more than 80% of the volunteers. This study illustrates
the relatively wide variation in individual susceptibility to irritation
from formaldehyde.
Bender et al. (1983) exposed 12 human volunteers who had his-
torically reported eye irritation when exposed to formaldehyde to
0.35–1.0 ppm for 6 min. The purpose of the study was to determine
the frequency of eye irritation at various concentrations. Eye irritation
FIGURE 1. Linear concentration-response curve based on the data presented in Table 3 regarding
eye irritation due to formaldehyde. Linear least-squares regression analysis of the data presented
in Table 3, omitting the data for mobile home studies (points i*, j*, k*, and p*). The regressi on
equation is: %response = 19.6 + (17.4 × concentration in ppm); n = 2 4 , r 2, = .45. The regres-
sion, that is, positive slope, is significant (p < .001) and the 95% confidence interval for the
regressio n lines are shown. The data points b, e, and f represent studies with zero response at
zero concentration. The fit of the line does not vary appreciably if one fits the line with only
the controlled human studies or all of the studies.
was observed in 39% of the volunteers at 0 ppm, 42% at 0.35 ppm,

54% at 0.56 ppm, 57% at 0.7 ppm, 60% at 0.9 ppm, and 74 at
1.0 ppm (studies g, l, o, and q, Figure 1). The response time follow-
ing exposure to formaldehyde versus the response time for clean air
was the measured parameter. Although there was an apparent dose-
response relationship, the authors reported no significant difference in
response to air versus formaldehyde at concentrations less than 1.0
ppm. The chromotropic acid method was used to measure formalde-
hyde concentrations . The panel concluded that these results were
applicable only for setting a STEL or CV due to the extremely short

duration of the test.
Day et al. (1984) exposed 18 subjects to 1 ppm for 90 min in
an environmental chamber, 9 o f whom previously complained of
adverse effects from urea-formaldehyde foam insulation (UFFI) off-
gassing in their homes. The purpose of the study was to assess the
effects on lower respiratory tract function due to formaldehyde and
UFFI off-gassing. Eighty-three percent of the people experienced eye
irritation at 1.0 ppm (study t , Figure 1). The NIOSH method was used
for continuous sampling and wa s checked periodically with GASTEC
colorimetric tubes. The results are acceptable, although colorimetric
tubes are of limited accuracy. The authors concluded that neither
formaldehyde nor UFFI off-gases act as lower airway allergens or
bronchospastic irritants at 1.0 ppm. This study is useful in presenting
evidence that eye irritation readily occurs at 1.0 ppm, although it did
not provide information of irritant effects below that concentration.
Exposure to 1.0 ppm had no effect on the lower respiratory tract, nor
did it change pulmonary function. The panel decided that this study
provided evidence that an OEL that kept exposures below 1.0 ppm
was likely to prevent lower respiratory tract irritation and eye irritation
in most persons.
Green et al. (1987) evaluated the acute response following 1 h of
exposure to formaldehyde at 3.0 ppm in an environmental chamber
where 21 healthy subjects were engaged in intermittent, heavy exer-
cise. Sixteen volunteers with asthma were also exposed while they
were engaged in intermittent, moderate exercise. The purpose of the
study was to determine if there was a difference in the irritant
response between healthy and asthmatic subjects. At a concentration
of 3.0 ppm, 82% of the volunteers reported detecting an odor and
experiencing general irritation. At 3.0 ppm, 32% responded with nose
and throat irritation and 19–27% responded with eye irritation (study
z, Figure 1). Formaldehyde concentrations were monitored continuously
with two TGM-555 air monitors, which rely upon a modified Schiff
procedure. Backup samples were based on NIOSH method 125 (chro-
motropic acid). The panel considered these data reliable. The authors
concluded that acute exposure to 3.0 ppm produced similar results in
normal and asthmatic subjects. A greater than 10% decrement in FEV1
was observed in 13% of the group. An acute 10% drop in FEV1 is
probably clinically significant although clearly not on the order of an
acute asthmatic episode.
The important aspect of this study is that irritant symptoms were
similar in both the healthy and asthmatic test groups and that concen-
trations as high as 3.0 ppm did not provoke an asthmatic episode.
This work was important to the panel because it showed that people
who are typically considered hypersensitive o r hyperreactive are no
more at risk of suffering from formaldehyde-related irritation or asthma

than healthy individuals. The TLV documentation (ACGIH, 1991) cites
this study as evidence that it “is less than certain” that some asthma
attacks are specifically due to formaldehyde sensitization or allergy.
The authors concluded that their work clearly indicates that asthmatics
are not at greater risk of suffering an asthmatic attack or other toxic
effects than healthy individuals following exposure to formaldehyde.
Kulle et al. (1987; Kulle, 1993) randomly exposed 19 healthy, non-
smoking subjects at rest to formaldehyde at concentrations of 0, 1.0,
and 2.0 ppm for 3-h intervals in an environmental chamber. Ten of
these volunteers were also exposed to 0.5 ppm while the other 9
were exposed to 3.0 ppm formaldehyde. The subjects served as their
own controls. All of the subjects were also exposed to 2.0 ppm
formaldehyde during intermittent moderate exercise. The purpose of
these studies was to determine the frequency of irritant effects at vari-
ous concentrations and to compare differences in the response at rest
and during exercise. The frequency of eye irritation was 5% at 0
ppm, 0% at 0.5 ppm, 26% at 1.0 ppm, 53% at 2.0 ppm, and
100% at 3.0 ppm (studies a, n, s, u, and @, Figure 1). For odor
perception, the frequency rates were 5% at 0 ppm, 40% at 0.5 ppm,
26% at 1.0 ppm, 58% at 2 ppm, and 78% at 3.0 ppm. The preva-
lence of nose and throat irritation was 16% at 0 ppm, 10% at 0.5
ppm, 5% at 1.0 ppm, 37% at 2.0 ppm, and 20% at 3.0 ppm. In
this study no substantial differences were seen between male and
female symptom responses (Kulle, 1993). Formaldehyde concentrations
were monitored continuously with two TGM-555 air monitors (CEA
Instruments), calibrated weekly, with monitor agreement within 1%.
Daily backup samples were based on NIOSH method 125 (chro-
motropic acid). Formaldehyde concentrations measured by the impinger
method correlated well with those measured by the two CEA monitors
(r = .990). The analytical methods and results used in these studies
were considered accurate.
Kulle et al. concluded that exercise did not enhance irritant effects
and no eye irritation was observed at 0.5 ppm. The panel found
these studies to be particularly significant for setting an OEL. Virtually
no irritant effects occurred below 0. 5 ppm. The authors also showed
that an appreciable number of the volunteers will report eye, nose,
and throat irritation even when exposed to clean air. This “placebo
response” was also observed in other studies where subjects were
exposed to clean air versus air contaminated with sulfur dioxide
(Andersen et al., 1974), as well as in the Sauder et al. (1986) study
on formaldehyde (discussed later).
Sauder et al. (1986) exposed 9 healthy, nonsmoking volunteers to 0
ppm and 3.0 ppm formaldehyde in an environmental chamber for
180 min. Air was scrubbed with activated carbon filters prior to
entering the chamber. The purpose of this study was to determine the
frequency of irritant effects at 0 ppm and 3 ppm. The analytical pro-
cedure employed two TGM-555 air monitors, using a modified Schiff
procedure and NIOSH method 125 (chromotropic acid), which are
considered reliable. When there was no formaldehyde in the cham-
ber, 0 % responded with eye irritation, 22% reported detection of odor,
and 22% responded with nose and throat irritation (study b , Figure 1).
At 3.0 ppm, 70% responded with eye irritation, 67% claimed to
detect an odor, and 78% responded with nose and throat irritation
(study # , Figure 1). The authors concluded that acute exposure to 3.0
ppm formaldehyde produced small, transient decreases in pulmonary
function and mild to moderate eye and upper respiratory tract irrita-
tion. No change in airway activity or pulmonary function was
observe d when measured 24 h after exposure. Because irritation to the
nose and throat was reported by 22% of the volunteers even in the
absence of formaldehyde, it is clear that these symptoms may often
be erroneously attributed to environmental factors (just as described
here). The panel also considered this paper significant for setting an
OEL since eye and upper respiratory tract irritation were reported, yet
there was no “carryover” of effects 24 h later.
In another study, Sauder et al. (1987) exposed 9 nonsmoking,
asthmatic volunteers to 0 ppm and 3.0 ppm formaldehyde in an
environmental chamber for 180 min. The purpose of this study was
to determine the frequency of irritation in asthmatics and to compare
these results with the response rate in nonasthmatics. At 0 ppm, 22%
responded with eye irritation and 33% responded with nose and
throat irritation (study c , Figure 1). At 3.0 ppm, 78% responded with
eye irritation and 78% responded with nose and throat irritation
(study + , Table 3, Figure 1). Three parts per million caused mild eye,
nose, and throat irritation in asthmatics but did not cause bron-
choconstriction or impaired pulmonary function. The concentrations
were measured with two TGM-555 air monitors using a modified
Schiff procedure and NIOSH method 125 (chromotropic acid). These
concentrations were considered reliable. In comparing these results
with their prior work, the authors concluded that there was no differ-
ence in irritant response between asthmatics and healthy individuals,
nor was there a difference between males and females (with the
exception of one female who reacted moderately to severely). The
panel concluded that these results showed that asthmatics are no
more sensitive to formaldehyde than healthy individuals. This was con-
sidered valuable information and supported the findings of Kulle et al.
(1987), Green et al. (1987), and Kulle (1993). This study further con-
firmed that eye irritation is frequently reported by subjects exposed to
clean air (an apparent artifact of being involved in such tests, and
because some segment of the population has chronic eye irritation).
TABLE 3. Concentration-response information for formaldehyde obtained from irritation studies

(primarily eye) in well-controlled laboratory settings involving human volunteers
Study Response Concentration Duration

notationa (%)e (ppm) (h) Reference
a 5c 0 3 Kulle (1993)
b 0c 0 3 Sauder et al. (1986)
b
c 22 0 3 Sauder et al. (1987)
d 27b 0 0.66 Witek et al. (1987)
e 0c 0 0.66 Schachter et al. (1986)
d
f 0 0 0.66 Schachter et al. (1987)
g 39 0 0.1 Bender et al. (1983)
h 19c 0.24 5 Andersen and Molhave (1983)
i* 22 0.2 8–24 Ritchie and Lehnen (1987)
j* 90 >0.3 8–24 Ritchie and Lehnen (1987)
k* 24 0.4 8–24 Anderson et al. (1983)f
l 42 0.35 0.1 Bender et al. (1983)
m NA 0.3–0.5 NA Schuck et al. (1966)
n 0c 0.5 3 Kulle (1993)
o 54 0.56 0.1 Bender et al. (1983)
p* 56 0.8 24 Anderson et al. (1983)f
q 74 1.0 0.1 Bender et al. (1983)
r 24 0.7 (0.4–1.0) 8–24 Horvath et al. (1988)
s 26c 1.0 3 Kulle (1993)
t 83c 1.0 1.5 Day et al. (1984)
c
u 53 2.0 3 Kulle (1993)
v 47d 2.0 0.66 Schachter et al. (1987)
w 50c 2.0 0.66 Schachter et al. (1986)
c
x 33 2.1 0.025 Weber-Tschopp et al. (1977)
y 73b 2.0 0.66 Witek et al. (1987)
z 27b,c 3.0 1.0 Green et al. (1987)
c
@ 100 3.0 3 Kulle (1993)
# 70c 3.0 3 Sauder et al. (1986)
+ 78b 3.0 3 Sauder et al. (1987)
Note. *A mobile home study; NA, not available.

a
These notations correspond to the points in the concentration-response curve presented in
Figure 1.
b
Asthmatics.
c
Healthy volunteers.
d
Workers.
e
Response was defined as the percentage of the volunteers that reported either mild or moder-
ate eye irritations.
f
Evaluated for eye and nasal irritation collectively.
The panel considered these studies to be among the most important,

since all confounding factors were accounted for.
Schachter et al. (1986) exposed 15 healthy, nonsmoking volunteers
to 0 and 2.0 ppm formaldehyde for 40 min while at rest in an envi-
ronmental chamber. On separate days, they also exposed the groups
to 0 ppm and 2.0 ppm for 40 min with a 10-min period of moder-
ate exercise. The purpose of this study was to determine if exposure

to 0 ppm and 2 ppm caused changes in lung function during exer-
cise. At 2.0 ppm, 50% reported eye irritation, 30% reported nasal irri-
tation, 30% reported throat irritation, and 80% reported odor (study w,
Figure 1). At 0 ppm, 0% reported eye irritation, 27% reported nasal
irritation, 13% reported throat irritation, and 47% reported odor (study
e, Figure 1). A modified NIOSH method was used and validated by
means of a direct reading instrument, the Formaldemeter. The authors
determined that the analytical results agreed very closely and thus the
concentrations were considered accurate. The authors concluded that
short-term exposure to 2.0 ppm formaldehyde does not result in acute
changes in lung function in healthy individuals either at rest or during
exercise; for example, formaldehyde did not cause bronchoconstriction
in any of the subjects. The panel concluded that this investigation was
important to setting an OEL. Approximately 50% of the subjects expe-
rienced no irritant effects at 2.0 ppm. An interesting finding wa s that
none of the subjects reported eye irritation at 0 ppm, whereas nose
and throat irritation were reported. Based on this and other studies of
volunteers exposed in controlled chambers, the panel concluded that
at concentrations above about 0.3 ppm, eye irritation is perhaps a
more reliable response to formaldehyde in human studies than nose
and throat irritation. The panel concluded that when the incidence of
eye, nasal, and throat irritation is between 0 and about 20% (see
Figure 1 for eye irritation), it is usually not possible to attribute the
response to the treatment.
Schachter et al. (1987) exposed 15 laboratory workers to 0 ppm
and 2.0 ppm formaldehyde in an environmental chamber for 40 min.
On a separate day, the workers were exposed similarly during which
they performed 10 min of moderate exercise. The purpose of the
study was to evaluate the irritation hazard posed by short-term expo-
sures to formaldehyde. At 0 ppm, no eye irritation was reported,
although the frequency of odor detection was 47% and nasal and
throat irritation was 7% (study f , Figure 1). At 2.0 ppm, 47%
responded with eye irritation, 80% with odor detection, and 0%
responded with nose and throat irritation (study v, Figure 1). The
authors concluded that workers exposed to 2.0 ppm (under controlled
conditions) for periods up to 1 h do not develop adverse pulmonary
effects or other serious acute health effects. The concentrations reported
by the authors were considered accurate.
In comparing the results of their 1986 and 1987 studies, the
authors concluded that workers who have been chronically exposed to
formaldehyde respond similarly as non-preexposed healthy subjects. The
panel considered this observation a key finding. These data suggest
that repeated exposure may not enhance susceptibility to formaldehyde.
As noted by Schachter et al. (1986), a relatively high rate of nose and
throat irritation occurred at 0 ppm and, consistent with the results

observed of others, these rates are to be expected when querying per-
sons about subjective effects (Shusterman, 1992; Shusterman et al.,
1991; Holness et al., 1987, 1989). No eye irritation was reported at
0 ppm.
Schuck et al. (1966) evaluated eye irritation in volunteers who
were exposed to formaldehyde at 0.05–0.50 ppm. Five-minute exposure
intervals were used. The authors found that the incidence of irritation
was the same at 0.05 and 0.50 ppm. A concentration-response rela-
tionship was not observed until concentrations were above 0.3 ppm
formaldehyde. A linear relationship could be established between eye
irritation and formaldehyde concentrations ranging from 0.3 to 1.0
ppm, although the role of other contaminants cannot be determined
from the data. From this study it has been inferred that humans could
readily detect the presence of gas mixtures containing formaldehyde at
concentrations as low as 0.01 ppm. However, due to the manner by
which the formaldehyde was generated, peroxyacetyl nitrate (PAN),
nitrogen dioxide, and ethylene were possibly present in the chamber
(no analysis for them was conducted). The TLV Committee deemed
this paper significant since it demonstrated eye irritation at very low
concentrations, but it appears the committee may not have recognized
the likely presence and relative importance of other eye irritants.
Further, virtually all of the studies conducted since 1966 have yielded
data that are in conflict with these results. For this reason, the panel
gave little weight to this study.
Regrettably, the paper by Schuck et al. (1966) is cited in many
review papers as evidence that irritation occurs at concentrations as
low as 0.01 ppm, particularly in the NRC document (1980). It is often
used to justify OELs in the vicinity of 0.1–0.3 ppm. Interestingly, the
authors never stated that irritation was observed at 0.01 ppm but only
that the chromotropic acid method was “refined to allow measurements
in the 0.01 ppm range.” Because the authors noted that formaldehyde
was generated along with other pollutants by photo-oxidation of hydro-
carbons and that several irritants were present in the study mixture,
and because none of the 6 major, well-controlled, human studies that
were performed since 1966 report irritation at concentrations below 0.5
ppm, it was inferred by the panel that the sensory irritation reported
by the volunteers was not due to formaldehyde. For example, PAN
would be a much more potent irritant than formaldehyde, and if PAN
is present, this might explain the response reported.
Because the paper by Schuck et al. (1966) is cited so frequently
and because the panel does not believe that any irritant responses
reported below 0.3 ppm are due to formaldehyde, this paper deserves
additional discussion. First, there are no other data in the literature
that indicate that the eyes of humans can readily detect 0.01 ppm
formaldehyde (as was erroneously concluded by the authors from

their ow n data and as was repeatedly quoted in review articles).
Second, the authors themselves showed that the subjects could not
reliably detect eye irritation at less than 0.3–0.5 ppm under the
experimental conditions. Their own data suggest that the threshold for
sensory irritation in their experiments is in this range. In short, the
0.01 ppm figure quoted in many review articles as a concentration
that can produce eye irritation is a mistake and simply not supported
by the data presented by Schuck et al. It is also in conflict with the
results of all carefully controlled volunteer studies conducted over the
past twenty years.
Sheppard et al. (1984) exposed 7 nonsmoking asthmatic volunteers
to 1.0 and 3.0 ppm formaldehyde for 10 min during rest and exercise.
The purpose of this study was to determine whether these exposures
would cause bronchoconstriction in subjects with mild asthma. The
author concluded that acute exposures up to 3 ppm with and without
moderate exercise are unlikely to cause bronchoconstriction. A Wilkes
Miran 1A infrared spectrophotometer was used at a wavelength of 6.42
µm and corrected for water. The measurements of concentration should
be reliable. The results of this study are consistent with the results of
several previous investigations noted already. The panel considered this
paper to be significant in setting an OEL. This study provides good
evidence that up to 3.0 ppm, asthmatics are not at increased risk of
experiencing formaldehyde-induced asthma attacks. Further, there is no
evidence of any significant respiratory effects in asthmatics exposed up
to 3.0 ppm formaldehyde.
Weber-Tschopp et al. (1977) evaluated the eye blink rate of 33
healthy male subjects exposed to 0, 1.2, and 2.1 ppm formaldehyde
for 90-s durations. Eye blinking was considered to be an indicator of
eye irritation. The purpose of the study was to identify the threshold
concentration for eye irritation. At 2.1 ppm, 17% of the subjects had
excessive eye blinking, whereas 10% had moderately excessive eye
blinking and 7% had very excessive eye blinking. The eye blinking
rate doubled in 33% of the subjects at 2.1 ppm (study x , Figure 1).
At 0–1.2 ppm, no change in the normal eye blinking rate occurred,
and therefore this range of concentrations was considered a NOEL for
eye irritation. Concentrations were measured using the Technicon Air
Monitor IV system, which is based on the chromotropic acid method.
The measurements were considered reliable. The panel noted that the
exposure durations were too short to clearly indicate whether a CV,
STEL, or OEL-TWA was most appropriate. The authors stated that the
average irritation threshold for pure formaldehyde was in the range of
1–2 ppm. However, the panel concluded that the data indicate that
no effects were observed at concentrations below 1.2 ppm.
Witek et al. (1987) randomly exposed 15 asthmatic volunteers to 0
ppm and 2.0 ppm formaldehyde for 40 min (with and without 10
min of moderate exercise) in an environmental chamber. The purpose
of the study was to evaluate respiratory effects and irritation in asth-
matics at rest and during moderate exercise. At 0 ppm, eye irritation
was reported in 7% of the volunteers, odor was reported in 33% of
the volunteers, nasal irritation was reported in 20% of the volunteers,
and throat irritation was reported in 27% of the group (study d,
Figure 1). At 2.0 ppm, eye irritation was reported in 73% of the vol-
unteers, odor was reported in 100% of the volunteers, nasal irritation
was reported in 47% of the volunteers, and throat irritation was
reported in 33% of the group (study y, Figure 1). Formaldehyde con-
centrations were measured using a modified NIOSH chromotropic acid
method and by a hand-held Formaldemeter. The panel considered the
exposure data to be reliable. This study provides evidence that con-
centrations of 2.0 ppm for a period up to 40 min cause irritation
and that an OEL should be lower than 2.0 ppm, although this con-
centration has never produced serious acute or chronic adverse effects.
The authors concluded that in mild asthmatics, short-term exposure to
2.0 ppm formaldehyde under controlled conditions does not induce
acute airway obstruction. The panel observed that approximately 20%
of the volunteers exposed to 0 ppm reported irritation in the absence
of formaldehyde (possibly other agents in the indoor air were responsi-
ble) and that this response rate appears to be a typical background or
control rate for irritants (Holness et al., 1987, 1989).
Worker Surveys
Nineteen papers describing studies of occupational exposure were
evaluated, 15 of which are described here. Six of these papers were
considered particularly useful to setting an OEL. Several confirmed a
lack o f hyperreactivity of asthmatics to formaldehyde. Worker surveys
generally involve persons occupationally exposed to airborne formalde-
hyde or formaldehyde-containing materials for 8 h/d, 40 h/wk. Because
all workplaces contain concentrations of numerous air contaminants,
the panel considered workplace studies less definitive than chamber
studies where the concentration of formaldehyde is controlled.
Alexandersson et al. (1982) compared 47 subjects employe d a t a
carpentry shop who were exposed to 0.04–1.25 ppm formaldehyde
with 20 unexposed workers. The purpose of this study was to deter-
mine if irritant symptoms or changes in pulmonary function occurred
following continuous exposure to approximately 1.0 ppm formaldehyde.
Seventy-four percent of the exposed workers had eye discomfort and
36% had nose and throat irritation, whereas the controls reported no
irritation. The authors concluded that a slight deterioration in lung
function occurred after a day of industrial exposure to formaldehyde.
The deterioration seemed to be reversible and no chronic effects were
observed. The panel concluded that the information provided in the

paper was inadequate to reach meaningful conclusions about irritation
at low levels of exposure. There were not enough data nor was a
statistical evaluation presented to reach conclusions about subjective
symptoms or lung function that would assist in setting an OEL. Thus,
the panel did not consider the study relevant to setting an OEL, but
this study did provide information that formaldehyde is not very irritat-
ing to a significant fraction of workers at concentrations up to 1.25
ppm.
Alexandersson and Hedenstierna (1988) studied 38 employees who
were exposed to a mean formaldehyde concentration of approximately
0.4 ppm while working with acid-hardening lacquers. The results were
compared with 18 nonexposed persons working in the same company.
The purpose of the study was to determine irritative symptoms and
decrements in lung function associated with exposure to formaldehyde.
At 0 ppm, 17% responded with eye, nose, and throat irritation,
whereas 66% responded with irritation at 0.4 ppm. Of the 66%
responding at 0.4 ppm, 40% of these volunteers reported nasal irrita-
tion. The authors concluded that no changes in lung function occurred
and that formaldehyde emissions from acid-hardening lacquers could
cause irritation. Formaldehyde samples were collected by chemosorp-
tion, which is based on a reaction with 2,4-DNF. The formaldehyde
derivative is then desorbed and quantitated by means of liquid chro-
matography. Only three or four samples lasting 15 min were taken
during the day and were used as a basis for predicting the 8-h expo-
sure. It was assumed that the analytical method was sound (no refer-
ence cited), but the short sampling time and frequency provided only
approximate estimates of exposures.
Although this paper is often cited as being important to under-
standing the irritant hazard posed by formaldehyde, upon careful
review of this study, the panel considered the data too incomplete to
be useful. The authors did not evaluate specific concentrations at
which irritation occurred, as they only presented ranges of formalde-
hyde concentrations from which mean values were estimated. It can
be inferred, based on 17% of the respondents experiencing irritation
with no formaldehyde present, that other agents may be contributing
to the irritant symptoms or that, as noted previously, e ye irritation will
be reported despite the absence of an irritant in the environment.
Thus, the panel considered this study to be significant only in that it
suggested that a formaldehyde concentration below 1.0 ppm should be
adequate to protect workers. Since the authors only specified a range
of formaldehyde concentrations at which mean values were deter-
mined, the panel concluded that inferences about irritant effects at
specific concentrations cannot be made.
Alexandersson and Hedenstierna (1989) conducted a 5-yr follow-up
study of the carpentry shop worker study they performed in 1982.

The purpose of the study was to evaluate changes in lung function or
irritation in woodworkers exposed to formaldehyde over a 5-yr period.
The authors concluded that transient lung function impairment over a
workshift was caused by work-related formaldehyde exposure and that
effects were cumulative over time. However, impairment was reversed
within 4 wk of cessation of exposure. No details were offered con-
cerning methods of sampling and analysis. Based on the data provided,
the panel concluded that irritation occurred somewhere between 0.32
and 0.40 ppm. However, the panel did not agree with the authors’
conclusions that decrements in lung function occurred, since this
change was observed in only 1 out of 21 workers. In addition, since
significant concentrations of respirable dust were present, this con-
founder did not permit the authors to attribute any changes in lung
function solely to formaldehyde. An important finding was that irritant
effects associated with long-term exposure to formaldehyde (along with
other agents present as described in the study) were readily reversible.
Overall, the panel did not consider this study significant to setting an
OEL. Likewise, the TLV Committee did not rely heavily on it.
Bourne and Seferian (1959) evaluated dress shop workers who
reported irritation, particularly eye irritation, due to chemical off-gassing
from store merchandise. The objective of their work was to determine
whether formaldehyde was the causative agent. Although it was stated
that 0.13–0.45 ppm was present, no sampling results or method
description were presented. The authors stated only that the “air” was
tested for formaldehyde gas. It is probable, though not stated, that col-
orimetric tubes were used, and if so, the values would have low relia-
bility. The authors’ conclusion that a causal relationship exists between
formaldehyde exposure and irritation to the eyes, nose, and throat is
probably accurate but the concentrations are difficult to ascertain. The
panel did not consider this paper relevant to setting an OEL for
formaldehyde.
Gamble et al. (1976) conducted an epidemiological study compar-
ing rubber workers exposed to a phenol-formaldehyde-type resin to a
nonexposed (control) group. The purpose was to evaluate respiratory
function and irritation. The authors concluded that exposure to res-
pirable particulates and formaldehyde induced acute reversible effects
in pulmonary function. However, their findings are limited since many
chemicals exist in these work environments, and furthermore, formalde-
hyde levels were typically quite low. In light of the findings of
numerous other studies, the panel found it improbable that formalde-
hyde caused irritation at concentrations as low as 0.05 ppm. The
symptoms of the formaldehyde-exposed group were not significantly
different from the control group. The panel did not find this paper to
be relevant to setting an OEL for formaldehyde.
Holness and Nethercott (1989) compared 84 funeral service workers

reporting irritation when exposed to formaldehyde to 38 control sub-
jects. The purpose of this study was to determine the concentrations
where irritation did not occur. NIOSH method 125 (chromotropic acid)
using a single impinger containing sodium bisulfite solution was used
and was considered reliable. The average airborne concentration in this
study was 0.36 ± 0.19 ppm (approximately 0.4 ppm). Fifty percent of
the subjects reported eye irritation at 0.4 ppm and 55% of the con-
trols responded at 0 ppm. At 0.4 ppm, throat irritation occurred in
20% of the exposed subjects whereas 13% of the controls responded
with throat irritation. Fifty-two percent of the subjects responded with
nasal irritation at 0.4 ppm and 42% of the controls reported irritation
at 0 ppm. The authors concluded that embalmers exposed to formalde-
hyde were more likely to complain of eye and nose irritation than
those not exposed. Interestingly, the control group reported symptoms at
rates equivalent to, or greater than, the rate reported by the exposure
group. Thus, this study provides additional supporting information that
there is a relatively high incidence of eye irritation reported in control
populations. This study suggests that at 0.3 or 0.4 ppm formaldehyde,
the rate of eye irritation is no different from that reported by unex-
posed people.
Horvath et al. (1988) compared 109 workers potentially exposed to
airborne formaldehyde from particle board or molded products opera-
tions to 254 control subjects. The objective was to evaluate the
occurrence of acute and chronic effects on the mucous membrane
and lungs. Workers had been exposed 8 h/d, 40 h/wk for 10 yr. At
concentrations ranging from 0.4 to 3.0 ppm, there was no decrement
in FEV1. Between 0.4 and 1 ppm, 4% reported throat irritation and
24% reported eye irritation (study r, Figure 1). At greater than 1 ppm,
34% reported throat irritation and 50% reported eye irritation. Below
0.4 ppm there was no evidence of throat irritation. The NIOSH chro-
motropic acid method was used and the results were confirmed with
passive dosimeters. There was good agreement after applying a correc-
tion factor. The sampling and analytical methods were considered reli-
able. The authors concluded that formaldehyde is an eye irritant and
that it irritates mucous membranes at concentrations well below 3.0
ppm. They also concluded that permanent impairment to the respiratory
system did not occur following long-term exposure to 0.4 ppm. The
panel concluded that this study should have stated that “10 years of
exposure to 0.4 ppm formaldehyde produced no permanent respiratory
impairment or chronic respiratory effects.” The panel believes that the
slight across-shift pulmonary changes that were observed were likely
due to the combined presence of formaldehyde and other substances.
It is noteworthy, however, that Horvath et al. reported that throat irrita-
tion occurred in 4% of the population exposed to 0.4 and 1.0 ppm,
an incidence of irritation less than that usually reported in unexposed

persons.
Kilburn et al. (1989) evaluated chronic exposure to low concentra-
tions of formaldehyde and other solvents in 280 nonsmoking females
who had worked as histology technicians for 4 yr. The purpose of the
study was to determine if formaldehyde can cause decrements in pul-
monary function at concentrations of 0.2–1.9 ppm (with 5 ppm
peaks). Analytical measurements were conducted in 10 different labora-
tories. The sampling and analytical data were probably acceptable,
although no supporting data or information were provided. The authors
concluded that there may have been a small reduction in pulmonary
function, which might be attributable to formaldehyde or other sol-
vents. The panel considered this paper significant in providing evi-
dence that long-term exposure to formaldehyde concentrations less than
2.0 ppm does not produce chronic lung disease. In addition, there
was no evidence of any other serious acute or chronic health effects
from such exposures. These results were consistent with the study of
Horvath et al. (1988) that chronic exposure up to 2.0 ppm does not
cause adverse effects on pulmonary function.
Levine et al. (1984) conducted a survey and performed pulmonary
function tests on 90 morticians attending an educational workshop.
Sensory irritation was not evaluated. No chronic adverse effects were
observed between 0.2 and 1.2 ppm. The chromotropic acid method
was used to measure formaldehyde so the data were considered reli-
able. The authors concluded that intermittent exposure to low levels
(0.2–1.2 ppm) of formaldehyde produced no adverse effect on pul-
monary function. The panel concluded that these findings provided
additional evidence that formaldehyde does not produce chronic pul-
monary disease. These results were consistent with Horvath et al.
(1988), Kilburn et al. (1989), and Nunn et al. (1990).
Malaka and Kodama (1990) compared formaldehyde exposure and
the incidence of chronic obstructive pulmonary disease in plywood
workers exposed to 1.6–3.48 ppm (average was 2.36 ppm). The vol-
unteers had widespread respiratory disease and some had tuberculosis.
Respirable dust was present at 0.6 mg/m3 in the work environment.
Area and personal measurements of exposure were made by an “STC
Professional Formaldehyde Monitoring Kit” developed by Air Technology
Lab, Inc. The kit utilizes a passive dosimeter and a colorimeter. It i s
affected by other soluble aliphatic aldehydes, and by certain other
compounds not likely to be in the work environment. The authors
concluded that exposure to 1.13 ppm formaldehyde and 0.6 mg/m3
respirable dust produced a statistically significant induction of signs
and symptoms of chronic obstructive pulmonary disease. In the
exposed population, 53% reported cough and 44% reported phlegm,
while 32% and 18% of the controls, respectively, reported these. The
panel was concerned about the merit of the paper since these are
not typical symptoms of exposure to formaldehyde.
The panel decided that the preexisting respiratory infections and ill-
ness in the population studied by Malaka and Kodana (1990), combined
with the high concentration of dust, did not provide convincing evi-
dence that formaldehyde was the cause of these adverse effects. Further,
they noted that no statistically significant differences in the incidence of
obstructive pulmonary disease had been observed in this or previous
investigations. The panel also concluded that this study contained too
many confounding variables and lacked sufficient concentration-response
information to be useful. Since the study was conducted on groups suf-
fering widely from infectious diseases, it is difficult or impossible to
identify formaldehyde as the causal agent. One possible conclusion is
that the presence of formaldehyde may have aggravated, rather than
caused, the conditions reported. The panel did not consider this study
useful for setting an OEL. The panel considered the results of Malaka
and Kodama (1990) to be inconsistent with other studies that evaluated
the chronic pulmonary hazards posed by formaldehyde and concluded
that it was not the causal agent for the effects reported.
Nunn et al. (1990) investigated the long-term respiratory effects of
formaldehyde in 164 workers exposed during the production of urea
formaldehyde resin and compared them with 129 workers free of
formaldehyde exposure. The purpose of this study was to investigate
the long-term effects on the respiratory tract by examining symptoms
and lung function in workers exposed daily for 6 yr. The authors
concluded that no excess of respiratory symptoms or decline in lung
function was observed in this cohort at concentrations up to 2 ppm.
This paper presents sampling data collected over a 6-yr period using
2 different methods. Initially, samples were collected and analyzed by
the standard NIOSH chromotropic acid method, and subsequently the
so-called Hantzsch reaction. The Hantzsch reaction utilizes acetyl ace-
tone reagent, and is sensitive to formaldehyde, but also responds to
the presence of acetaldehyde and certain other compounds not likely
to have been present. In view of the many variables about which lit-
tle is known, the formaldehyde concentrations should be considered
descriptive in a general way but may have been slightly higher than
reported. The panel considered this study valuable based on the find-
ing that long-term effects are not apparent at exposures up to 2 ppm.
This study is consistent with Horvath et al. (1988), Kilburn et al.
(1989), and Levine et al. (1984), all of whom have shown that
formaldehyde does not produce chronic pulmonary disease.
Olsen and Dossing (1982) evaluated exposure to formaldehyde and
the incidence of irritation in 70 employees in 7 mobile day-care cen-
ters and 34 employees in 3 permanent day-care centers. The purpose
of this study was to evaluate the possible role of formaldehyde-con-
taining particle board in producing irritation. The mean formaldehyde

concentration was 0.35 ppm. Sampling was performed using a 1%
sodium bisulfite solution with evaluation by the chromotropic acid
method. Only area samples were collected, and these were of rela-
tively short duration. At 0.35 ppm, 55% of the mobile day-care center
workers experienced eye irritation, although the incidence of response
was not statistically significant. The control group responded with 15%
eye irritation to 0.06 ppm indoor formaldehyde concentrations. The
exposed subjects and controls reported higher levels of nose and
throat irritation (70% exposed vs. 25% controls) than eye irritation.
The authors concluded that a significantly higher frequency of irritation
to th e e yes and upper respiratory tract, unnatural dr owsiness,
headaches, menstrual irregularities, and use of analgesics was found in
the mobile day-care center workers exposed to 0.35 ppm formalde-
hyde than in employees in stationary buildings where 0.06 ppm
formaldehyde was present. The panel members did not consider this
paper useful in setting an OEL. They concluded that there was insuffi-
cient evidence to suggest that eye irritation occurred due to exposure
to formaldehyde, since no other well controlled studies even suggested
that any response could be seen at this concentration. The panel
believes that information previously disseminated to individuals working
in mobile trailers, which noted that formaldehyde was a sensory irri-
tant, may have biased their opinions in reporting irritant effects, thereby
producing an artifactual result.
Schoenberg and Mitchell (1975) evaluated airway disease and long-
term exposure to phenol-formaldehyde resin in 63 people who worked
at the same resin plant. Peak concentrations of 8.8–13.6 ppm were
measured with Draeger tubes, although the authors note that it was
“difficult to pinpoint the concentration.” The typical Draeger tube con-
centration was as low as 0.4–0.8 ppm according to the authors.
Irritation and excessive lacrimation occurred at concentrations of about
10 ppm. There was no indication that other contaminants were mea-
sured or accounted for. The authors concluded that small changes in
airway function were observed. Only limited sampling was conducted.
For example, it was reported that on one occasion three breathing
zone samples were collected in sodium bisulfite solution and thereafter
measured by titration with a standard iodine solution. This method
will determine formaldehyde, but other oxidizing and reducing agents
may influence the results. In short, the sampling data used in this
study must be considered qualitative in nature and not very reliable.
The panel concluded that not enough information was available in this
report to causally link exposure to formaldehyde with airway disease.
Shipkovitz (1968) conducted a survey of persons occupationally
exposed to formaldehyde in eight cutting and finishing plants in
Georgia and West Virginia to evaluate the relationship between reports
of irritation and typical workplace concentrations of formaldehyde.

Samples were collected in sodium bisulfite solution for short periods
of time, usually about 10 min. Thereafter, they were analyzed by the
ACGIH iodometric method. This method may be influenced by oxidiz-
ing or reducing substances present in the workplace, although it is
unlikely that appreciable quantities of such substances were present.
The sampling and analytical data should be considered of limited use-
fulness, primarily because of the very limited sampling time. This
study confirmed that formaldehyde is a sensory irritant and that
humans develop tolerance (adaptation) to the irritating effects produced
at low concentrations. The author concluded that the contemporaneous
TLV-CV was too high (5.0 ppm in 1968) and should be lowered.
Since no concentration-response data were presented, the panel con-
cluded that this study was of limited value.
Uba et al. (1989) conducted an evaluation of pulmonary function
and respiratory symptoms among 103 medical students exposed to
formaldehyde over a 7-mo period. The purpose was to determine the
incidence of bronchoconstriction and other effects following exposure to
typical concentrations of less than 1.0 ppm, with peak concentrations
less than 5.0 ppm. Irritation was observed in 40% of the volunteers at
approximately 1.2 ppm. There was no difference in sensitivity between
the healthy subjects and the asthmatics. The analytical methods were
reliable. The authors concluded that formaldehyde concentrations typi-
cally encountered in occupational and residential settings will not
usually cause significant bronchoconstriction even among subjects with
preexisting asthma. This study confirms previous papers that asthmatics
are not at increased risk when exposed to formaldehyde.
Community Surveys
Fifteen studies involving residents who lived in mobile homes or
households with formaldehyde containing materials were evaluated.
Because of the complex environment with many confounding factors,
including the likely presence of a number of airborn irritants, the data
are difficult to use for setting an OEL. Six of them are discussed
here; only 2 of the 15 were considered applicable. Table 3 and
Figure 1 present the concentration-response data from these two
mobile home exposure studies.
Anderson et al. (1983) conducted an epidemiologic study compar-
ing 100 mobile homes less than 3 yr old with 37 homes greater
than 3 yr old that had formaldehyde-containing materials. The cohort
was 288 residents of mobile homes in Wisconsin involving 53 adults
who answered a questionnaire pertaining to exposure and irritation.
The purpose of the study was to determine if there was a relationship
between formaldehyde concentrations in mobile homes and the reported
health status of residents. It was found that the newer homes had
higher levels of formaldehyde than the older homes. Irritation was

observed in 10% of the cohort at concentrations around 0.4 ppm,
and 24% of the responders experienced irritation at levels exceeding
0.4 ppm (study k *, Figure 1). Fifty-six percent of the people exposed
to greater than 0.8 ppm experienced some upper respiratory irritation
(study p*, Figure 1). Of these 53 adults, 37% of the 288 participants
were smokers and 36% had a history of allergy. The authors concluded
that eye and nasal irritation were more prevalent among those from
households with formaldehyde levels above 0.8 ppm than among
those from the homes with concentrations less than 0.4 ppm. A large
number of measurements were made using NIOSH method 125 (chro-
motropic acid), modified to include collection in sodium bisulfite solu-
tion. These methods were considered reliable. The panel considered
Anderson et al. (1983) useful to setting an OEL since only 10% of
the 288 persons experienced irritation at concentrations close to 0.40
ppm (8–24 h/d). This suggests that a large fraction of the population
is likely to be free of irritation at concentrations below 0.4 ppm even
if exposed continuously for 24 h/d.
Bracken et al. (1985) compared data from a questionnaire adminis-
tered to 54 residents living in 22 UFFI homes, to 26 residents living
in 16 noninsul ated homes, and to 10 pathology technicians employed
in different workplaces. The purpose of this study was to determine
whether there was a relationship between irritative symptoms and air-
borne concentrations of formaldehyde. The average concentration in the
UFFI homes was 0.054 ppm, whereas the average level in the control
homes was 0.051 ppm. The hospital pathology technicians were occu-
pationally exposed to formaldehyde at concentrations ranging from
0.02 to 2.7 ppm. Nonspecific symptoms were recorded more often in
the UFFI subjects than in the laboratory technicians, even though the
latter were exposed to formaldehyde concentrations more than twice
those of the UFFI homes. The UFFI residents reported a higher inci-
dence of nasal symptoms, headaches, and throat irritation than the
other groups. The authors found no changes in pulmonary function
that could be attributed to formaldehyde in any of the groups and
concluded that these results indicate that no hazard exists at 0.054
ppm. In this study, area samples were collected and analyzed accord-
ing to the standard NIOSH method. Personal monitoring was accom-
plished by using the DuPont Proco-Tek series II, type C-60 Badges. It
was concluded that the sampling and analytical data were acceptable.
The panel concluded that this paper contained useful information.
Although UFFI residents complained of nonspecific irritant symptoms,
formaldehyde could not be identified as the causative agent. UFFI resi-
dents may have been biased by publicity regarding the irritation hazard
posed by airborne formaldehyde. Although, the concentrations were too
low to be useful for setting an OEL, it was interesting to note that
the technicians who were typically exposed to higher concentrations of

formaldehyde than the UFFI residents reported a lower frequency of
irritation.
Frigas et al. (1981) presented a case report of a 47-yr-old woman
who developed severe steroid-resistant asthma during the year after she
insulated her farm home with UFFI. Bronchial provocation tests with 3
ppm formaldehyde were conducted to determine if formaldehyde was
the cause of the asthma. Concentrations of formaldehyde in the home
were not determined. The results were negative and the authors con-
cluded that formaldehyde was not the causal agent. The panel con-
cluded that it was noteworthy that a person with severe asthma did
not react to bronchial provocation by formaldehyde.
Hanrahan et al. (1984) conducted a study of 65 households from
a group of 208 mobile homes. Formaldehyde concentrations measured
inside the mobile homes ranged from 0.10 to 0.80 ppm. The chro-
motropic acid method with collection in sodium bisulfite absorbing
reagent was used. The authors concluded that there was a positive
relationship between formaldehyde concentrations and ocular discom-
fort. The panel concluded that it was difficult to determine whether a
concentration-response relationship existed between eye irritation and
formaldehyde, or if other sensory irritants present in most mobile
homes were responsible for the irritation. No chemical other than
formaldehyde was measured. Due to the lack of specific data, no dis-
cussion of confounding variables, and no control group, this paper
was of limited value.
Nordman et al. (1985) studied 230 persons referred to the Institute
of Occupational Health from different regions of Finland because they
were suspected of having formaldehyde-induced bronchial asthma.
These persons had been exposed to formaldehyde via resins, glues,
solutions, and detergents. The purpose of this study was to determine
if asthma-related symptoms could be attributed to formaldehyde.
Twelve of the 230-person cohort (5.2%) were found to be sensitized
to formaldehyde based on the results of a bronchial provocation test
at 0.96 and 2.0 ppm. Eleven of the 12 persons reacted to 2.0 ppm
and only one reacted to 0.96 ppm. No measurements of airborne
formaldehyde were made in the various persons’ workplaces. The
authors concluded that although formaldehyde may cause asthma in
some individuals , this is an extremely rare occurrence. Based on this
and the papers published by others, the panel agreed with the
authors’ conclusions. Asthmatic symptoms are not expected in workers
until concentrations are much higher than would be acceptable to
most workers. This paper reinforced the panel’s view that formaldehyde
is not a hazard to asthmatics at concentrations below 2.0 ppm.
Ritchie and Lehnen (1987) conducted a survey of nearly 2000 res-
idents living in 397 mobile homes and 494 conventional homes to
compare the incidence of irritation. The purpose was to determine if

formaldehyde concentrations greater than 0.1 ppm (24 h/d) posed a
significant health hazard. Formaldehyde was collected and measured
using NIOSH method 125, but only a single impinger containing dis-
tilled water was used. It is probable, therefore, that results reported
are somewhat lower (perhaps 10–20%) than the actual concentrations.
Eye irritation was reported in 90% of the subjects who were exposed
to 0.3 ppm or greater in mobile homes (study j*, Figure 1). Between
0.1 and 0.3 ppm, 12–32% responded with eye irritation (study i*,
Figure 1). Below 0.1 ppm, 1–2% reported eye irritation. For nose and
throat irritation, 74–99% responded at 0.3 ppm and above, 12% to
36% responded at 0.1–0.3 ppm, and 11% responded at concentrations
below 0.1 ppm. The rate of response in nonexposed persons was
20% for nose and throat irritation and 1–2% for eye irritation. The
authors concluded that the concentrations of formaldehyde in mobile
and conventional homes were consistent with those reported in other
studies. Eye, nose, and throat irritation were reliably reported only at
concentrations of 0.1 ppm and above for exposures of 16–24 h/d.
The panel considered this to be a useful study; however, there was
concern that confounders such as smoking and indoor air contami-
nants contributed to irritation and artificially increased the incidence of
reported symptoms at the lower concentrations. For example, the
active smokers reported higher levels of eye irritation than the non-
smoking respondents.
Cancer Hazard
Although the panel was not charged to evaluate formaldehyde’s car-
cinogenicity, we wanted to assure ourselves that our recommendation
to prevent irritation would not present a cancer hazard (Monticello et
al., 1996). Formaldehyde has been shown to produce nasal tumors in
rats exposed 6 h/d for 1 yr or more to 10 and 15 ppm (Gibson,
1983). This concentration is about 30–50 times greater than the TLV-
CV (0.3 ppm) adopted by the ACGIH (1991). The panel concluded
that an OEL-TWA (8 h) of 0.3 ppm and OEL-CV of 1.0 ppm will
also protect workers from the cancer hazard. This opinion is based on
the biological factors involved in formaldehyde carcinogenesis.
Specifically, most scientists currently believe that the mechanism of
action that is likely to have produced the nasal tumors involves
repeated cytotoxicity. This mechanism is not accounted for in current
low-dose risk models such as the linearized multistage model (Starr,
1990).
Nasal cancers have only been induced in rats exposed to 10 and
15 ppm, and at these concentrations there is a 4- to 10-fold increase
in cell proliferation (Monticello & Morgan, 1996). It has been shown
that the major pathway for detoxification in the rat will be saturated at
10 ppm. At concentrations above 10 ppm, there is at least a seven-

fold greater level of formation of DNA–protein cross-links per ppm of
exposure than what occurs at lower concentrations (Casanova & Heck,
1991). Formaldehyde-induced nonneoplastic responses, such as inhibi-
tion of mucociliary function, epithelial degeneration, inflammation,
squamous metaplasia, and increased cell proliferation, correlate well
with the site-specific uptake patterns and disease patterns seen in test
animals. Other biological factors should further reduce the risk of can-
ce r at l ow concentrations, including more efficient remova l o f
formaldehyde by the mucocilliary clearance apparatus and DNA repair.
Thus, there is a cascade of protective reactions that appear to be ade-
quate at concentrations below 3.0 ppm (Starr & Buck, 1984) to pre-
vent a cancer hazard. This is evident in animal studies since no
changes in cell proliferation or nasal toxicity have been seen at con-
centrations below 2.0 ppm (Gibson, 1983; Monticello et al., 1996).
Since these events are considered essential for the induction of nasal
tumors by formaldehyde, an OEL of 0.3 ppm should protect workers
against the potential cancer hazard (Monticello et al., 1996; Conolly
et al., 1995). The panel agreed with the conclusion reached by the
ACGIH TLV Committee as described in their documentation, “. . . inter-
pretation of the biologically based animal cancer risk assessment data
indicate that the oncogenic potential of formaldehyde is a threshold
phenomenon and that prevention of upper respiratory irritation and the
associated regenerative hyperplasia should eliminate, for all practical
purposes, any excess risk posed by occupational formaldehyde expo-
sure alone” (ACGIH, 1991).
Further support for this position is provided by the lack of a ny
consistent epidemiologic evidence that formaldehyde has produced an
increased incidence of cancer eve n i n workers exposed to much high-
er concentrations than those recommended by the ACGIH or this
panel (Levine, 1984). Although not available at the time that the
panel met, the most recent epidemiology study o f workers, considered
by many to be the one having the best exposure data and informa-
tion on the cause of death, showed no increased cancer risk
(Andjelkovich et al., 1995a, 1995b; McLaughlin, 1994; Blair et al.,
1986).
DISCUSSION
After evaluating approximately 150 articles that addressed formalde-
hyde, the panel decided that 18 of the studies were particularly useful
for deriving an occupational exposure limit (OEL) intended to prevent
irritation. Based on these papers, the panel reached a number of opin-
ions. First, the panel concluded that asthmatics were not particularly
sensitive to the airway effects of formaldehyde. At least four studies
suggested that asthmatics respond to formaldehyde like nonasthmatics.

The works of Green et al. (1987) and Sauder et al. (1986, 1987),
which compared the irritative responses at various concentrations in
healthy subjects and asthmatics, were considered the most relevant
studies. Sheppard et al. (1986) and Witek et al. (1987) also found
that asthmatics were not particularly sensitive to formaldehyde. The
panel concluded that, based on the available data, bronchoconstriction
will only occur at concentrations greater than 2 ppm and that asth-
matics were no more sensitive than others to formaldehyde.
Second, the panel concluded that the most sensitive adverse effect
of formaldehyde is eye irritation. Ideally, when suggesting an OEL, suf-
ficient information should be available to understand the percent of
the exposed population that experiences irritation at various airborne
concentrations. In an attempt to build a concentration-response rela-
tionship for eye irritation in humans, the panel identified the studies
that could potentially be used (listed in Table 3). A linear concentra-
tion-response relationship is presented in Figure 1. The possibility that
an S-shaped curve could also exist was also considered. As can be
expected when using results from a wide variety of exposure settings
and exposure duration, there is much scatter on this plot. Neverthe-
less, there is an increase in eye irritation, above background, with
increasing concentration beyond about 1.0 ppm. As noted in a num-
ber of studies involving volunteers exposed to an eye irritant, the Y
intercept at zero concentration is about 15–20% [e.g., this is a typical
level of eye irritation observe d in volunteer studies (and often in the
public)]. As such, it is usually not possible to attribute an irritation
response to the test chemical below this response level.
The two studies with the lowest concentrations above zero [i (0.2
ppm) and h (0.24 ppm) in Figure 1] reported a percent response sim-
ilar to background or zero exposure concentration. The next studies [j
(>0.3 ppm), l (0.35 ppm), k (0.4 ppm), and n (0.5 ppm) in Figure 1]
reported results from zero to 90% response, the widest range of
response. Even at 3 ppm there is a wide range of response, from 23
to 100% and these were all similar studies in well-controlled experi-
mental settings. Thus, the panel drew the general conclusion that
between 0 and 0.3 ppm there is no increase in eye irritation above
a general background level of around 10–20%. An important factor
contributing to the scatter of data in Figure 1 is that the dosimetric
“percent response” does not address the intensity of the response and,
obviously, the definition of a response for eye irritation is impossible
to standardize across such studies. Nevertheless, a general trend is
apparent and can be used to identify an OEL.
Third, the panel concluded that based on the weight of evidence
from this analysis, and that of others who have evaluated eye irritation,
reports of irritation below 0.3–0.5 ppm formaldehyde were too unreli-
able to attribute the irritation solely to formaldehyde. The basis for this
statement is that there were no data from well-controlled studies that
indicate that continuous exposure for 0.5, 3, or 6 h to 0.3 ppm can
produce irritation. The panel found support for its view that responses
in this range are not reliable since in several studies respondents com-
plained of irritation when exposed to 0.3 ppm at the same frequency
as when they were exposed to clean air. These response rates were
not unusual compared to data from 3 of the 11 controlled human
studies (Kulle, 1993; Sauder et al., 1987; Witek et al., 1987) in which
irritation was reported at 0 ppm formaldehyde.
Fourth, the panel decided that there was no good evidence to
conclude that formaldehyde poses a chronic pulmonary hazard such
as emphysema or COPD. Five studies clearly show a lack of COPD
hazard. For example, Horvath et al. (1988) concluded that long-term
chronic pulmonary effects will not occur at concentrations between
0.4 and 3.0 ppm. Kilburn et al. (1989) and Nunn et al. (1990) pre-
sented evidence supporting the results of Horvath et al. that at con-
centrations up to 2.0 ppm, chronic obstructive pulmonary disease will
not occur. This conclusion was further supported by the work of
Levine et al. (1984). Uba et al. (1989) later showed that even at
concentrations high enough to cause sensory irritation, asthmatics do
not suffer from bronchoconstriction or any other respiratory symptoms.
Fifth, the panel found most of the community and indoor air studies
to be of minimal usefulness in setting an OEL but that some insight
could be gained about the eye irritation hazard. For example, Ritchie
and Lehnen’s (1987) study was noteworthy because it involved nearly
2000 persons and because they reported a 12–32% frequency of eye
irritation at concentrations of 0.1–0.3 ppm (8–24 h/d exposure). They
indicated that 90% of the exposed population reported irritation at
concentrations greater than 0.3 ppm. However, these results are incon-
sistent with results of controlled human studies (Table 3); thus the
panel believes that other chemicals, not detected or measured, con-
tributed to or caused the irritation, or, more likely, that the back-
ground incidence of eye irritation made the results for concentrations
below 0.3 ppm invalid.
The panel acknowledged that it is possible that continuous expo-
sure (24 h/d) might increase the frequency of response in the diverse
population of people exposed in mobile homes. For example,
Anderson et al. (1983) reported eye irritation in 56% of the persons
exposed to greater than 0.8 ppm and 24% reported eye irritation at
concentrations greater than 0.4 ppm. Based on the available data, the
panel concluded that although concentrations below 0.1 ppm in the
residential setting have been reported to cause minor irritant effects in
humans, based on the data obtained in volunteer studies, it is likely
that this level of response was attributable to other environmental fac-
tors, the background incidence of eye irritation, self-selection bias, or

the effects of interviewer interaction.
Sixth, the panel concluded that for most persons, eye irritation
occurs at lower concentrations than that needed to produce nose and
throat irritation. The studies of Bender et al. (1983), Andersen and
Molhave (1983), and Kulle (1993), which assessed the human response
to concentrations below 1.0 ppm, were the foundation for this view.
Andersen and Molhave showed that about 20% of the 16 persons
reported eye irritation at 0.24 ppm. Discomfort was observed with
increasing dose (even for smokers). Interestingly, due to acclimation,
61% of the volunteers reported no further increase in irritation at 0.81
ppm. Bender et al. (1983) showed that the eye could detect formalde-
hyde at 0.35 ppm in about 42% of 12 volunteers, but the authors
acknowledged that detection did not always lead to irritation. Kulle
(1993) found that none of the 19 volunteers reported eye irritation at
0.5 ppm; however, 26% of them reported eye irritation at 1.0 ppm.
The panel acknowledged that the results of studies involving generally
healthy, relatively young, volunteers may not reflect the range of
results that would be observed if perhaps 100 workers of varying age
and health status underwent the same testing.
Seventh, the panel concluded that in chamber studies, and proba-
bly in other study conditions, some of the irritant responses reported
by volunteers exposed to concentrations of 0.3 ppm or less were just
as likely to occur during exposure to clean air. This may well explain
the bulk of the differences between this panel’s interpretation of the
published data and that of the TLV Committee. The panel was con-
vinced that results of studies involving formaldehyde, as well as the
results of numerous other studies of eye and nose irritants, clearly
show that response rates below 20% are very near the background
level of eye and nasal irritation reported among those in the general
population. Consequently, results from volunteer studies at this level of
response cannot be attributed to exposure to a specific contaminant.
Numerous other studies of other chemical irritants confirm this view. I t
is unclear whether this subtlety in interpreting these types of studies
was recognized by the TLV Committee.
Eighth, the panel concluded that based on the concentration-response
curve derived from human studies (Figure 1), it is possible that as many
as 5–25% of workers could report eye irritation somewhere between 0.5
and 1.0 ppm following 15 min to 6 h of exposure (although responses
below 20% are often not considered attributable to formaldehyde alone).
They also noted that many of the studies showed that in the presence
of other chemicals, as well as airborne dust, there may be an increased
susceptibility to formaldehyde’s irritant effects.
Ninth, the panel concluded that based on the weight of evidence,
an OEL-TWA of 0. 3 ppm was a concentration that would protect nearly
all workers, except perhaps the 95th to 99th percentile person, from
transient eye irritation. In addition, the data indicated that eye irritation
does not become significant until a concentration of at least 1.0 ppm is
reached and, based on most studies, for most people this level of irri-
tation rapidly subsides. Therefore, 1.0 ppm was determined to be an
acceptable ceiling value (CV) for periods up to 15 min in duration
and this is not expected to cause any eye irritation in at least 75% of
the workers (Figure 1 and Table 3). An OEL-CV of 1.0 ppm is the
maximum concentration to which people may be exposed. The panel
acknowledged that the primary bases for their recommendations were
the controlled human studies, since other data suffered from numerous
possible confounding factors.
Basis for an OEL
The rationale for the OELs recommended by the panel (8-h TWA)
and CV is as follows:
At 3.0 ppm, in environmental chamber studies, Kulle et al. (1987)

and Kulle (1993) reported that 100% of the people have eye irrita-
tion, whereas Sauder et al. (1986, 1987) reported eye irritation in
70% of healthy volunteers and in 78% of the asthmatics at this
concentration. In addition, Horvath et al. (1988) identified no
adverse effects on pulmonary function at 3.0 ppm following chronic
exposure.
At 2.0 ppm, in environmental chamber studies, Kulle et al. (1987)
and Kulle (1993) observed 53% eye irritation (32% had mild eye
irritation and 21% had moderate irritation). Schachter et al. (1987)
found that 47% of workers exposed to 2.0 ppm formaldehyde in a
controlled environment had eye irritation, whereas 50% of healthy
individuals had these symptoms (Schachter et al., 1986). Witek et
al. (1987) saw eye irritation in 73% of the asthmatic test popula-
tion at 2.0 ppm, and Weber-Tschopp et al. (1977) reported an
increased eye blink rate in 33% of the subjects at 2.1 ppm.
At 1 ppm, in environmental chamber studies, Kulle et al. (1987) and
Kulle (1993) found that 26% of volunteers reported eye irritation.
Above 0.8 ppm, Andersen et al. (1983) reported that 56% of the
respondents had eye irritation and Alexandersson and Hedenstierna
(1988) reported 66% responding between 0.3 to 0.4 ppm. Kulle et
al. (1987) and Kulle (1993) found no eye irritation at 0.5 ppm fol-
lowing exposures as long as 3 h, and both Kulle (1993) and
Schachter et al. (1986, 1987) saw 5% and 0% eye irritation, respec-
tively, at 0 ppm. At 0.24 ppm formaldehyde, Andersen and Molhave
(1983) reported eye irritation in 19% of their subjects. Ritchie and
Lehnen (1987) found eye irritation in 90% of their cohort at 0.3
ppm formaldehyde or greater, but the sampling methods used likely
underestimated the actual concentration of formaldehyde. In addition,

confounders such as age, smoking, and the presence of other indoor
air contaminants may have artificially increased their reported inci-
dence of eye irritation. The panel did not give as much weight to
indoor air studies compared to environmental chamber studies, since
exposure to low concentrations of other irritants was possible and
these could not be accounted for.
Based on the weight of evidence from chamber studies (Figure 1),
the panel concluded that approximately 50% of workers will report
eye irritation attributable to formaldehyde at 2.0 ppm, 25% at 1.0
ppm, and few, if any, will report eye irritation at 0.5 ppm if
exposed for periods of 3–8 h. The panel recognized that few studies
carefully evaluated concentrations below 0.5 ppm. For example,
Andersen and Molhave (1983) reported that 19% of respondents
experienced eye irritation at 0.24 ppm. Only 3 other studies exam-
ined the response to formaldehyde at concentrations below 1.0 ppm.
Bender et al. (1983) reported eye irritation in 42% of the volunteers
at 0.35 ppm and in 54% at 0.56 ppm. Although these findings
were significant, the information is more applicable to setting a CV
or STEL since persons were exposed for only 6 min and there were
some questions regarding the study. Kulle (1993) observed no irrita-
tion at 0.5 ppm and did not observe eye irritation until 1.0 ppm
formaldehyde, at which point 26% of the healthy volunteers reported
irritation. This study would have been more useful for predicting
the response of workers if persons other than young adults had
been studied and more subjects were involved, but, nonetheless, it
was considered the best designed and most reliable study. Based
on the weight of evidence from these studies, the panel concluded
that the best estimate for the lowest observable effect level (LOEL)
for humans was less than 0.3 ppm for 3–8 h of exposure. The
work of Anderson et al. (1983) suggested that an environmental
limit as high as 0.3–0.4 ppm for a 24-h exposure period might
protect 90% of the population from irritation.
Based on the weight of data from the controlled human studies and
the epidemiological surveys, the panel concluded that at 0.3 ppm or
less, no irritation attributable to formaldehyde should occur, e ven if
people are exposed 8 h/d.
Rationale for an 8-h OEL and a CV
The information provided in more than 100 papers led the panel
to conclude that for periods of 3–8 h/d, eye irritation was concentra-
tion, rather than concentration times time, dependent. In general, the
toxicology community have embraced this view for the irritant response
(Andersen et al., 1987). The data on formaldehyde support the tenet
that irritation is a threshold- and time-independent response since expo-

sure to concentrations of 0.3 ppm or lower failed to produce irritation
(above background) following either 10 min or 6 h of exposure.
A ceiling value (CV) has traditionally been recommended when
very brief exposures above a specific concentration have been shown
(or can be expected) to cause adverse health effects. Rather than the
CV of 0.3 ppm selected by the TLV Committee, the panel decided a
ceiling value of 1.0 ppm was appropriate to prevent moderate, albeit
transient, eye irritation. The panel decided that a CV of 1.0 ppm was
likely to protect at least 75% and perhaps as much as 95% of the
working population. The panel was aware that some of the data show
that volunteers exposed to pure formaldehyde at concentrations less
than 1.0 ppm for 8 h or less sometimes reported irritation at about
the same frequency a s when exposed to clean ambient air. The panel
recognized that there is some uncertainty in the margin of safety
inherent in this OEL since the basis is derived from relatively small
studies of healthy volunteers.
Because of the large number of persons who are occupationally
exposed to formaldehyde each day, and because the air inevitably
contains low concentrations of particulates and at least background
concentrations of other gases and vapors, an OEL less than 0.5 ppm
may be needed to prevent irritation in a diverse working population.
Consequently, with the intent of protecting nearly everyone from irrita-
tion, the panel recommended an OEL of 0.3 ppm (8-h TWA). Higher
workplace concentrations, including 1.0 ppm, may well not produce
eye irritation in most workers and therefore some agencies may
choose to protect a smaller segment of the population than that pro-
tected by the TLV or our recommended OEL-TWA. For example, the
current OSHA permissible exposure limit (PEL) is 0.75 ppm.
The recommendations of the panel are consistent with those indi-
cated by toxicological models for predicting TLVs for irritants (Kane &
Alarie 1977; Kane et al. 1979), and they are consistent with the
ACGIH TLV Committee’s goal to protect nearly all workers. The panel
noted that if concentrations of formaldehyde are kept below 0.1 ppm in
the indoor environment (where exposure can occur 24 h/d) this should
prevent irritation in virtually all persons.
REFERENCES
Adams, D. O., Hamilton, T. A., Lauer, L. D., and Dean, J. H. 1987. The effect of formaldehyde
exposure upon the mononuclear phagocyte system of mice. Toxicol. Appl. Pharmacol.
88:165–174.
Alarie, Y. 1981. Dose-response analysis in animal studies: prediction of human responses.
Environ. Health Perspect. 42:9–13.
Alarie, Y., and Luo, J. E. 1986. Sensory irritation by airborne chemicals: A basis to establish
acceptable levels of exposure. In Toxicology of the nasal passages, ed. C. S. Barrows, pp.
91–100. New York: Hemisphere.
*Alexandersson, R., and Hedenstierna, G. 1988. Respiratory hazards associated with exposure to
formaldehyde and solvents in acid-curing plants. Arch. Environ. Health 43:222–227.
*Alexandersson, R., and Hedenstierna, G. 1989. Pulmonary function in wood workers exposed to
formaldehyde: A prospective study. Arch. Environ. Health 44:5–11.
*Alexandersson, R., Kolmodin-Hedman, B., and Hedenstierna, G. 1982. Exposure to formaldehyde:
Effects on pulmonary function. Arch. Environ. Health 37:279–284.
*Altshuller, A. P., Miller, D. L., and Sleva, S. F. 1961. Determination of formaldehyde in gas
mixtures by the chromatropic acid method. Anal. Chem. 33:621–625.
*American Conference of Governmental Industrial Hygienists. 1972. Documentation of the
Threshold Limit Value. Documentation for 1972. Cincinnati, OH: ACGIH.
Threshold Limit Values. Documentation for 1980. Cincinnati, OH: ACGIH.
American Conference of Governmental Industrial Hygienists. 1981. Documentation of the
Threshold Limit Values. Documentations for 1981. Cincinnati, OH: ACGIH.
American Conference of Governmental Industrial Hygienists. 1982. Protection of the sensitive indi-
vidual. Annals of the ACGIH. Cincinnati, OH: ACGIH.
American Conference of Governmental Industrial Hygienists. 1983. Documentation of the
American Conference of Governmental Industrial Hygienists. 1990a. Threshold limit values: A
more balanced appraisal. Appl. Occup. Environ. Hyg. 5:340–344.
American Conference of Governmental Industrial Hygienists. 1990b. 1989 Supplementation docu-
mentation—Formaldehyde. Appl Occup. Environ. Hyg. 5:383–389.
*American Conference of Governmental Industrial Hygienists. 1991. Formaldehyde. In Documenta-
tion of the threshold limit value and biological exposure limits, 6th ed., pp. 664–688. Cincinnati,
OH: ACGIH.
*American Conference of Governmental Industrial Hygienists. 1995. Threshold Limit Values for
Chemical Substances and Physical Agents and Biological Exposure Limits, pp. 1–128.
Cincinnati, OH: ACGIH.
American Industrial Hygiene Association (AIHA). 1989. Occupational Exposure and Work Practice
Guidelines for Formaldehyde. Akron, OH: AIHA.
American Public Health Association (APHA). 1991. Health Based Exposure Limits and Lowest
National Occupational Exposure Limits. Draft version 5, November 6. Washington, DC:
APHA.
*American Standards Association (ASA). 1944. Allowable Concentrations of Formaldehyde.
Publication 237.16-1944. New York: ASA.
*Andersen, I., and Molhave, L. 1983. Controlled human studies with formaldehyde. In
Formaldehyde toxicity, ed. J. E. Gibson, pp. 154–165. Washington, DC: Hemisphere.
*Andersen, I., Lundquist, G. R., Jensen, P. L., and Proctor, D. F. 1974. Human response to con-
trolled level of sulfur dioxide. Arch. Environ. Health 28:31–36.
*Andersen, M. E., MacNaugh ton, M. G., Clewell, H. J. III, and Paustenbach, D. J. 1987.
Adjusting exposure limits for long and short exposure periods using a physiological pharma-
cokinetics model. Am. Ind. Hyg. Assoc. J. 48:335–343.
*Anderson, H. A., Dally, K. A., Hanrahan, L. P., Eckman, A. D., and Kanarek, M. S. 1983. The
Epidemiology of Mobile Home Formaldehyde Vapor Concentration and Residents’ Health
Status. U.S. Environmental Protection Agency (USEPA) pub. 905/1-83-001, Washington, DC.
*Andjelkovich, D. A., Janszen, D. B., Brown, M. H., Richardson, R. G., and Miller, F. J. 1995a.
Mortality of iron foundry workers: IV. Analysis of a subcohort exposed to formaldehyde. J.
Occup. Environ. Med. 37:826–837.
*Citation not discussed in text.

*Andjelkovich, D. A., Janszen, D. B., Conolly, R. B., and Miller, F. J. 1995b. Formaldehyde
exposure not associated with cancer of the respiratory tract in iron foundry workers: A syn-
opsis of ciit epidemiologic findings. CIIT Activities 15:1–12.
*Bender, J. R., Mullin, L. S., Graepel, G. J., and Wilson, W. E. 1983. Eye irritation response of
humans to formaldehyde. Am. Ind. Hyg. Assoc. J. 44:463–465.
Blair, A., Stewart, P., O’Berg, M., Gaffey, W. 1986. Mortality among individual workers exposed
to formaldehyde. J. National Cancer Institute 76:1071–1084.
Böhmer, K. 1934. Formalin poisoning. Dtsch. Z. Gesamte. Gerichtl. Med. 23:7018.
*Bourne, H. G., and Seferian, S. 1959. Formaldehyde in wrinkle-proof apparel produces—Tears
for milady. Ind. Med. Surg. 28:232–238.
Bowditch, M., Drinker, D. K., Drinker, P., Haggard, H. H., and Hamilton, A. 1940. Code for
safe concentrations of certain common toxic substances used in industry. J. Ind. Hyg. and
Tox. 22:251–259.
Boysen, M., Zadig, E., Digernes, V., Abeler, V., and Reith, A. 1990. Nasal mucosa in workers
exposed to formaldehyde: A pilot study. Br. J. Ind. Med. 47:116–121.
*Bracken, M. J., Leasa, D. J., and Morgan, W. K. 1985. Exposure to formaldehyde: Relationship
to respiratory symptoms and function. Can. J. Public Health 76:312–316.
*Breysse , P. A. 1981. The health cost of “tight” homes. J. Am. Med. Assoc. 245:267–268.
Breysse, P. A. 1991. ACGIH TLVs: A critical analysis of the documentation. Am. J. Ind. Med.
20:423–428.
Broder, C. P., Brasher, P., Cole, P., Lipa, M., Mintz, S., and Nethercott, J. R. 1987. Comparison
of health of occupants of control homes and homes insulated with urea formaldehyde foam
before and after corrective work. Indoor Air 2:605–609.
Broder, I., Corey, P., Cole, P., Lipa, M., Mintz, S., and Nethercott, J. R. 1988. Comparison of
health occupants and characteristics among control homes and homes insulated with urea
formaldehyde foams. Parts I, II, III. Environ. Res. 45:141–203.
Bus, J. S., and Gibson, J. E. 1985. Body defense mechanisms to toxicant exposure. In Patty’s
industrial hygiene and toxicology, vol. 3B, eds. L. Crally and L. Cralley, pp. 143–174. New
York: John Wiley and Sons.
Butterworth, B. E., Conolly, R. B., and Morgan, K. T. 1995. A strategy for establishing mode of
action of chemical carcinogens as a guide for approaches to risk assessments. Cancer Lett.
93:129–146.
Cain, W. S., See, L. C., and Tosun, T. 1986. Irritation and Odor from Formaldehyde: Chamber
Studies, pp. 126–132. American Society of Heating, Refrigerating, and Air Conditioning
Engineers.
Calabrese, E. J. 1985. Toxic susceptibility: Male and female differences. New York: John Wiley and
Sons.
*California Air Resources Board. 1991. Proposed Identification of Formaldehyde as a Toxic Air
Contaminant—Preliminary Draft. February. Sacramento, CA: CARB.
Casanova, M., and Heck, H. d’A. 1987. Further studies of the metabolic incorporation and cova-
lent binding of inhaled [3H] a nd [14C] formaldehyde in rat nasal mucosa. Toxicol. Appl.
Pharmacol. 89:105–121.
*Casanova, M., and Heck, H. d’A. 1991. The impact of DNA-protein cross linking studies on
quantitative risk assessment of formaldehyde. CIIT Activities Bull. 11:1–6.
Castleman, B. I., and Ziem, B. E. 1988. Corporate influence on threshold limit values. Am. J.
Ind. Med. 13:531–559.
*Chang, J. C. F., Steinhagen, W. H., and Barrow, C. S. 1981. Effect of single of repeated
formaldehyde exposure on minute volume of B6C3F1 mice and F-344 rats. Toxicol. Appl.
*Chang, J. C. F., Gross, E. A., Swenberg, J. A., and Burrow, C. S. 1983. Nasal cavity deposi-
tion, histopathology, and cell proliferation after single or repeated formaldehyde exposures in
B6C3F1 mice and F-344 rats. Toxicol. Appl. Pharmacol. 68:161–176.

Cockcroft, D. W., Hoeppner, V. H., and Dolovich, J. 1982. Occupational asthma caused by
cedar urea formaldehyde particleboard. Chest 82:49–53.
Coldiron, V. R., Ward, J. B., Trieff, N. M., Janssen, H. E., and Smith, J. H. 1983. Occupational
exposure to formaldehyde in a medical center autopsy service. J. Occup. Med. 25:544–
548.
*Conlon, P. C., and Mason, A. M. 1984. Emergency action guide for formaldehyde solution.
Washington, DC: Association of American Railroads.
*Conolly, R. B., Andjelkovich, D. A., Casanova, M., Heck, H., Janszen, D. B., Kimbell, J. S.,
Morgan, K. T., and Recio, L. 1995. Multidisciplinary, iterative examination of the mechanism
of formaldehyde carcinogen icity: The basis for better risk assessment. CIIT Activities 15:1–
16.
*Cook, W. A. 1945. Maximum allowable concentrations of industrial contaminants. Ind. Med.
14:936–946.
*Cook, W. A. 1986. World-Wide Occupational Exposure Limits. Akron, OH: American Industrial
Hygiene Association.
*Cooper, W. C. 1973. Indicators of susceptibility of industrial chemicals. J. Occup. Med.
15:355–359.
Crouch, B., and Wilson, H. W. 1981. Calculating and comparing various acceptable levels of
risk. Risk Anal. 1:42–51.
Dallas, C. E., Theiss, J. C., Harrist, R. B., and Fairchild, E. J. 1985. Effect of subchronic
formaldehyde inhalation on minute volume and nasal deposition in Sprague-Dawl ey rats. J.
Toxicol. Environ. Health 16:553–564.
Dally, K. A., Hanrahan, L. P., and Woodbury, M. A. 1981. Formaldehyde exposure in nonoccu-
pational environments. Arch. Environ. Health 36:277–284.
*Day, J. J., Less, R. E. M., Clark, R. H., and Patter, P. L. 1984. Respiratory response to
formaldehyde and off-gas of urea formaldehyde foam insulation. Can. Med. Assoc. J.
131:1061–1065.
*Doull, J. 1991. The ACGIH TLVs: Past, present, and future. Appl. Occup. Environ. Hyg. 6:89–90.
*Dubreuil, A., Bouley, G., Godin, J., Boudine, C., and Girard, F. 1976. Inhalation, en contince,
de faibles doser de formal dehyde; et ude experimentale chez le rat. Eur. J. Toxicol.
9:245–250.
Edling, C., Odkwist, L., and Hellquist, H. 1985. Formaldehyde and the nasal mucosa. Br. J. Ind.
Med. 42:570–571.
Egle, J. L. 1972. Retention of inhaled formaldehyde, propionaldehyde, and acrolein in the dog.
Arch. Environ. Health 25:119–124.
*Elkins, H. B. 1950. Maximum allowable concentrations. In The chemistry of industrial toxicology,
pp. 214–236. New York: John Wiley and Sons.
Elkins, H. B. 1942. Maximal allowable concentrations. I. Carbon tetrachloride. J. Ind. Hyg. Toxicol.
24:233–235.
Ettinger, I., and Jeremias, M. 1955. A study of the health hazards involved in working with
flameproofed fabrics. NY State Dept. Labor Div. Ind. Hyg. Mon. Rev. 34:25–27.
Feinman, S. E. 1988. Formaldehyde sensitivity and toxicity. Boca Raton, FL: CRC Press.
*Frigas, E., Filley, W. V., and Reed, C. E. 1981. Asthma induced by dust from urea-formalde-
hyde foam insulating material. Chest 79:706–707.
*Gamble, J. F., McMichael, A. J., Williams, T., and Battigelli, M. 1976. Respiratory function and
symptoms: An environmental-epidemiological study of rubber workers exposed to a phenol-
formaldehyde type resin. Am. Ind. Hyg. Assoc. J. 37:499–513.
*Gammage, R. B., and Gupta, K. C. 1984. Formaldehyde. In Indoor air quality, eds. P. J. Walsh,
C. S. Dudney, and E. D. Copenhauer. Boca Raton, FL: CRC Press.
Garry, V. F., Oatman, L., Pleus, R., and Gray, D. 1980. Formaldehyde in the home; Some envi-
ronmental disease perspectives. Minn. Med. 2:107–111.
*Gibson, J. E. 1983. Formaldehyde toxicity. Washington, DC: Hemisphere.

Gough, M., et al. 1984. Report on the consensus workshop on formaldehyde. Environ. Health
Perspect. 58:324–380.
*Green, D. J., Sauder, L. R., Kulle, T. J., and Bascom, R. 1987. Acute response to 3.0 ppm
formaldehyde in exercisi ng healthy nonsmokers and asthmatics. Am. Rev. Respir. Dis.
135:1261–1266.
*Hanraha n, L. P., Dally, K. A., Anderson, H. A., Kanarek, M. S., and Rankin, J. 1984.
Formaldehyde vapor in mobile homes: Cross-sectional survey of concentrations and irritant
effects. Am. J. Public Health 74:1026–1027.
Hansen, J., and Olsen, J. H. 1995. Formaldehyde and cancer morbidity among male employees
in Denmark. Cancer Causes and Control 6(4):345–360.
*Harris, J. C., Rumack, B. H., and Aldrich, F. D. 1981. Toxicology of formaldehyde and
polyurethane foam insulation. J. Am. Med. Assoc. 245:243–246.
Heck, H. d’A. 1982. Biochemical toxicology of inhaled formaldehyde. CIIT Activities 2:3–7.
Heck, H. d’A. 1989. Toxicologic implications of formaldehyde formation in-vivo from industrial
chemicals and pharmaceuticals. CIIT Activities 9:1–5.
Heck, H. d’A., and Casanova, M. 1987. Isotopic effects and their implications for the covalent
binding of inhaled [3H] , and [14C] formaldehyde in rat nasal mucosa. Toxicol. Appl.
Heck, H. d’A., and Casanova-Schmitz, M. 1984. The relevance of disposition studies to the toxi-
cology of formaldehyde. CIIT Activities 4:1, 3–5.
Hendrick, D. J., and Lane, D. J. 1975. Formalin asthma in hospital staff. Br. Med. J. 1:607–608.
Hendrick, D. J., and Lane, D. J. 1977. Occupational formalin asthma. Br. J. Ind. Med. 34:11–18.
Hendrick, D. J., Rando, R. J., Lane, D. J., and Morris, M. J. 1982. Formaldehyde asthma:
Challenge exposure levels and fate after five years. J. Occup. Med. 24:893–897.
*Hickey, J. 1977. Pharmacokinetic Adjustments of TLV. PhD dissertation, University of North
Carolina, Raleigh.
*Holmstrom, M., Wilhelmsson, B., and Hellquist, H. 1989. Histological changes of the nasal
mucosa in rats after long-term exposure to formaldehyde and wood dust. Acta Otolaryngol.
108:274–283.
*Holness, D. L., and Nethercott, J. R. 1989. Health status for funeral service workers exposed to
formaldehyde. Arch. Environ. Health 44:222–228.
*Holness, D. L., O’Blenis, E. L., Pilger, C. W., Sass-Kortsak, A. M., and Nethercott, J. R. 1987.
Respiratory effects and dust exposures in hog confinement farming. Am. J. Ind. Med.
11:571–580.
*Holness, D. L., Purdam, J. T., and Nethercott, J. R. 1989. Acute and chronic respiratory effects
of occupational exposure to ammonia. Am. Ind. Hyg. Assoc. 50:646–650.
*Horvath, E. P., Anderson, H., Pierce, W. E., Hanrahan, L. P., and Wendlick, J. O. 1988. Effects
of formaldehyde on the mucous membranes and lungs: a study of an industrial population.
J. Am. Med. Assoc. 259:701–707.
*Hunter, D. 1987. Diseases of occupations, eds. P. A. B. Raffle, W. R. Lee, R. I. McCallum, and
R. Murry. Boston: Little, Brown.
Imbus, H. R., and Tochilin, S. J. 1988. Acute effect upon pulmonary function of low leve l
exposure to phenol-formaldehyde-resin-coasted wood. Am. Ind. Hyg. Assoc. J. 49:434–437.
*Ivanoff, N. 1911. On some aldehydes of practical importance (German). Arch. Hyg. 73:307–319.
*Kane, L. E., and Alarie, Y. 1977. Sensory irritation to formaldehyde and acrolein during single
and repeated exposures in mice. Am. Ind. Hyg. Assoc. J. 38:509–522.
*Kane, L. E., Barrow, C. S., and Alarie, Y. 1979. A short-term test to predict acceptabl e levels
of exposure to airborne sensory irritants. Am. Ind. Hyg. Assoc. J. 40:207–229.
Kauppinen, T. P., and Niemela, R. I. 1985. Occupational exposure to chemical agents in the
particleboard industry. Scand. J. Work Environ. Health 11:357–363.
Kerfoot, E. J., and Mooney, T. F. 1975. Formaldehyde and paraformaldehyde study in funeral
homes. Am. Ind. Hyg. Assoc. J. 36:533–537.

*Kerns, W. D., Pavkov, K. L., and Donofrio, D. J. 1983. Carcinogenicity of formaldehyde in rats
and mice after long-term inhalation exposure. Cancer Res. 43:4382–4392.
Kilburn, K. H., Seideman, B. C., and Warshaw, R. 1985. Neurobehavioral and respiratory symp-
toms of formaldehyde and xylene exposure in histology technicians. Arch. Environ. Health
40:229–233.
*Kilburn, K. H., Warshaw, R., and Thornton, J. C. 1989. Pulmonary function in histology techni-
cians compared with women from Michigan: Effects of chronic low dose formaldehyde on
a national sample of women. Br. J. Ind. Med. 46:468–472.
Krans, E. W. 1935. Effects of fumes during the moulding of certain types of plastics. Ind. Med.
Surg. 4:10–11.
*Kulle, T. J. 1993. Acute odor and irritation response in healthy nonsmokers with formaldehyde
exposure. Inhal. Toxicol. 5:323–332.
Kulle, T. J., and Cooper, G. P. 1975. Effects of formaldehyde and ozone on the trigeminal nasal
sensory system. Arch. Environ. Health 30:237–243.
*Kulle, T. J., Sauder, L. R., Hebel, J. R., Green, D. J., and Chatham, M. D. 1987. Formaldehyde
dose-response in healthy nonsmokers. J. Air. Pollut. Control Assoc. 37:919–924.
*LaNier, M. E. 1984. Threshold Limit Values: Discussion and 35 Year Index with Recommenda-
tions (TLVs 1946–81). Cincinnati, OH: American Conference of Governmental Industrial
Hygienists.
*Lee, H. K., Alarie, Y., and Karol, M. H. 1984. Indication of formaldehyde sensitivity in guinea
pigs. Toxicol. Appl. Pharmacol. 75:147–155.
Leung, H. W., and Paustenbach, D. J. 1988. Application of pharmacokinetics to derive biological
exposure indexes from threshold limit values. Am. Ind. Hyg. Assoc. J. 49:445–450.
*Levine, R. J. 1984. A brief review of the mortality experience of humans exposed to formalde-
hyde. CIIT Activities 4:1–4.
*Levine, R. J., DalCorso, D., Blunden, P. B., and Battigelli, M. C. 1984. The effects of occupational
exposure on the respiratory health of West Virginia morticians. J. Occup. Med. 26:91–98.
Liu, K. S., Huang, F. Y., Hayward, S. B., Wesdouski, J., and Sexton, K. 1991. Irritant effects of
formaldehyde exposure in mobile homes. Environ. Health Perspect. 94:91–94.
Main, D. M., and Hogan, T. J. 1991. Health effects of low-level exposure to formaldehyde. J.
Occup. Med. 25:896–900.
*Malaka, T., and Kodama, A. M. 1990. Respiratory health of plywood workers occupationally
exposed to formaldehyde. Arch. Environ. Health 45:288–294.
March, G. M. 1982. Proportional mortality patterns among chemical plant workers exposed to
formaldehyde. Br. J. Ind. Med. 39:313–322.
McLaughlin, J. K. 1994. Formaldehyde and cancer: a critical review. Inter. Arch. Occup. Environ.
Health 66:295–301.
Meyer, B. 1979. Urea formaldehyde resins. Reading, MA: Addison-Wesley.
Milbey, T. H., Key, M. M., Gibson, R. L., and Stokinger, H. E. 1964. Chemical hazards. In
Occupational diseases—A guide to their recognitions, Section VI. Washington, DC: U.S.
Department of Health, Education, and Welfare.
*Monticello, T. N., and Morgan, K. T. 1990. Correlation of cell proliferation and inflammation
with nasal tumors in F344 rats following chronic formaldehyde exposure. Proc Am. Assoc.
Cancer Res. 31:139.
*Monticello, T. N., Morgan, K. T., Everitt, J. I., and Popp, J. A. 1989. Effects of formaldehyde
gas on the respiratory tract of rhesus monkeys. Am. J. Pathol. 134:515–527.
*Monticello, T. M., Swenberg, J. A., Gross, E. A., Leininger, J. R., Kimbell, J. S., Seilkop, S.,
Starr, T. B., Gibson, J. E., and Morgan, K. T. 1996. Correlation of regional and nonlinear
formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res.
56:1012–1022.
Morgan, K. T. 1983. Localizat ion of areas of inhibition of nasal mucociliary function in rats fol-
lowing in vivo exposure to formaldehyde. Am. Rev. Respir. Dis. 127:166–172.

*Morgan, K. T., and Patterson, D. L. 1984. Frog palate mucociliary apparatus: Structure, function,
and response to formaldehyde gas. Fundam. Appl. Toxicol. 4:58–68.
Morgan, K. T., Patterson, D. L., and Gross, E. A. 1983. Formaldehyde and the nasal mucociliary
apparatus. In Toxicology, epidemiology, mechanisms, eds. J. J. Clary, J. E. Gibson, and R. S.
Waritz, pp. 193–199. New York: Marcel Dekker .
Morgan, K. T., and Patterson, D. L. 1986. Responses of the nasal muciliary apparatus of F-344
rats to formaldehyde gas. Toxicol. Appl. Pharmacol. 82:1–13.
*Morgan, K. T., Jiang, X. Z., Starr, T. B., and Kerns, W. D. 1986. More precise localization of
nasal tumors associated with chronic exposure of F344 rats to formaldehyde gas. Toxicol.
Appl. Pharmacol. 82:264–271.
Nagornyi, P. A. Sudakora, Z. H. A., and Shchablenko, S. M. 1979. General toxic and allergic
effects of formaldehyde. Gig. Trud. Prof. Zabol. 1:27–30.
National Aeronautics and Space Administration. 1991. Spacecraft Maximum Allowable Concentra-
tions for Formaldehyde. Houston, TX: Johnson Space Center.
National Institute of Occupational Safety and Health. 1973. The industrial environment—Its evalua-
tion and control. Washington, DC: U.S. Department of Health, Education, and Welfare.
*National Institute of Occupational Safety and Health. 1976. Criteria for a Recommended
Standard. Occupational Exposure to Formaldehyde. Washington, DC: U.S. Department of
Health, Education, and Welfare.
National Institute of Occupational Safety and Health. 1981. Formaldehyde: Evidence of Carcino-
genicity. Current Intelligence Bulletin 34. Washington, DC: U.S. Department of Health and
Human Services.
*National Research Council. 1980. Formaldehyde: An assessment of its health effects. Washington,
DC: National Academy of Sciences.
*National Research Council. 1981. Formaldehyde and other aldehydes. Washington, DC: National
Academy of Sciences.
Nethercott, J. R., and Holness, D. L. 1988. Health status of a group of sewage treatment workers
in Toronto, Canada. Am. Ind. Hyg. Assoc. J. 49:346–350.
Nethercott, J. R., Holness, D. L., Rotham, N., and O’Toole, T. 1990. Health problems in metal
workers exposed to a coolant oil containing Kathon 886 MW. Am. J. Contact Derm. 1:1–16.
*Nielsen, G. D. 1991. Mechanisms of activation of the sensory irritant receptor by airborne
chemicals. Crit. Rev. Toxicol. 21:183–208.
*Nielsen, G. D., and Alarie, Y. 1982. Sensory irritation, pulmonary irritation, and respiratory stim-
ulation by airborne benzene and alkylbenzenes: Prediction of safe industrial exposure levels
and correlation with their thermodynamic properties. Toxicol. Appl. Pharmacol. 65:459–477.
*Nordman, H., Keskinen, H., and Tuppurainen, M. 1985. Formaldehyde asthma—Rare or over-
looked? J. Allergy Clin. Immunol. 75:91–95.
Norman, G. R., Pengelly, L. D., Kerigan, A. T., and Goldsmith, C. H. 1986. Respiratory function
of children in homes insulated with urea formaldehyde foam insulation. Can. Med. Assoc. J.
134:1135–1137.
*Nunn, A. J., Craigen, A. A., Darbyshire, J. H., Venables, K. M., and Newman-Taylor, A. J.
1990. Six year follow up of lung function in men occupationally exposed to formaldehyde.
Br. J. Ind. Med. 47:747–752.
*Occupational Safety and Health Administration. 1985. Occupational exposure to formaldehyde.
Proposed rule and notice of hearing. 29 CFR 1910. Fed. Reg. 50:50412.
Occupational Safety and Health Administration. 1989. Air contaminants: Final rule 29 CFR 1910.
Fed. Reg. 54:2332–2960.
*Olsen, J. H., and Dossing, M. 1982. Formaldehyde induced symptoms in day care centers. Am.
Ind. Hyg. Assoc. J. 43:366–370.
*Omenn, G. S. 1982. Predictive identification of hypersusceptible individuals. J. Occup. Med.
24:369–374.
Paustenbach, D. J. 1990a. Occupational exposure limits: their critical role in preventive medicine
and risk management—A guest editorial. Am. Ind. Hyg. Assoc. J. 51:A332–A336.

Paustenbach, D. J. 1990b. Health risk assessment and the practice of industrial hygiene. Am. Ind.
Hyg. Assoc. J. 51:339–351.
*Paustenbach, D. J. 1994. Occupational exposure limits, pharmacokinetics, and unusual work
schedules. In Patty’s industrial hygiene and toxicology, 3rd ed., vol. 3A, The work environment,
eds. L. Cralley, L. Cralley, and R. Harris, pp. 191–348. New York: John Wiley and Son.
Paustenbach, D. J., and Langner, R. R. 1986. Corporate occupational exposure limits: The current
state of affairs. Am. Ind. Hyg. Assoc. J. 47:809–818.
Popa, V., Teculescu, D., Stanescu, D., and Gavrilescu, N. 1969. Bronchial asthma and asthmatic
bronchitis determined by simple chemicals. Chest 56:395–404.
Preuss, P. W., Dailey , R. L., and Lehman, E. S. 1985. Exposure to formaldehyde. In
Formaldehyde: Analytical chemical and toxicology, vol. 2, ed. V. Turoski, pp. 247–259.
Washington, DC: American Chemical Society.
Rathery, F., Piedelieure, R., and Delarue, J. 1940. Death by absorption of formalin. Ann. Med.
Leg. Crimiru. Police Sci. 20:201–209.
Reitz, R. H., Schumann, A. M., Watanabe, P. G., Quast, T. F., and Gehring, P. J. 1979.
Experimental approach for evaluating genetic and epigenetic contributions to chemical car-
cinogenesis. Proc. Am. Assoc. Cancer Res. 20:266–281.
Report on the Consensus Workshop on Formaldehyde. 1984. Environ. Health Perspect. 58:323–
381.
*Ritchie, I. N., and Lehnen, R. G. 1987. Formaldehyde-related health complaints of residents liv-
ing in mobile and conventional homes. Am. J. Public Health 77:323–328.
Roach, S. A., and Rappaport, S. M. 1990. But they are not threshold: A critical analysis of the
documentation of the threshold limit values. Am. J. Ind. Med. 17:727–753.
Robinson, J. C., Paxman, D. G., and Rappaport, S. M. 1991. Implications of OSHA’s reliance on
TLVs in developing the Air Contaminants Standard. Am. J. Ind. Med. 19:3–13.
Rodricks, J., Brett, S., and Wrenn, G. 1987. Significant risk decisions in federal regulatory agen-
cies. Regul. Toxicol. Pharmacol. 7:307–320.
Roush, G. C., Walath, J., Stayner, L. T., Kaplan, S. A., Flannery, J. T., and Blair, A. 1987.
Nasopharyngeal cancer, sinonasal cancer, and occupational cancer related to formaldehyde:
A case control study. J. Natl. Cancer Inst. 9:1221–1224.
*Rusch, G. M., Clary, J. J., Rinehart, W. E., and Bolte, H. F. 1983. A 26-week inhalation toxicity
study with formaldehyde in the monkey, rat, and hamster. Toxicol. Appl. Pharmacol.
68:329–343.
Ruth, J. H. 1986. Odor thresholds and irritation levels of several chemical substances: A review.
Am. Ind. Hyg. Assoc. J. 47:142–151.
Salem, H., and Cullibine, H. 1960. Inhalation toxicities of some aldehydes. Toxicol. Appl.
Sardinas, A. V., Most, R. S., Guilietti, M. A., and Honchar, P. 1979. Health effects associated
with urea-formaldehyde foam insulation in Connecticut. J. Environ. Health 41:270–272.
Sass-Kortsak, A. M., Holness, D. L., Pilger, C. W., and Nethercott, J. R. 1986. Wood dust and
formaldehyde exposures in the cabinet-making industry. Am. Ind. Hyg. Assoc. J. 47:747–753.
*Sauder, L. R., Chathman, M. D., Green, D. J., and Kulle, T. J. 1986. Acute pulmonary
response to formaldehyde exposure in healthy subjects. J. Occup. Med. 28:420–424.
*Sauder, L. R., Green, D. J., Chatham, M. D., and Kulle, J. T. 1987. Acute pulmonary response
of asthmatics to 3.0 ppm formaldehyde. Toxicol. Ind. Health 3:569–578.
*Schachter, E. N., Witek, T. J. Brody, D. J., Tosun, T., Beck, G. J., and Leaderer, B. P. 1986.
A study of respiratory effects from exposure to 2 ppm formaldehyde in healthy subjects.
*Schacht er, E. N., Witek, T. J., Tosun, T., and Beck, G. J. 1987. A study of respiratory effects
from exposure to 2.0 ppm formaldehyde in occupationally exposed workers. Environ. Res.
44:188–205.
*Schaper, M. 1993. Development of a database for sensory irritants and its use in establishing
occupational exposure limits. Am. Ind. Hyg. Assoc. J. 54:488–504.

*Schoenberg, J. B., and Mitchell, C. A. 1975. Airway disease caused by phenolic (phenol-
formaldehyde) resin exposure. Arch. Environ. Health 30:574–577.
*Schuck, E. A., Stephens, E. R., and Middleton, J. T. 1966. Eye irritation response at low con-
centrations of irritants. Arch. Environ. Health 13:570–575.
Sheppard, D., Eschenbacher, W. L., and Epstein, J. 1984. Lack of bronchomotor response to up
to 3 ppm formaldehyde in subjects with asthma. Environ. Res. 35:133–139.
*Shipkovitz, H. D. 1968. Formaldehyde Vapor Emissions in the Permanent-Press Fabrics Industry.
In-house report TR-52. September. Cincinnati, OH: Occupational Health Program, U.S. Public
Health Service.
*Shusterman, D. 1992. Critical review: The health significance of environmental odor pollution.
Shusterman, D. J., and Dager, S. R. 1991. Prevention of psychological disability after occupational
respiratory exposures. Occup. Med. 6:11–27.
Shusterman, D., Balmes, J., and Cone, J. 1988. Behavioral sensitization to irritants/odorants after
acute overexposures. J. Occup. Med. 30:565–567.
*Shusterman, D., Lipscomb, J., Neutra, R., and Satin, K. 1991. Symptom prevalence and odor-
worry interaction near hazardous waste sites. Environ. Health Perspect. 94:25–30.
Smith, K. A., Williams, P. L., Middendorf, P. J., and Zakraysek, N. 1984. Kidney dialysis: ambi-
ent formaldehyde levels. Am. Ind. Hyg. Assoc. J. 45:48–50.
*Smythe, H. F. 1956. Improved communication: Hygienic standard for daily inhalation. Am. Ind.
Hyg. Assoc. Q. 17:129–185.
Sparks, P. J., and Peters, L. M. 1980. Respiratory morbidity in workers exposed to dust contain-
ing phenolic resin. Int. Arch. Occup. Environ. Health 45:221–229.
Spirtas, R., Steinberg, M., Wands, R. C., and Weisburger, E. K. 1981. Identification and classifi-
cation of carinogens: Procedures of the Chemical Substances Threshold Limit Value
Committee, ACGIH. Am. J. Public Health 76:1232–1235.
*Starr, T. B. 1990. Quantitative risk estimation for formaldehyde. Risk Anal. 10:85–91.
Starr, T. B. 1986. Testimony before OSHA on proposed formaldehyde rules. CIIT Activities 6:3–4.
*Starr, T. B., and Buck, R. D. 1984. The importance of delivered dose in estimating low dose
cancer risk from inhalation exposure to formaldehyde. Fundam. Appl. Toxicol. 4:740–753.
Starr, T. B., and Gibson, J. E. 1985. The mechanistic toxicology of formaldehyde and its impli-
cations for quantitative risk assessment. Annu. Rev. Pharmacol. Toxicol. 25:745–767.
Stokinger, H. E. 1970. Criteria and procedures for assessing the toxic responses to industrial
chemicals. In Permissible levels of toxic substances in the working environment. Geneva: ILO.
Stokinger, H. E. 1977. The case for carcinogen TLV’s continues strong. Occup. Health Safety
46:54–58.
*Stokinger, H. E. 1981. Threshold limit values: Part I. In Dangerous properties of industrial materials
report, pp. 8–13.
Stott, W. T., Reitz, R. H., Schumann, A. M., and Watanabe, P. G. 1981. Genetic and nongenetic
events in neoplasia. Food Cosmet. Toxicol. 19:567–576.
Swenberg, J. A., Kerns, W. D., Mitchell, R. E. Gralla, E. J., and Pavkov, K. C. 1980. Induction
of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde
vapor. Cancer Res. 30:3398–3402.
Swenberg, J. A., Barrow, C., and Boreicko, C. 1983. Nonlinear biological responses to formalde-
hyde and their implications for carcinogenic risk assessment. Carcinogenesis 4:945–952.
Taraschuk, I. G., Holness, D. L., and Nethercott, J. R. 1989. Health status of copper refinery
workers with specific reference to selenium exposure. Arch. Environ. Health 44:291–297.
Thrasher, J. D., Wojdani, A., Cheung, G., and Heusen, G. 1987. Evidence for formaldehyde anti-
bodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes.
Thun, M. J., Lakat, M. F., and Altman, R. 1982. Symptom survey of residents of homes insulated
with urea-formaldehyde foam. Environ. Res. 29:320–334.

Tobe, M., Kaneko, T., Uchida, Y., et al. 1985. Studies of the inhalation toxicity of formalde-
hyde, pp. 1–94. National Sanitary and Medical Laboratory Service, Department of the
Organism Safety Research Center, Japan: U.S. Environmental Protection Agency English trans-
lation report TR-85-0236. Washington, DC: U.S. EPA.
*Uba, G., Pachorek, D., Bernstein, J., Garabrant, D. H., Balmes, J. R., Wright, W. E., and Amar,
R. B. 1989. Prospective study of respiratory effects of formaldehyde among healthy and
asthmatic medical students. Am. J. Ind. Med. 15:91–101.
Uehara, M. 1978. Follicular contact dermatitis due to formaldehyde. Dermatologica 156:48–54.
U.S. Environmental Protection Agency. 1990. Reducing risk. Washington, DC: EPA Science
Advisory Board.
Watanabe, P. G., Young, J. D., and Gehring, P. J. 1977. The importance of non-linear (dose-
dependent) pharmacokinetics in hazard assessment. J. Environ. Pathol. Toxicol. 1:147–159.
*Weber-Tschopp, A., Fischer, T., and Grandjean, E. 1977. Irritating effects of formaldehyde in
humans. Int. Arch. Occup. Environ. Health 39:207–218.
Williams, T. M., Levine, R. J., and Blunden, P. B. 1984. Exposure to embalmers to formalde-
hyde and other chemicals. Am. Ind. Hyg. Assoc. J. 45:172–176.
Wilmer, J. W., Woutersen, R. A., Appelman, L. M., Leeman, W. R., and Feron, V. J. 1989.
Subchronic (13-week) inhalation toxicity study of formaldehyde in male rats: 8-Hour intermit-
tent versus 8-hour continuous exposure. Toxicol. Lett. 47:287–293.
*Witek, T. J., Schachter, E. N., Tosun, T., Beck, G. J., and Leaderer, B. P. 1987. An evaluation
of respiratory effects following exposure to 2.0 ppm formaldehyde in asthmatics: Lung func-
tion, symptoms, and airway reactivity. Arch. Environ. Health 42:230–237.
*World Health Organization. 1977. Methods Used in Establishing Permissible Levels in
Occupational Exposure to Harmful Agents. Technical report 601. Geneva: International Labor
Office, WHO.
*World Health Organization. 1989. Formaldehyde. Environmental Health Criteria 89. Geneva:
International Labor Office.
Woutersen, R. A., Van Garderen-Hoctmer, A., Bruijntjes, J. P., Zwart, A., and Feron, J. 1988.
Nasal tumors in rats after severe injury to the nasal mucosa and prolonged exposure to 10
ppm formaldehyde. J. Appl. Toxicol. 91:39–46.
Zannini, D., and Russo, L. 1957. Consequences of acute intoxicants due to gaseous irritants of
the respiratory system. Lav. Um. 9:241–253.
*Zielhuis, R. L. 1974. Permissible limits for occupational exposure to toxic agents: A discussion
on differences in approach between US and USSR. Int. Arch. Arbeitsmed. 33:212–286.
Ziem, G. E., and Castleman, B. I. 1989. Threshold limit values: Historical perspectives and cur-
rent practice. J. Occup. Med. 13:910–918.
*Zurlo, N. 1983. Formaldehyde and derivatives. In Encyclopedia of occupational health and safety,
ed. L. Parmeggiani, 3rd ed., pp. 914–916. Geneva: International Labor Office.
Copyright of Journal of Toxicology & Environmental Health is the property of Taylor & Francis Ltd and its
content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for individual use.

Ni Hms 636912

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Ni Hms 636912

Uploaded by

Copyright:

Available Formats

A RECOMMENDED OCCUPATIONAL EXPOSURE LIMIT

FOR FORMALDEHYDE BASED ON IRRITATION

Journal of Toxicology and Environmental Health, 50:217–263, 1997

Over the past 40 yr, many organizations in numerous countries

often impossible to achieve because of either engineering or economic

fiberboard, and particle board (NIOSH, 1976; Gibson, 1983). Other

developing OELs has generally been shown to be acceptable even by

TABLE 1. Worldwide occupational exposure limits (OEL) for formaldehyde in 1994

Country/agency OEL (ppm) Type of guideline

NIOSH 0.1 C (15 min)

1946–1947 10 MAC-TWA Prevent skin and mucous membrane irritation

Acute Studies (Animals)

The panel considered these data useful for deciding whether a CV or

Seventy-four human studies were identified and 52 were considered

absence of interferences are quite satisfactory. In short, one has to

was observed in 39% of the volunteers at 0 ppm, 42% at 0.35 ppm,

applicable only for setting a STEL or CV due to the extremely short

more at risk of suffering from formaldehyde-related irritation or asthma

TABLE 3. Concentration-response information for formaldehyde obtained from irritation studies

Study Response Concentration Duration

Note. *A mobile home study; NA, not available.

The panel considered these studies to be among the most important,

ate exercise. The purpose of this study was to determine if exposure

throat irritation occurred at 0 ppm and, consistent with the results

formaldehyde (as was erroneously concluded by the authors from

observed. The panel concluded that the information provided in the

study of the carpentry shop worker study they performed in 1982.

Holness and Nethercott (1989) compared 84 funeral service workers

an incidence of irritation less than that usually reported in unexposed

taining particle board in producing irritation. The mean formaldehyde

of irritation and typical workplace concentrations of formaldehyde.

higher levels of formaldehyde than the older homes. Irritation was

the technicians who were typically exposed to higher concentrations of

compare the incidence of irritation. The purpose was to determine if

10 ppm. At concentrations above 10 ppm, there is at least a seven-

suggested that asthmatics respond to formaldehyde like nonasthmatics.

tors, the background incidence of eye irritation, self-selection bias, or

 At 3.0 ppm, in environmental chamber studies, Kulle et al. (1987)

underestimated the actual concentration of formaldehyde. In addition,

that irritation is a threshold- and time-independent response since expo-

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

*Citation not discussed in text.

You might also like

At 3.0 ppm, in environmental chamber studies, Kulle et al. (1987)