See

discussions, stats, and author profiles for this publication at:

https://www.researchgate.net/publication/51820816

Exposure to Formaldehyde and Its

Potential Human Health Hazards

Article in Journal of Environmental Science and Health Part C Environmental

Carcinogenesis & Ecotoxicology Reviews · November 2011
DOI: 10.1080/10590501.2011.629972 · Source: PubMed

CITATIONS READS

38 248

3 authors, including:

Ki-Hyun Kim Jong-Tae Lee

Hanyang University Korea University
619 PUBLICATIONS 8,461 CITATIONS 91 PUBLICATIONS 6,139 CITATIONS

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Plant specific emission pattern of biogenic volatile organic compunds (BVOCs)

View project

Studies on utilization of nanoparticles for removal and sensing of heavy metals.

View project

All content following this page was uploaded by Ki-Hyun Kim on 11 May 2014.

The user has requested enhancement of the downloaded file.

This article was downloaded by: [Ki-Hyun Kim]
On: 22 November 2011, At: 12:57
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Journal of Environmental Science and

Health, Part C
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lesc20

Exposure to Formaldehyde and Its

Potential Human Health Hazards
a b b
Ki-Hyun Kim , Shamin Ara Jahan & Jong-Tae Lee
a
Department of Environment & Energy, Sejong University, Seoul,
Korea
b
Department of Environmental Health, Korea University, Seoul,
Korea

Available online: 22 Nov 2011

To cite this article: Ki-Hyun Kim, Shamin Ara Jahan & Jong-Tae Lee (2011): Exposure to Formaldehyde
and Its Potential Human Health Hazards, Journal of Environmental Science and Health, Part C, 29:4,
277-299

To link to this article: http://dx.doi.org/10.1080/10590501.2011.629972

PLEASE SCROLL DOWN FOR ARTICLE

Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions

This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.
 Journal of Environmental Science and Health, Part C, 29:277–299, 2011
Copyright
C Taylor & Francis Group, LLC
ISSN: 1059-0501 print / 1532-4095 online
DOI: 10.1080/10590501.2011.629972

Exposure to Formaldehyde
and Its Potential Human
Health Hazards
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

Ki-Hyun Kim,1 Shamin Ara Jahan,2 and Jong-Tae Lee2

1
Department of Environment & Energy, Sejong University, Seoul, Korea
2
Department of Environmental Health, Korea University, Seoul, Korea
A widely used chemical, formaldehyde is normally present in both indoor and outdoor
air. The rapid growth of formaldehyde-related industries in the past two decades re-
flects the result of its increased use in building materials and other commercial sectors.
Consequently, formaldehyde is encountered almost every day from large segments of so-
ciety due to its various sources. Many governments and agencies around the world have
thus issued a series of standards to regulate its exposure in homes, office buildings,
workshops, public places, and food. In light of the deleterious properties of formalde-
hyde, this article provides an overview of its market, regulation standards, and human
health effects.

Keywords: formaldehyde; health effects; exposure levels; regulatory guideline

1. INTRODUCTION
Formaldehyde (HCHO) is an important chemical, widely used not only in
construction (wood processing, furniture, textiles, and carpeting) but also in
various industries [1, 2]. It is also a byproduct of certain natural (e.g., for-
est fires) and anthropogenic activities (e.g., smoking tobacco, burning auto-
motive (and other) fuels, and residential wood burning) [1]. Formaldehyde is
even a component of many consumable household products such as antiseptics,
medicines, cosmetics, dish-washing liquids, fabric softeners, shoe-care agents,
carpet cleaners, glues and adhesives, lacquers, etc. [3, 4]. Its application is ex-
tended further to food preservatives such as some Italian cheeses, dried foods,
and fish [5, 6]. Because of the widespread use of formaldehyde-containing prod-
ucts, it is generally found more abundantly indoors than outdoors. Acute expo-
sure to formaldehyde can, however, cause various health-related issues such
as irritation on various body parts (eyes, nose, throat, and skin). Moreover,

Address correspondence to K.-H. Kim, Department of Environment & Energy, Sejong

University, Seoul 143-747, Korea. E-mail: khkim@sejong.ac.kr
277
 278 K.-H. Kim, S. A. Jahan, and J.-T. Lee

sustained exposure can lead to certain types of cancers (e.g., nasopharyngeal)

and asthma [1, 7–9].
As the world’s formaldehyde industry grows to meet the demands of eco-
nomic expansion, its pollution is perceived to affect millions of people. Due to
growing concern over its deleterious effects, many nations (i.e., Denmark, Swe-
den, the Netherlands, Italy, Finland, Germany, Canada, United States, etc.)
have already adopted or proposed stringent regulations on its concentration
levels (e.g., indoor air quality standards for formaldehyde to limit exposures)
[10]. The primary objective of this review is to summarize the current findings
of its pollution status and the associated health impacts that can arise from its
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

exposure.

2. THE STATUS OF FORMALDEHYDE POLLUTION

AND ITS EXPOSURE ROUTE
Formaldehyde is normally present in both indoor and outdoor air due to its
abundant and (almost) ubiquitous sources. Given its economic importance and
widespread use, many people are exposed to formaldehyde during occupational
activities. This involves not only individuals employed in the direct manu-
facture of products containing certain levels of formaldehyde but also those
actively utilizing such products (e.g., construction and decoration). Exposure
occurs primarily by inhaling formaldehyde gas (or vapor) from the air or by ab-
sorbing liquids containing formaldehyde through the skin. Hence, those work-
ing in certain job sectors (e.g., manufacturers of resins, plywood, and particle
board; laboratory technicians; certain health care professionals; fire fighters;
and mortuary employees) are exposed to high doses of formaldehyde relative to
the general public. Table 1 presents the range of formaldehyde concentration
to which workers are commonly exposed under various conditions.
The highest levels of airborne formaldehyde have been detected in indoor
air. According to the Air Pollution Exposure of Adult Urban Populations in
Europe (EXPOLIS) study conducted in Helsinki, Finland in 1997, the mean
formaldehyde values of personal exposure, indoor residential areas, outdoor
residential areas, and workplaces were 21.4, 33.3, 2.60, and 12.0 parts per
billion (ppb), respectively [11]. Although formaldehyde can be released from
various indoor sources, many construction materials (e.g., medium-density
fiber board, particleboard, and plywood), which contain phenol–formaldehyde
or urea–formaldehyde resin glues, and glass wool insulation (with similar
types of binders) are known to emit large quantities of formaldehyde [12].
Formaldehyde can also result from gas-phase ozonolysis of indoor alkenes
(often monoterpenes), which occur in numerous household products (e.g.,
air fresheners, fragrances products, etc.) [13, 14]. Electronic equipments
such as photocopiers and laser printers are also reported to release certain
quantities of formaldehyde [15]. The level of its emission from the indoor
 Human Health Hazards of Formaldehyde 279
Table 1: Selected Case Studies of Formaldehyde Exposure Levels for the Workers of
Various Professions

Exposure range Study

Profession (ppm) location Reference

Chemical workers 0.04 to 0.4 Turin, Italy [144]

Furniture workers 0.16 to 0.4 Copenhagen, [145]
Denmark
Plywood, particle board 0.28 to 3.48 Hawaii, USA [146]
production workers
Office workers 0.07 to 0.13 Tainan, Taiwan [147]
Laboratory technicians 0.11 to 0.27 Ankara, Turkey [148]
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

Electrician/mechanic 0.06 to .18 Massachusetts, [149]

USA
Cleaner 0.15 to 0.21 Denver, USA [150]
Firefighter 0.10 to 2.2 Arizona, USA [151]
Mortuary employees 0.5 to 1.5 Utah, USA [152]

sources can be affected by such factors as area of exposed boards, temperature,

relative humidity, frequency of ventilation, etc. [16]. As formaldehyde emission
can proceed via evaporation (methylene glycol) or initial hydrolysis, its diffu-
sion processes are likely to exert a direct influence on its emission strengths
[17]. Some examples of its release rates per unit surface area (µg m−2 hr−1) are
listed for a number of consumer products in Table 2.
Note that the level of exposure to formaldehyde is typically lower in com-
mon indoor places relative to occupational conditions. Hence, a great number
of people are routinely exposed to low levels of formaldehyde in their daily lives
[6]. The average outdoor concentrations reported in urban areas of the United
States were in the range of 11 to 20 ppb [18]. IARC [19] generalized that its
outdoor concentrations in urban environments ranged from 0.08 to 16.3 ppb,

Table 2: Release Rates of Formaldehyde Per Unit Surface Area (µg m−2 hr−1) from
Consumer Products

Emission rate Study

Products (µg m-2 hr-1) location Reference

Bare urea–formaldehyde 9 to 1578 Gdynia, Poland [153]

wood products
Coated urea−formaldehyde 1 to 461 Gdynia, Poland [153]
wood products
Permanent press fabrics 42 to 214 Seoul, South Korea [154]
Decorative laminates 4 to 50 Seoul, South Korea [154]
Fiber glass products 16 to 32 Seoul, South Korea [154]
Paper grocery bags and 0.5 to 0.6 California, USA [155]
towels
Latex paint 326 to 854 California, USA [155]
Nail polish 20 to 700 California, USA [155]
 280 K.-H. Kim, S. A. Jahan, and J.-T. Lee

depending on local conditions. Its sources of outdoor environment are also di-
verse enough to include (1) power plants, manufacturing facilities, (2) inciner-
ators, (3) automobile engines, and (4) the burning of forests and manufactured
wood products [20–22].

3. USE AND PRODUCTION INVENTORY OF FORMALDEHYDE

Formaldehyde is one of the most commercially important aldehydes. It is used
most extensively in the production of resins with urea, phenol and melamine,
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

and polyacetal resins [23]. Formaldehyde-based resins are also used as adhe-
sives and impregnating resins in the manufacture of particle-board, plywood,
furniture, and other wood products [24]. They are also used in the textile,
leather, rubber, and cement industries [19]. Further uses include binders for
foundry sand, stone wool, and glass wool mats in insulating materials, abra-
sive paper, brake linings, dyes, tanning agents, precursors of dispersion and
plastics, extraction agents, crop protection agents, animal feeds, perfumes,
vitamins, flavorings, and drugs [19, 23, 25, 26]. Formaldehyde is also used as
an antimicrobial agent in many cosmetics products, including soaps, sham-
poos, hair preparations, deodorants, lotions, make-up, mouthwashes, and nail
products [23].
As the global consumption of formaldehyde mainly occurs in the form of
construction/remodeling activity, vehicle and furniture production, and origi-
nal equipment manufacture (OEM), its market demand can be influenced by
general economic conditions to a degree. For instance, annual production of
formaldehyde in the United States recorded about 1 million metric tons (0.9
million tons) in 1960 and underwent 5-fold increases by 2006 [27]. As of 2009,
the amount reached 21 million metric tons [28]. This kind of situation is not
much different in other countries. For instance, the production and consump-
tion of formaldehyde was 580,000 tons in Korea in 2000, and its demand is
increasing every year [29]. The production of formaldehyde-based resins in
Korea was about 207,000 tons in 2005, which was equivalent to 39% of the to-
tal adhesive production. Moreover, a dominant proportion (e.g., 75% or 155,000
tons) of formaldehyde-based resin adhesives is represented by those produced
in the form of UF resin adhesives [30].
World consumption of formaldehyde is forecasted to grow at an average
annual rate of 4% from 2009 through 2014 as a result of increased pro-
duction of wood panels, laminates, pentaerythritol, etc. [28]. Internationally,
152 formaldehyde suppliers in 25 countries, 59 paraformaldehyde suppliers
in 15 countries, and 21 trioxane suppliers in 9 countries were identified in
2009 [31–33]. Because of issues associated with transportation and storage of
formaldehyde, its production is generally made very near the site of final con-
sumption. Therefore, its international trade is considerably low, accounting for
less than 2% of worldwide production [27].
 Human Health Hazards of Formaldehyde 281

4. EFFECTS OF FORMALDEHYDE ON HEALTH

An extensive body of literature exists on both the acute and chronic health ef-
fects of formaldehyde exposure. Formaldehyde released from external sources
enters the human body either via inhalation of its gaseous form or via inges-
tion of substances [1, 19, 34, 35]. There is also some possibility of intake via
dermal absorption [34]. Once absorbed, almost every tissue in the body has the
ability to break down formaldehyde [36]. It is usually converted to a nontoxic
chemical called formate, which is excreted through the urine [35] and can be
exhaled via conversion to carbon dioxide. It can also be broken down so that
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

the body can use it to make larger molecules needed in human tissues. Other-
wise, it can be attached to deoxyribonucleic acid (DNA) or to protein in body
[35]. A summary of the acute and chronic health effects due to formaldehyde
transmission is provided next.

4.1. Effects Due to Acute Exposure

Formaldehyde is known to induce acute poisoning and cause irritation, as
well as other immunotoxic effects. It is a highly reactive chemical that readily
reacts with biological tissues, particularly the mucous tissues lining the respi-
ratory tract and the eyes [35]. Mucous tissues are moist and characterized by
a thin-walled cellular (epithelial) layer that is highly susceptible to chemical
irritation [20]. As a result of its reactivity, inhaled formaldehyde is rapidly and
almost entirely absorbed by the mucous tissues lining the upper-respiratory
tract. Hence, if supplied at low or medium concentrations, it cannot penetrate
farther than the major bronchi of the respiratory tract [34].

4.1.1. Irritation
Acute mucus membrane irritation is the most common adverse effect of
formaldehyde exposure, often leading to dry skin, dermatitis, tearing eyes,
sneezing, and coughing [37]. Serious formaldehyde exposure can often re-
sult in eye conjunctivitis and nasal and pharyngeal diseases, while increasing
the likelihood of dangerous conditions such as laryngospasm and pulmonary
edema [38–41]. In a study conducted in China, 66 workers in the chemical in-
dustry exposed occupationally to formaldehyde were reported to suffer from
congestion in the cornea, nasal membrane, and pharynx [42]. In other stud-
ies, volunteers exposed to formaldehyde in the range of 0.25 to 3.0 ppm ex-
perienced eye, nose, and throat irritation [37]. Kulle [37] reported that eye
irritation was the dominant symptom with a linear trend at a dose range of
0.5–3 ppm. Although no effect was observed below 0.5 ppm, 21% experienced
mild eye irritation at 1 ppm. One Finish study reported that formaldehyde can
cause sensory irritation more effectively than the mixture of common volatile
organic compounds (VOCs) [43].
 282 K.-H. Kim, S. A. Jahan, and J.-T. Lee

4.1.2. Acute Poisoning

Acute formaldehyde poisoning can result from inhaling its fumes or from
swallowing its liquid phase. The severity of its poisoning depends on the
inhaled (or ingested) amount. Acute ingestion of formaldehyde will lead to
(1) irritation and burns of the mouth and throat, (2) burns and ulceration of
the gastrointestinal tract, (3) chest or abdominal pain, (4) nausea, (5) vomiting,
(6) diarrhea, and (7) gastrointestinal hemorrhage [44–45]. Formaldehyde in-
gestion may also result in metabolic acidosis, tachypnoea, jaundice, protein-
uria, haematuria, and acute renal failure [45]. A total of 17 employees in
a pharmaceutical company who continuously inhaled formaldehyde vapors
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

showed symptoms of irritated eyes, tearing, sneezing, coughing, chest conges-

tion, fever, heartburn, lethargy, and loss of appetite [46]. As a result of this
poisoning, some even experienced vomiting, abdominal pain, and nodal tachy-
cardia [46]. In another study, it was found that an adult experienced abdominal
pain, bloody stools, hematemesis, and a high serum alanine-amino transferase
(ALT) after imbibing formaldehyde contaminated water [47]. It was also re-
ported that symptoms of nausea, vomiting, and dizziness can be found after
eating formaldehyde preserved fish [48, 49].

4.1.3. Dermal Allergies

Skin sensitization following dermal exposure to formaldehyde has been
well documented [50]. Human skin sensitivity to formaldehyde has been asso-
ciated with many situations of dermal exposure, including contact with forma-
lin, formaldehyde-containing resins, formaldehyde-treated fabrics, formalde-
hyde containing household products, facial tissues, etc. [51–54]. Formaldehyde
has been widely reported to cause dermal allergic reactions in occupation-
ally exposed nurses, doctors, and dentists, as well as cosmetic workers, textile
workers, and construction workers [54–56].
Four of 10 operators of chemical melting devices in a phenol-formaldehyde
factory experienced dermatitis after occupational contact with formaldehyde
[57]. In another instance, at a mushroom farm where formaldehyde was
sprayed to make the products whiter, two-thirds of the employees exposed at
0.49–3 ppm range experienced dermatitis on their arms and forearms [58]. The
symptoms of these employees included red spots, swelling, irritation, pain, and
burning sensations.

4.1.4. Allergic Asthma

Asthma induced by inhaled formaldehyde may be classified as an irritant-
induced asthma, as short exposures to high level formaldehyde are identified to
cause a sudden onset of asthmatic symptoms called “Reactive airways dysfunc-
tion syndrome” (RADS) [59, 60]. Because of its airway-irritating properties, it
may also aggravate preexisting asthma [60]. It was reported that the likelihood
 Human Health Hazards of Formaldehyde 283
for the development of allergic asthma increases proportionately with level of
indoor formaldehyde concentration, especially when levels exceed 0.08 ppm
[61]. An Australian study also found that indoor formaldehyde levels, when ex-
ceeding 0.09 ppm, significantly increased likelihood of asthma in children [62].
A study conducted in France found that inhalation of formaldehyde at 1 ppm
level resulted in enhanced sensitivity to other allergens in asthmatic patients
[9]. McGwin et al. [63] also confirmed a significant positive association between
formaldehyde exposure and childhood asthma. As such, formaldehyde-induced
asthma may as well be the result of an allergic response. Although some stud-
ies investigated immunoglobulin G (IgG) and/or immunoglobulin E (IgE) an-
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

tibodies to formaldehyde/human serum albumin conjugates, the results were

not consistent [60, 64, 65]. Kim and his team [65] did not find any correlation
between the severity of asthma (and IgE levels) and formaldehyde concentra-
tions in Korean medical students.

4.2. Effect Due to Chronic Exposure

Long-term exposure to elevated levels of formaldehyde, especially in the
occupational setting, has been designated as the cause of irritation and pain
such as upper and lower airway irritation, eye irritation, degenerative dis-
eases, coughing, wheezing, body sores, chest pain, abdominal pain, and loss
of appetite [66–68]. Long-term occupational formaldehyde exposure is also re-
ported to be responsible for such serious and chronic health effects as inflam-
matory and hyperplastic changes of the nasal mucosa, pharyngeal congestion,
chronic pharyngitis, chronic rhinitis, loss of olfactory functioning, lacrima-
tion and cornea disorder, heartburn, tremor, lethargy, etc. [67, 69, 70]. Rager
et al. [71] reported that formaldehyde can alter micro-RNA patterns associ-
ated with regulation of gene expression, potentially leading to the initiation
of a variety of diseases. In a pathologic study conducted by Bono et al. [72],
it was found that exposure to formaldehyde levels above 66 µg m−3 may lead
to oxidative stress as evidenced by the increased levels of malondialdehyde-
deoxyguanosine adduct in leukocytes, a biomarker of oxidative stress and lipid
peroxidation.

4.2.1. Neurotoxicity
Chronic exposure to formaldehyde can be responsible for the symptoms of
neurasthenia which include headaches, dizziness, sleep disorders, and memory
loss. Many reports indicate that chronic exposure to formaldehyde increased
the chances of headache and dizziness by 30%–60% [73–75]. As such, formalde-
hyde appears to have neurotoxic characteristics with systemic toxic effects. It
is thus hypothesized that inhalation of formaldehyde, during the early postna-
tal period, can cause some neurological diseases with aging [76].
It was also recognized that apart from age and gender, environmental
tobacco smoking (ETS) is perhaps the most consistent nongenetic risk factor
 284 K.-H. Kim, S. A. Jahan, and J.-T. Lee

for amyotrophic lateral sclerosis (ALS) [19]; it is a fatal, neurodegenerative

disease caused by the degeneration of motor neurons system that controls
voluntary muscle movement [77]. To examine the association between ETS
and ALS, Wang et al. [78] analyzed data obtained from five different long-term
studies involving a total of more than 1.1 million participants; among those
participants, 832 people were found as ALS patients. In another investigation
conducted by the American Cancer Society’s Cancer Prevention Study II, more
than 1 million individuals were examined over time. Based on this study, it was
concluded that individuals who reported formaldehyde exposure in the work-
place (e.g., beauticians, pharmacists, morticians, chemists, laboratory techni-
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

cians, physicians, veterinarians, dentists, firefighters, photographers, printers,

and nurses) had a 34% higher rate of ALS than the no-exposure group [79].

4.2.2. Cellular Change

Inhalation exposure to formaldehyde causes a number of cellular effects
depending on its concentration and exposure duration. In short-term studies, it
was found that formaldehyde caused cell proliferation in the nasal epithelium
at doses of 2 ppm and above [80, 81]. Cell proliferation is a part of the restora-
tive process to repair cellular damage. In chronic studies, cellular effects, i.e.,
rhinitis (inflammation of the nasal mucosa), epithelial dysplasia (displacement
of one cell type with another one), and squamous metaplasia (replacement of
normal mucosal cells with squamous cells) developed in the nasal cavities of
rats [82] and monkeys [83] after exposures for 12 months and 26 weeks, re-
spectively to 2–3 ppm of formaldehyde. After 24 months of exposure, the inci-
dence of squamous metaplasia in rats increased to nearly 100% [83]. Lacroix
et al. [84] observed abnormal nasal mucosa and nasal secretion on the clinical
assessment of 76 children who had been exposed to urea-formaldehyde foam
insulation. In another human study, Boysen et al. [85] reported that people
who were occupationally exposed to formaldehyde in the range of 0.1–1.1 ppm
showed loss of ciliary activity with the development of squamous metaplasia
from 4 to 9 years. They also found that 25% of the exposed group had swollen
or dry changes of the nasal mucosa. This was characterized histologically as
loss of cilia and goblet cells, squamous metaplasia, and even mild dysplasia.
The mucociliary system represents an important defense mechanism in the
removal of foreign particles and bacteria that enter the upper-respiratory sys-
tem. A reduction in the efficient operation of this defense mechanism, including
formation of squamous metaplasia by exposure to formaldehyde, may increase
the risk of persons exposed to formaldehyde to develop infection and other res-
piratory diseases.

4.2.3. Pulmonary Function Damage

In humans, when exposed repetitively under occupational (or residential)
conditions, formaldehyde has led to symptoms associated with irritation of the
 Human Health Hazards of Formaldehyde 285
upper-respiratory tract and eyes at concentrations between 0.1–3 ppm [86].
Previous studies on repeated human exposure to formaldehyde showed lit-
tle or no convincing evidence of any adverse effects on pulmonary function.
One study of pulmonary function showed small changes (less than 5%–10%)
compared with reference values (exposures in these studies ranged from less
than 1 to about 3.5 ppm) [87]. Kriebel and his team [88] studied 24 physi-
cal therapy students, who were exposed to formaldehyde in breathing zone
at 0.49–0.93 ppm range (during dissection for 3 hr per week over 10 weeks).
The intensity of symptoms from exposure increased in the descending order of
eyes (+43%), nose (+21%), breathing (+20%), throat (+15%), and cough (+5%).
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

Akbar-Khanzadeh and Mlynek [89] also studied 50 nonsmoking first-year med-

ical students exposed to 1.36–2.58 ppm levels of formaldehyde in the breathing
zone. The results showed 82% of the exposed group to suffer from nose irrita-
tion, 76% eye irritation (18% wore goggles), 36% throat irritation, and 14% air-
way irritation. Similarly, factory workers chronically exposed to formaldehyde
at 2.51 ppm levels experienced a decrease in pulmonary ventilation, relative
to a control group [87]. Likewise, with increased exposure over time, ampli-
fied pulmonary damage was seen along with more abnormalities in the small
airways and higher resistance to pulmonary ventilation [67, 70, 86].

4.2.4. Hematotoxicity
Hematotoxicity is defined as toxicity caused by chemical exposure to the
blood and hematopoietic system, often resulting in decreased blood cell counts.
It was demonstrated that long-term exposure of formaldehyde can decrease the
number of white blood cells and possibly lower platelet and hemoglobin counts
[74, 90, 91]. A report by Huang et al. [92] revealed that a previously healthy
woman experienced lower than normal counts of white blood cells, red blood
cells, platelet, and hemoglobin, just after 3 months of moving into a newly
remodeled apartment. The formaldehyde levels in that apartment unit were
about 4 times higher than the national standard set for indoor environment
in China (0.08 ppm). However, such an abnormal pattern was not apparent
for other chemicals (e.g., benzene, toluene, etc.) measured concurrently [93].
In a study targeting occupational exposure (i.e., nurses in hospital), it was
concluded that an inverse correlation between white blood cells and formalde-
hyde concentration is the best indicator of exposure among all the recognized
outcomes [94]. Contrary to this finding, another study reported no signifi-
cant differences in WBC and Hb in potential exposure groups such as wood
workers [73].

4.2.5. Reproductive Toxicity

The potential role of formaldehyde as teratogen and its impacts on hu-
man reproduction are still a matter of scientific controversy. Until recently,
very limited research has been conducted to specifically address such aspects
 286 K.-H. Kim, S. A. Jahan, and J.-T. Lee

of formaldehyde. However, a few studies found menstrual disorder and dys-

menorrhea in women who were occupationally exposed to formaldehyde. Zhou
et al. [95] found that long-term formaldehyde exposure at a dose of 2.46 mg
m−3 should have a harmful effect on the reproductive function of male rats
with a build up of oxidative stress. It is interesting to note that triphlorethol-A
can exert a cytoprotective effect in V79-4 cells against formaldehyde-induced
oxidative stress by inhibiting the mitochondria-mediated caspase-dependent
apoptotic pathway [96].
In a food additive factory, more than 70% of the female employees ex-
posed to formaldehyde through inhalation (0.67–4.5 ppm) reported abnormal
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

menstrual cycles, while only 17% reported such occurrences in the control
group [97]. Likewise, anatomy teachers who were occupationally exposed to
formaldehyde levels around 0.41 to 3.2 ppm also reported painful menstrua-
tion (dysmenorrhea) and increased menstrual flow (with abnormal menstrual
cycles) [75]. In a case-control study, a significant association between spon-
taneous abortion and formalin exposure (odds-ratio 3.5, 95% CI 1.1–11.2,
P = 0.05) was found in Finnish women who worked in pathology or histol-
ogy laboratories for more than 3 days per week [98]. Another study focusing on
female wood workers reported significantly lower fecundability density ratios
(FDR: a ratio of average incidence densities of pregnancies) of 0.64 with 95% CI
(0.43–0.92) in women exposed to high formaldehyde levels, even after adjust-
ments for smoking and alcohol consumption [99]. It is, however, very hard to
find any studies focusing on such effect with respect to the male reproductive
system.

4.2.6. Genotoxicity
It was reported that formaldehyde exposure can induce DNA and chromo-
somal damage in human peripheral blood cells [100–103]. A line of evidence
indicated that formaldehyde itself (not a metabolite) is capable of directly re-
acting with DNA and producing genotoxic effects on portal-of-entry tissues, es-
pecially after exceeding biotransformation capacities [104, 105]. Chinese work-
ers exposed to formaldehyde showed an increase in DNA damage in peripheral
lymphocytes, when measured by single cell gel electrophoresis (Comet assay)
[106, 107]. Several studies have also shown that short-term (8 weeks) exposure
to high levels of formaldehyde (0.41–0.80 ppm) increased micronuclei (MN) fre-
quency in nasal epithelial cells [108, 109], while long-term (1 year) exposure
increased MN frequency in lymphocytes [110, 111].
In a Portuguese case-control study, sister-chromatid exchange and MN
frequencies in peripheral lymphocytes were significantly higher in exposed
subjects (mean formaldehyde level of 0.5 ppm) than the control group [112].
In a recent review study, increased levels of CA were also reported in the
 Human Health Hazards of Formaldehyde 287
peripheral blood lymphocytes of children exposed to formaldehyde in prefab-
ricated schools [113]. Environment Canada/Health Canada [114] and WHO
[115] stated formaldehyde as weakly genotoxic, with effects most likely to be
observed in vivo in cells from tissues or organs after the initial contact.

4.2.7. Carcinogenesis
The possibility of formaldehyde as a carcinogen has been tested through
diverse transmission routes—inhalation, oral administration, topical applica-
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

tion, and subcutaneous injections in rodents. The findings of nasal tumors in

rodents exposed to high levels of airborne formaldehyde led to a concern about
its carcinogenic effects in occupationally exposed workers [116–118]. Based on
comprehensive researches and large-scale human studies conducted interna-
tionally, the International Agency for Research on Cancer (IARC) classified
formaldehyde as a human carcinogen that can cause nasopharyngeal cancer
[104]. According to this classification, formaldehyde is a probable human car-
cinogen under conditions of unusually high or prolonged exposure. The US
National Toxicology Program (NTP) reported formaldehyde as a known human
carcinogen in its 12th Report on Carcinogens [119].
There is sufficient evidence for a linkage between formaldehyde expo-
sure and nasopharyngeal cancer, nasal and paranasal cancer, and leukemias
[120–122]. Schwilk et al. [123] reported the possible link between formalde-
hyde and increased risks of leukemia, of particular myeloid leukemia (relative
risk = 1.53; 95% confidence interval = 1.11 to 2.21; P = 0.005; 14 studies). In-
creased incidences of leukemia have also been reported in several occupational
epidemiologic studies [124–126]. In a case-control study on funeral industry
workers, an association was apparent between increasing formaldehyde expo-
sure and mortality from myeloid leukemia [125]. In another previous study
covering 25,619 industrial workers exposed to formaldehyde occupationally,
it was possible to find an increased risk of death due to leukemia, partic-
ularly myeloid leukemia [127]. In a review based on several meta-analyses,
Zhang et al. [100] concluded a certain linkage between formaldehyde expo-
sure and myeloid leukemia (ML). A cohort study of 11,039 textile workers also
found a certain relationship between the duration of formaldehyde exposure
and leukemia-related deaths [124]. In contrast, another cohort study consist-
ing of 14,014 British industry workers (with an average follow-up period of 11
years) was not able to draw a significant association between the two factors
[128]. Likewise, their possible linkage supported by the National Cancer In-
stitute (NCI) with an aid of both the epidemiologic and the experimental data
was also questioned on the basis of an external comparison of relative risk
trend [129].
 288 K.-H. Kim, S. A. Jahan, and J.-T. Lee

In many occupational cohort studies, there have also been many contra-
dictory findings of formaldehyde effects on cancers of the trachea, bronchus,
lung, buccal cavity, or pharynx [130–132]. Lu et al. [133] found strong evidence
that can support a genotoxic and cytotoxic mode of action for the carcinogene-
sis of inhaled formaldehyde in respiratory nasal epithelium. Meta-analyses for
epidemiological aspects of formaldehyde exposure were not able to reveal any
increased risk of cancer in the oral cavity or lung [134–136]. As formaldehyde
undergoes rapid chemical changes immediately after absorption, some scien-
tists believe that it is unlikely to exert influences on organ sites beyond the
upper respiratory tract.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

5. REFERENCE AND REGULATORY GUIDELINE

OF FORMALDEHYDE EXPOSURE
Occupational and environmental exposure to formaldehyde is a public health
concern that needs to be addressed globally. The advisories, regulations, and
guidelines regarding formaldehyde exposure are summarized in Table 3. The
European Union has adopted a directive that imposes concentration limits
for formaldehyde and paraformaldehyde in cosmetics. These substances are
permitted at a maximal concentration of 0.2% by weight or volume [137]. In
Quebec, Canada, the Regulation Concerning Occupational Health and Safety
established its permissible exposure value in air at 2 ppm as the ceiling (the
value that must never be exceeded during any length of duration whatsoever)
[138]. Guidelines for ambient formaldehyde levels in living spaces have been
set in several countries in the range of 0.05 to 0.4 ppm, with a preference to
0.1 ppm [10].
The US NTP included formaldehyde as an item under consideration for the
12th Report on Carcinogens [139]. In 2006, the IARC reclassified formaldehyde
from Group 2A (probably carcinogenic to humans) to Group 1 (carcinogenic to
humans) [140]. The EPA has classified formaldehyde as a B1 compound, prob-
able human carcinogen, on the basis of limited evidence in humans but with
sufficient evidence in animals [120]. According to the Occupational Safety and
Health Administration, permissible exposure limits for occupational formalde-
hyde exposure are 0.75 ppm at or below an 8-hour time-weighted average and
the short-term exposure limit of 2 ppm [141]. The EPA regulates formalde-
hyde under the Clean Air Act by designating it as a hazardous air pollutant
[142]. The Food and Drug Administration identifies formaldehyde as an in-
direct food additive for use only as a component of adhesives [143]. The food
additive, formaldehyde, if used in accordance with specified conditions, should
be permitted only in the feed and drinking water of animals [143].
 Human Health Hazards of Formaldehyde 289
Table 3: Regulations, Advisories, and Guidelines Applicable to Formaldehyde

Concentration
Country or agency (ppm) Type Reference

Australia 1 TWAa [10]

2 STELb
Belgium 2 Ceilingc [10]
Brazil 1.6 Ceiling [10]
China 0.5 Ceiling [10]
Canada 2 Ceiling [138]
Denmark 0.3 STEL [156]
Finland 0.3 TWA [10]
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

1 Ceiling [10]
France 0.5 TWA [157]
1 STEL
Germany 0.3 TWA [10]
0.6 Ceiling [10]
Hong Kong 0.3 Ceiling [10]
Ireland 2 STEL [10]
Japan 0.5 TWA [10]
Malaysia 0.3 Ceiling [10]
Mexico 2 Ceiling [10]
Netherlands 2 STEL [10]
New Zealand 1 Ceiling [10]
Norway 1 Ceiling [158]
Executive (2002) [133]
Poland 1 Ceiling [10]
South Africa 2 STEL [10]
South Korea 2 STEL [10]
Spain 0.33 STEL [10]
Switzerland 0.6 STEL [10]
United Kingdom 2 STEL [10]
United States [10]
American Conference 0.3 TLVd [160]
of Government
Industrial Hygienists
NIOSH 0.016 TWA [161]
0.1 Ceiling
Occupational Safety 0.75 TWA [141]
and Health
Administration
2 STEL
Environmental 0.7 TLV [162]
Protection Agency

aTWA, time-weighted average; bSTEL, short-term exposure limit; cCeiling, the value that should
never be exceeded during any length of time; and dTLV, threshold limit value.

6. CONCLUSION
As the most commercially important aldehyde, formaldehyde is in great
demand with its global consumption rate growing rapidly with the in-
creased production of wood panels, laminates, pentaerythritol, etc. Exposure to
 290 K.-H. Kim, S. A. Jahan, and J.-T. Lee

formaldehyde can occur via inhalation of its gas (or vapor) form or absorption
of liquid form through the skin. Hence, occupational exposure to formaldehyde
is usually quite high relative to the general public.
Formaldehyde has been widely reported to cause dermal allergic reactions
in occupationally exposed personnel. Although formaldehyde has been classi-
fied as the cause of an irritant-induced asthma, several studies have yet been
unable to find any strong correlation between the severity of asthma (and IgE
levels) and formaldehyde concentrations. Nevertheless, continual exposure to
formaldehyde is suspected to cause various symptoms (i.e., neurasthenia, up-
per and lower airway irritation, inflammatory and hyperplastic changes of
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

the nasal mucosa, coughing, wheezing, expectoration, pharyngeal congestion,

chronic pharyngitis, chronic rhinitis, loss of olfactory functioning, lacrimation,
cornea disorders, hematotoxicity, heartburn, tremors, body sores, chest pain,
lethargy, abdominal pain, and loss of appetite). Although formaldehyde is con-
sidered carcinogenic by some agencies (e.g., IARC, NTP, etc.), epidemiological
studies have not been able to provide sufficient evidence to fully support their
propositions. Several studies concluded that biological evidence is yet inade-
quate to support the relationship between leukemia and formaldehyde expo-
sure. At present, it is likely that low levels (<1 ppm) of formaldehyde can have
only a minimal (or nonexistant) carcinogenic potential on human cancer risk.
As such, further research is necessary to precisely describe its carcinogenicity,
especially with respect to the human body. However, in order to protect the gen-
eral population against acute and chronic sensory irritation due to formalde-
hyde, regulation agencies of different countries should put collaborated efforts
efficiently to establish more reliable guidelines for its control under various
circumstances.

ACKNOWLEDGEMENTS
This study was supported by a National Research Foundation of Korea (NRF)
grant funded by the Ministry of Education, Science and Technology (MEST)
(No. 2009-0093848).

REFERENCES
1. Agency for Toxic Substances and Disease Registry. Toxicological Profile for
Formaldehyde. Agency for Toxic Substances and Disease Registry, US Department of
Health and Human Services; 1999.
2. Bolt HM, Degen GH, Hengstler JG. The carcinogenicity debate on formaldehyde:
How to derive safe exposure limits? Arch Toxicol. 2010; 84(6): 421–422.
3. Bracamonte BG, Ortiz FJ, Diez LI. Occupational allergic contact dermatitis due
to formaldehyde and textile finish resins. Contact Dermatitis. 1995; 33: 139–140.
 Human Health Hazards of Formaldehyde 291
4. California Air Resources Board. Determination of Formaldehyde and Toluene Di-
isocyanate Emissions from Indoor Residential Sources. Research Division, California
Air Resources Board, Sacramento, CA; 1996.
5. Cai Y, Lin S, Jin Y, Chen H, Zheng J, Chen B. Investigation of formaldehyde level
in marketed marine products. Strait J Prevent Med. 2000; 6(5): 32–39.
6. Naya M, Nakanish J. Risk assessment of formaldehyde for the general population
in Japan. Regul Toxicol Pharmacol. 2005; 43(3): 232–248.
7. Dales R, Raizenne M. Residential exposure to volatile organic compounds and
asthma. J Asthma. 2004; 41: 259–270.
8. Arts JHE, Rennen MAJ, de-Heer C. Inhaled formaldehyde: Evaluation of sen-
sory irritation in relation to carcinogenicity. Regul Toxicol Pharm. 2006; 44: 144–
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

160.
9. Casset A, Marchand C, Purohit A, le-Calve S, Uring-Lambert B, Donnay C. In-
haled formaldehyde exposure: Effect on bronchial response to mite allergen in sensi-
tized asthma patients. Allergy. 2006; 61: 1344–1350.
10. American Conference of Government Industrial Hygienists
R Worldwide. Docu-
mentation of the TLVs
R and BEIs
R with Other Worldwide Occupational Exposure
Values—2003. CD-ROM, Cincinnati, OH, American Conference of Government Indus-
trial Hygienists; 2003.
11. Jurvelin JA, Edwards RD, Vartiainen M, Pasanen P, Jantunen MJ. Residential
indoor, outdoor, and workplace concentrations of carbonyl compounds: Relationships
with personal exposure concentrations and correlation with sources. J Air Waste Manag
Assoc. 2003; 53: 560–573.
12. Baumann MGD, Lorenz LF, Batterman SA, Zhang GZ. Aldehyde emissions from
particleboard and medium density fiberboard products. Forest Product J. 2000; 50:
75–82.
13. Atkinson R, Arey J. Gas-phase troposheric chemistry of biogenic volatile organic
compounds: a review. Atmos Environ. 2003; 37: 197–219.
14. Pratt GC, Dymond M, Ellickson K. Validation of a novel air toxic risk model with
air monitoring. J Risk Anal. DOI: 10.1111/j.1539-6924.2011.01640.x
15. Leovic KW, Sheldon LS, Whitaker DA, Hetes RG, Calcagni JA, Baskir JN. Mea-
surement of indoor air emissions from dry-process photocopy machines. J Air Waste
Manag Assoc. 1996; 46: 821–829.
16. Que Z, Furuno T, Katoh S, Nishino Y. The mathematical model for the formalde-
hyde emission from wood-based board in room. Build Environ. 2007; 42(6): 2321–2324.
17. Myers GE. Formaldehyde Release from Wood Products. American Chemical Soci-
ety (ACS) Symposium Series, Washington DC, USA; 1986: 87–106.
18. Agency for Toxic Substances and Disease Registry. Toxicological Profile for
Formaldehyde. Atlanta: Public Health Service, US Department of Health and Human
Services; 2007: 512–521.
19. International Agency for Research on Cancer (IARC). Monographs on the Evalua-
tion of the Carcinogenic Risk of Chemicals to Humans. Wood Dust and Formaldehyde.
Lyon, France: International Association for Research on Cancer; 1995.
20. Agency for Toxic Substance & Disease Registry/Environmental Protection Agency.
Toxicological Profile for Formaldehyde. Dept. of Health and Human Services; July 1999:
468–476.
 292 K.-H. Kim, S. A. Jahan, and J.-T. Lee

21. Turrio-Baldassarri L, Battistelli CL, Conti L, Crebelli R, Berardis BD, Iamiceli

AL, et al. Emission comparison of urban bus engine fueled with diesel oil and “biodiesel”
blend. Sci Total Environ. 2004; 327: 147–162.
22. Baker RR. The generation of formaldehyde in cigarettes—overview and recent
experiments. Food Chem Toxicol. 2006. 44, 1799–1822.
23. Reuss G, Disteldorf W, Gamer AO, Hilt A. Formaldehyde. In: Ullmann’s Ency-
clopedia of Industrial Chemistry, 6th rev. ed., Vol. 15. Weinheim: Wiley-VCH Verlag
GmbH; 2003:1–34.
24. Groah WJ, Bradfield J, Gramp G, Rudzinski R, Heroux G. Comparative response
of reconstituted wood products to European and North American test methods for de-
termining formaldehyde emissions. Environ Sci Technol. 1991; 25: 117–122.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

25. World Health Organization. Formaldehyde (Environmental Health Criteria 89).

Geneva: International Programme on Chemical Safety; 1989.
26. Gerberich HR, Seaman GC. Formaldehyde. In: Kroschwitz JI, Howe-Grant M,
Eds., Kirk–Othmer Encyclopedia of Chemical Technology, 5th ed., Vol. 11. New York:
John Wiley and Sons; 2004: 929–951.
27. Bizzari S. CEH Marketing Research Report: Formaldehyde. 658.5000 A. SRI Inter-
national; 2007: 106.
28. Bizzari S. Formaldehyde. 2010. Available at: http://www.sriconsulting.com/CEH/
Public/Reports/658.5000/.
29. Chemical Information Services. Directory of World Chemical Producers, Dallas,
TX. 2004. Available at: www. chemicalinfo.com.
30. Park B-D, Kang E-C, Park J-Y. Thermal curing behavior of modified urea-
formaldehyde resin adhesives with two formaldehyde scavengers and their influence
on adhesion performance. J App Poly Sci. 2008; 110: 1573–1580.
31. ChemSources. Formaldehyde. Chemical Sources International. 2009. Available at:
http://www.chemsources.com/ (accessed April 30, 2009).
32. ChemSources. Paraformaldehyde. Chemical Sources International. 2009. Avail-
able at: http://www.chemsources.com/ (accessed April 30, 2009).
33. ChemSources. Trioxane. Chemical Sources International. 2009. Available at: http:
//www.chemsources.com/ (accessed April 30, 2009).
34. American Conference of Government Industrial Hygienists. Documentation of the
Threshold Limit Values and Biological Exposure Indices, 7th ed. Cincinnati: Author;
2001: 26.
35. World Health Organization. Formaldehyde. A CICAD (Concise International
Chemical Assessment Document) No. 40. International Programme on Chemical Safety
(IPSC); 2003.
36. Franks SJ. A mathematical model for the absorption and metabolism of formalde-
hyde vapour by humans. Toxicol Appl Pharmacol. 2005; 206: 309–320.
37. Kulle TJ. Acute odor and irritation response in healthy nonsmokers with
formaldehyde exposure. Inhal Toxicol. 1993; 5: 323–332.
38. Paustenbach D, Alarie Y, Kulle T, Schachter N, Smith R, Swenberg J, et al. A rec-
ommended occupational exposure limit for formaldehyde based on irritation. J Toxicol
Environ Heal. 1997; 50: 217–263.
39. Neuss S, Holzmann K, Speit G. Gene expression changes in primary human nasal
epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010; 198(2): 289–295.
 Human Health Hazards of Formaldehyde 293
40. Wolkoff P, Nielsen GD. Non-cancer effects of formaldehyde and relevance for set-
ting an indoor air guideline. Environ Int. 2010; 36(7): 788–799.
41. Speit G, Schutz P, Weber I, Ma-Hock L, Kaufmann W, Gelbke HP, Durrer S.
Analysis of micronuclei, histopathological changes and cell proliferation in nasal ep-
ithelium cells of rats after exposure to formaldehyde by inhalation. Mutat Res. 2011;
721: 127–135.
42. Zhang DZ, Zhang FL, Jin SY, Liu YH. Investigation on the health of workers
occupationally exposed to low level of formaldehyde. Chinese J Ind Hyg Occup Dis.
1999; 17(5): 13–14.
43. Salonen H, Pasanen AL, Lappalainen S, Riuttala H, Tuomi T, Pasanen P. Volatile
organic compounds and formaldehyde as explaining factors for sensory irritation in
office environments. J Occup Environ Hyg. 2009; 6(4): 239–247.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

44. International Programme on Chemical Safety. Formaldehyde. Environmental

Health Criteria 89. Geneva: World Health Organization; 1989.
45. National Poisons Information Service. Formaldehyde. TOXBASE
R ; 2002.
46. Hao G, Liu L, Wu J. Clinical analysis on 17 cases of acute poisoning caused by the
inhalation of formaldehyde. Hebei Med. 1998; 4(6): 58–69.
47. Liu WJ, Song JL. Analysis on a case of formaldehyde poisoning. J Chinese People’s
Pub Secur Uni. 2001; 24: 22–23.
48. Li S, Song Z. An incident of food poisoning in students caused by formaldehyde.
Chinese J Sch Heal. 2006;27: 341–348.
49. Zhang L, Li J, Xu C, Xu J, Liu HF. A research on the formaldehyde residua in
preserved sleeve fish and its influencing factors. Shanghai J Preven Med. 2006; 18(4):
179–183.
50. Cronin E. Formaldehyde is a significant allergen in women with hand eczema.
Contact Dermatitis. 1991; 25(5): 276–282.
51. Meding B, Swanbeck G. Occupational hazard in an industrial city. Contact Der-
matitis. 1990; 22(1): 13–23.
52. Flyvholm MA, Menne T. Allergic contact dermatitis from formaldehyde: A case
study focusing on sources of formaldehyde exposure. Contact Dermatitis. 1992; 27(1):
27–36.
53. Sanchez I, Rodriguez F, Quinones D, Garcia-Abujeta JL, Fernandez L, Martin-
Gil D. Occupational dermatitis due to formaldehyde in newspaper. Contact Dermatitis.
1997; 37(3): 131–132.
54. Scheman AJ, Carroll PA, Brown KH, Osburn AH. Formaldehyde-related textile
allergy: An update. Contact Dermatitis. 1998; 38(6): 332–336.
55. Rudzki E, Rebandel P, Grzywa Z. Patch tests with occupational contactants in
nurses, doctors and dentists. Contact Dermatitis. 1989; 20(4): 247–259.
56. Rastogi SC. A survey of formaldehyde in shampoos and skin creams on the Danish
market. Contact Dermatitis. 1992; 27(4): 235–240.
57. Su H, Zheng R. Four contact dermatitis cases exposed to phenolic aldehyde resin.
J Preven Med. 1995; 1: 1–8.
58. Wu DF, Wu YH. Investigation of dermatitis caused by occupational formaldehyde
exposure. J Labour Med. 2001; 18(4): 226–227.
59. Brooks SM, Hammad Y, Richards I, Giovonco-Barbas J, Jenkins K. The spectrum
of irritant-induced asthma: sudden and not-so sudden onset and the role of allergy.
Chest. 1998; 113: 42–49.
 294 K.-H. Kim, S. A. Jahan, and J.-T. Lee

60. Vandenplas O, Fievez P, Delwiche JP, Boulanger J, Thimpont J. Persistent

asthma following accidental exposure to formaldehyde. Allergy. 2004; 59: 115–116.
61. Yue W, Jin XB, Pan XC, Ding J. Relationship between indoor air formaldehyde
exposure and allergic asthma in adults. Chinese J Pub Heal. 2004; 20(8): 904–906.
62. Rumchev KB, Spickett JT, Bulsara MK, Phillips MR, Stick SM. Domestic exposure
to formaldehyde significantly increases the risk of asthma in young children. Eur Resp
J. 2002; 20(2): 403–408.
63. McGwin G, Lienert J, Kennedy JI. Formaldehyde exposure and asthma in chil-
dren: A systematic review. Environ Health Perspect. 2010; 118(3): 313–317.
64. Krakowiak A, Gorski P, Pazdrak K, Ruta U. Airway response to formaldehyde in-
halation in asthmatic subjects with suspected respiratory formaldehyde sensitization.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

Am J Indus Med. 1998; 33: 274–281.

65. Kim CW, Song JS, Ahn YS, Park SH, Noh JH, Hong CS. Occupational asthma due
to formaldehyde. Yonsei Med J. 2001; 42: 440–445.
66. Dai D, Bao Z. Investigative report on formaldehyde occupational workers. Ind
Heal Occup Dis. 1999; 1: 43–51.
67. Li ZG, Chen BC. Effect of low concentration formaldehyde on the health of work-
ers. Chinese J Ind Med. 2002; 15(5): 302–303.
68. Costa S, Pina C, Coelho P, Costa C, Silva S, Porto B, et al.. Occupational ex-
posure to formaldehyde: Genotoxic risk evaluation by comet assay and micronucleus
test using human peripheral lymphocytes. J Toxicol Environ Health A. 2011; 74: 1040–
1051.
69. Geng Y, Meng X, Li X, Lu G. Occupational damage in densified wood board pro-
ducing field and its effect on workers’ health. Occup Heal. 2004; 20(8): 21–22.
70. Fan W, Zhou Y, Jin F, Du L, Jin X. The health effects of pathologists exposed to
formaldehyde. J Occup Environ Med. 2006; 23(6): 466–468.
71. Rager JE, Smeester L, Jaspers I, Sexton KG, Fry RC. Epigenetic changes induced
by air toxics: Formaldehyde exposure alters miRNA expression profiles in human lung
cells. Environ Health Perspect. 2011; 119(4): 494–500.
72. Bono R, Romanazzi V, Munnia A, Piro S, Allione A, Ricceri F, et al.
Malondialdehyde-deoxyguanosine adduct formation in workers of pathology wards: The
role of air formaldehyde exposure. Chem Res Toxicol. 2010; 23(8): 1342–1348.
73. Feng Y, Wang W, Jiang Z, Hu G, Zhong S, Zhang H. Health status of wood workers
exposed to formaldehyde. Anhui J Preven Med. 1996; 2(2): 99–100.
74. Tang LX, Zhang YS. Health investigation on workers exposed to formaldehyde.
Occup Heal. 2003; 19(7): 34–35.
75. Lu Y, Chen XJ, Yang XY, Xue ZQ. A survey of the effection to teachers’ health
from formaldehyde contact. J Xinjiang Med Uni. 2007; 30(3): 234–237.
76. Songur A, Ozen OA, Sarsilmaz M. The toxic effects of formaldehyde on the nervous
system. Rev Environ Contam Toxicol. 2010; 203: 105–118.
77. Armon C. Smoking may be considered an established risk factor for sporadic ALS.
Neurology. 2009; 73: 1693–1698.
78. Wang H, O’Reilly EJ, Weisskopf MG, Logroscino G, McCullough ML, Thun MJ,
et al. Smoking and risk of amyotrophic lateral sclerosis: A pooled analysis of 5 prospec-
tive cohorts. Arch Neurol. 2011; 68(2): 207–215.
 Human Health Hazards of Formaldehyde 295
79. Weisskopf MG, Morozova N, O’Reilly EJ, McCullough ML, Calle EE, Thun MJ,
Ascherio A. Prospective study of chemical exposures and amyotrophic lateral sclerosis.
J Neurol Neurosurg Psychiatry. 2009; 80: 558–561.
80. Cassee FR, Arts JH, Groten JP, Feron VJ. Sensory irritation to mixtures of
formaldehyde, acrolein, and acetaldehyde in rats. Arch Toxicol. 1996; 70: 329–337.
81. Hester SD, Benavides GB, Yoon L, Morgan KT, Zou F, Barry W, Wolf DC.
Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium. Toxi-
cology 2003; 187(1): 13–24.
82. Appelman LM, Woutersen RA, Zwart A, Falke HE, Feron VJ. One-year inhala-
tion toxicity study of formaldehyde in male rats with a damaged or undamaged nasal
mucosa. J Appl Toxicol. 1988; 8(2): 85–90.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

83. Rusch GM, John J, Clary JJ, Rinehart WE, Bolte HF. A 26-week inhalation toxic-
ity study with formaldehyde in the monkey, rat, and hamster. Toxicol App Pharmacol.
1983; 68(3): 329–343.
84. Lacroix JS, Kurt AM, Pochon N, Bretton C, Lunberg JM, Deshusses J. Neutral
endopeptidase activity and concentration of sensory neuropeptide in the human nasal
mucosa. Eur Arch Otorhinolaryngol. 1995; 252: 465–468.
85. Boysen M, Zadig E, Digernes V, Abeler V, Reith A. Nasal mucosa in workers ex-
posed to formaldehyde: A pilot study. Br J Ind Med. 1990; 47(2): 116–121.
86. Hong Z, Tong Z, Shi J. Effects of formaldehyde on respiratory system and pul-
monary function of workers. Chinese J Pub Heal. 2007; 23(7): 849–850.
87. Wang W, Wang Q, Zhou Y. Effects of low concentration of formaldehyde on res-
piratory system and pulmonary function of workers. Chinese J Ind Med. 2000; 13(2):
115–116.
88. Kriebel D, Sama SR, Cocanour B. Reversible pulmonary responses to formalde-
hyde. A study of clinical anatomy students. Am Rev Respirat Dis. 1993; 148: 1509–1515.
89. Akbar-Khanzadeh F, Mlynek JS. Changes in respiratory function after one and
three hours of exposure to formaldehyde in non-smoking subjects. Occup Environ Med.
1997; 54: 296–300.
90. Tong ZM, Zhu SX, Shi J. Effect of formaldehyde on blood component and blood
biochemistry of exposed workers. Chinese J Ind Med. 2007; 20(6): 409–410.
91. Yang WH. Hemogram of workers exposed to low concentration of formaldehyde.
Prac Preven Med. 2007; 14(3): 792–799.
92. Huang Y, Zou Z, Deng H. An analysis report about peripheral blood anemia in-
duced by excessive formaldehyde in abiding place. Jiangsu Environ Sci Technol. 2007;
20: 16–17.
93. Huang W, Lu Y, Chang X, Bai L, Zhao H, Liu W. Indoor air pollution in newly
redecorated rooms. J Environ Heal. 2007; 24 (2): 101–103.
94. Kuo H, Jian G, Chen C, Liu C, Lai J. White blood cell count as an indicator of
formaldehyde exposure. Bull Environ Cont Toxicol. 1997; 59(2): 261–267.
95. Zhou D, Zhang J, Wang H. Assessment of the potential reproductive toxicity of
long-term exposure of adult male rats to low-dose formaldehyde. Toxicol Ind Health.
2011; 27(7): 591–598.
96. Zhang R, Lee IK, Kang KA, Piao MJ, Kim KC, Kim BJ, et al. Cytoprotective ef-
fects of triphlorethol-A against formaldehyde-induced oxidative damage and apoptosis:
 296 K.-H. Kim, S. A. Jahan, and J.-T. Lee

Role of mitochondria-mediated caspase-dependent pathway. J Toxicol Environ Health

A. 2010; 73(21–22): 1477–1489.
97. Xu SY, Yi GL, Li SH. Hygienic investigation of the effect of formaldehyde on the
workers’ health. Occup Heal. 2007; 23(7): 491–492.
98. Taskinen HK, Kyyronen P, Hemminki K, Hoikkala M, Lajunen K, Lindbohm ML.
Laboratory work and pregnancy outcome. J Occup Med. 1994; 36(3): 311–319.
99. Taskinen HK, Kyyronen P, Sallmen M, Virtanen SV, Liukkonen TA, Huida O.
Reduced fertility among female wood workers exposed to formaldehyde. Am J Ind Med.
1999; 36(1): 206–212.
100. Zhang L, Steinmaus C, Eastmond DA, Xin XK, Smith MT. Formaldehyde expo-
sure and leukemia: A new meta-analysis and potential mechanisms. Muta Res. 2009;
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

681: 150–168.
101. Ladeira C, Viegas S, Carolino E, Prista J, Gomes MC, Brito M. Genotoxicity
biomarkers in occupational exposure to formaldehyde—The case of histopathology lab-
oratories. Mutat Res. 2011; 721: 15–20.
102. Lu K, Moeller B, Doyle-Eisele M, McDonald J, Swenberg JA. Molecular dosime-
try of N2 -hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde. Chem Res
Toxicol. 2011; 24: 159–161.
103. Washam C. Epigenetics of formaldehyde: Altered microRNAs may be key to ad-
verse effects. Environ Health Perspect. 2011; 119: 176–182.
104. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans,
Vol. 88 Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol. 2006. Available
at: http://monographs.iarc.fr/ENG/Monographs/vol88/index.php.
105. Yang Y, Allen BC, Tan YM, Liao KH, Clewell HJ. Bayesian analysis of a rat
formaldehyde DNA-protein cross-link model. J Toxicol Environ Health A. 2010; 73(12):
787–806.
106. Jiang L. Mensuration of indoor formaldehyde pollution of Pingdingshan munici-
pal office building. J Pingdingshan Ins Technol. 2006; 15(3): 38–39.
107. Tong ZM, Shi J, Zhao JS, Yang H, Jiang RM, Kong L. Analysis on genetic toxicity
of formaldehyde on occupational exposure population. Chinese J Pub Heal. 2006; 22(7):
783–784.
108. Cheng Y, Ying C, Yan W, Zhang J, Zhang M. Nasal mucosa epithelial cell and
lymphoblast micronuclei of formaldehyde exposed population. Sanit Antiepid Stat Jing-
sha City. 1995; 14(5): 293–295.
109. Knasmueller S, Holland N, Wultsch G, Jandl B, Burgaz S, Nersesyan A. Use of
nasal cells in micronucleus assays and other genotoxicity studies. Mutagenesis. 2011;
26(1): 231–238.
110. Ye X, Yan W, Xie H, Zhao M, Ying C. Cytogenetic analysis of nasal mucosa cells
and lymphocytes from high-level long-term formaldehyde exposed workers and low-
level short-term exposed waiters. Muta Res. 2005; 588(1): 22–27.
111. Yu LQ, Jiang SF, Leng SG, Zhang CZ, Yan YJ, Niu Y. Early genetic effects on
workers occupationally exposed to formaldehyde. Chinese J Preven Med. 2005; 39(6):
392–395.
112. Costa S, Coelho P, Costa C, Silva S, Mayan O, Santos LS. Genotoxic damage in
pathology anatomy laboratory workers exposed to formaldehyde. Toxicology. 2008; 252:
40–48.
 Human Health Hazards of Formaldehyde 297
113. Neri M, Bonassi S, Knudsen LE, Sram RJ, Holland N, Ugolini D. Children’s ex-
posure to environmental pollutants and biomarkers of genetic damage. II. Overview
and critical issues. Mutat Res. 2006; 612(1): 1–13.
114. Environment Canada/Health Canada. Canadian Environmental Protection Act,
1999. Priority substances list assessment report. Formaldehyde. Government of
Canada, Environment Canada, Health Canada; 2001.
115. World Health Organization. Concise International Chemical Assessment Docu-
ment 40. Formaldehyde. Geneva: Author; 2002.
116. McGregor D, Bolt H, Cogliano V, Richter-Reichhelm HB. Formaldehyde and glu-
taraldehyde and nasal cytotoxicity: case study within the context of the 2006 IPCS
Human Framework for the Analysis of a cancer mode of action for humans. Crit Rev
Toxicol. 2006; 36(10): 821–835.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

117. Jakab MG, Klupp T, Besenyei K, Biro A, Major J, Tompa A. Formaldehyde-

induced chromosomal aberrations and apoptosis in peripheral blood lymphocytes of
personnel working in pathology departments. Mutat Res. 2010; 698(1–2): 11–17.
118. Korobitsyn BA. Multiplicative model for assessment of chemical-induced cancer
risk. Int J Environ Health Res. 2011; 21: 1–21.
119. National Toxicology Program (NTP). Report on Carcinogens, 12th ed. Depart-
ment of Health and Human Services, Public Health Service, National Toxicology Pro-
gram; 2011. Available at: http://ntp.niehs.nih.gov/go/roc12.
120. Integrated Risk Information System. Formaldehyde. Washington, DC: US Envi-
ronmental Protection Agency; 2010. Available at: http://cfpub.epa.gov/ncea/iris drafts/
recordisplay.cfm?deid=223614.
121. Meng F, Bermudez E, McKinzie PB, Andersen ME, Clewell HJ, Parsons BL. Mea-
surement of tumor-associated mutations in the nasal mucosa of rats exposed to varying
doses of formaldehyde. Regul Toxicol Pharmacol. 2010; 57(2–3): 274–283.
122. Thompson CM, Grafstrom RC. Considerations for the implausibility of leukemia
induction by formaldehyde. Toxicol Sci. 2011; 120: 230–232.
123. Schwilk E, Zhang L, Smith MT, Smith AH, Steinmaus C. Formaldehyde and
leukemia: An updated meta-analysis and evaluation of bias. J Occup Environ Med.
2010; 52: 878–886.
124. Pinkerton L, Hein M, Stayner L. Mortality among a cohort of garment workers
exposed to formaldehyde: An update. Occup Environ Med. 2004; 61(3): 193–200.
125. Hauptmann M, Stewart PA, Lubin JH. Morality from lymphohematopoietic ma-
lignancies and brain cancer among embalmers exposed to formaldehyde. J Nat Cancer
Ins. 2009; 101: 1696–1708.
126. Dreyfuss JH. Occupational formaldehyde exposure linked to increased risk of
myeloid leukemia and death. CA Cancer J Clin. 2010; 60(3): 135–136.
127. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. Mortality from lym-
phohematopoietic malignancies among workers in formaldehyde industries. J Nat Can-
cer Ins. 2003; 95(21): 1915–1923.
128. Coggon D, Harris EC, Poole J. Extended follow-up of a cohort of British chemical
workers exposed to formaldehyde. J Nat Cancer Ins. 2003; 95(21): 1608–1615.
129. Marsh GM, Youk AO. Reevaluation of mortality risks from leukemia in the
formaldehyde cohort study of the National Cancer Institute. Regulatory Toxicology and
Pharmacology. 2004; 40(2): 113–124.
 298 K.-H. Kim, S. A. Jahan, and J.-T. Lee

130. Gardner MJ, Pannett B, Winter PD, Cruddas AM. A cohort study of workers
exposed to formaldehyde in the British chemical industry: An update. Br J Indus Med.
1993; 50: 827–834.
131. Andjelkovich DA, Shy CM, Brown MH, Jansen DB, Richardson RB. Mortality
of iron foundry workers. III. Lung cancer case-control study. J Occup Med. 1994; 36:
1301–1309.
132. Hansen J, Olsen JH. Formaldehyde and cancer morbidity among male employees
in Denmark. Cancer Causes Control. 1995; 6: 354–360.
133. Lu K, Collins LB, Ru H, Bermudez E, Swenberg JA. Distribution of DNA adducts
caused by inhaled formaldehyde is consistent with induction of nasal carcinoma but not
leukemia. Toxicol Sci. 2010; 116(2): 441–451.
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

134. Blair A, Saracci R, Stewart PA. Epidemiologic evidence on the relationship

between formaldehyde exposure and cancer. Scand J Work Environ Hea. 1990; 16:
381–393.
135. Partanen T. Formaldehyde exposure and respiratory cancer- a meta-analysis of
the epidemiologic evidence. Scand J Work Environ Heal. 1993; 19: 8–15.
136. Andersen ME, Clewell HJ, Bermudez E, Dodd DE, Willson GA, Campbell JL,
Thomas RS. Formaldehyde: Integrating dosimetry, cytotoxicity, and genomics to un-
derstand dose-dependent transitions for an endogenous compound. Toxicol Sci. 2010;
118(2): 716–731.
137. European Union. Commission of the European Communities No
2008/0025. Regulation of the European Parliament and of the Council: On cos-
metic products. 2008. Available at: http://ec.europa.eu/enterprise/cosmetics/doc/
com 2008 49/com 2008 49 en.pdf.
138. Regulation Concerning Occupational Health and Safety. Government of Quebec.
Regulations on health and safety. Gazette officielle du Québec, Part 2, Laws and Regu-
lations 133: 5020–33. Quebec; 2001.
139. NTP. Final report on carcinogens background document for formaldehyde. Re-
search Triangle Park, NC: US Department of Health and Human Services, Public
Health Service, National Toxicology Program; 2010. Available at: http://ntp.niehs.nih.
gov/ntp/roc/twelfth/2009/November/Formaldehyde BD Final.pdf.
140. IARC. A review of human carcinogens—Part F: Chemical agents and related
occupations. International Agency for Research on Cancer; 2009. Available at: http:
//monographs.iarc.fr/pdfnews/WG-100F.pdf.
141. Occupational Safety and Health Administration. Toxic and hazardous sub-
stances. Formaldehyde. Occupational Safety and Health Administration. Code of Fed-
eral Regulations. 29 CFR 1910.1048. 2007.
142. Environmental Protection Agency. Designation of hazardous substances. US En-
vironmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 2008. Avail-
able at: http://www.epa.gov/lawsregs/search/40cfr.html.
143. Food and Drug Administration. EAFUS: A food additive database. US Food and
Drug Administration. 2008. Available at: http://vm.cfsan.fda.gov/∼dms/eafus.html.
144. Carraro E, Gasparini S, Gilli G. Identification of a chemical marker of environ-
mental exposure to formaldehyde. Environ Res. 1999; 80: 132–137.
145. Vinzents P, Laursen B. A national cross-sectional study of the working environ-
ment in the Danish wood and furniture industry—Air pollution and noise. Ann Occup
Hyg. 1993; 37: 25–34.
 Human Health Hazards of Formaldehyde 299
146. Malaka T, Kodama AM. Respiratory health of plywood workers occupationally
exposed to formaldehyde. Arch Environ Heal. 1990; 45(5): 288–294.
147. Wu P-C, Li Y-Y, Lee C-C, Chiang C-M, Su H-JJ. Risk assessment of formaldehyde
in typical office buildings in Taiwan. Indoor Air. 2003; 13: 359–363.
148. Burgaz, S, Cakmak G, Erdem O, Yilmaz M, Karakaya AE. Micronuclei frequen-
cies in exfoliated nasal mucosa cells from pathology and anatomy laboratory workers
exposed to formaldehyde. Neoplasma. 2001; 48: 144–147.
149. Milton DK, Walters MD, Hammond K, Evans JS. Worker exposure to endotoxin,
phenolic compounds, and formaldehyde in a fiberglass insulation manufacturing plant.
Am Ind Hygiene Assoc J. 1996; 57: 889–896.
150. Anderson LG, Lanning JA, Barrell R, Miyagishima J, Jones RH, Wolfe P. Sources
Downloaded by [Ki-Hyun Kim] at 12:57 22 November 2011

and sinks of formaldehyde and acetaldehyde: An analysis of Denver’s ambient concen-

tration data. Atmos Environ. 1996; 30: 2113–2123.
151. Bolstad-Johnson DM, Burgess JL, Crutchfield CD, Storment S, Gerkin R, Wilson
JR. Characterization of firefighter exposures during fire overhaul. Am Ind Hyg Assoc J.
2000; 61: 636–641.
152. Suruda A, Schulte P, Boeniger M, Hayes RB, Livingston GK, Steenland K, et al.
Cytogenetic effects of formaldehyde exposure in students of mortuary science. Cancer
Epidemiol Biomark Preven. 1993; 2: 453–460.
153. Wiglusz R, Nikel G, Igielska B, Sitko E. Volatile organic compound emis-
sions from particleboard veneered with decorative paper foil. Holzforschung. 2002; 56:
108–110.
154. Kim S, Kim H-J. Comparison of formaldehyde emission from building finish-
ing materials at various temperatures in under heating system. Indoor Air. 2005; 15:
317–325.
155. Kelly TJ, Smith DL, Satola J. Emission rates of formaldehyde from materials and
consumer products found in California homes. Environ Sci Technol. 1999; 33: 81–88.
156. Arbejdstilsynet [Danish Working Environment Authority]. Limit Values for Sub-
stances and Material, Copenhagen, WEA-Guide; 2002.
157. Institut national de Recherche et de Securite. Threshold Limit Values for Occu-
pational Exposure to Chemicals in France; 2005.
158. Health & Safety Executive. Occupational Exposure Limits 2002 (EH40/2002).
Norwich: Her Majesty’ Stationery Office; 2002.
159. Suva G, Luzern A. Swiss Accident Insurance (Swiss OELs); 2003.
160. American Conference of Government Industrial Hygienists. Formaldehyde.
Threshold limit values for chemical substances and physical agents and biological ex-
posure indices. Cincinnati: Author; 2007: 31.
161. NIOSH. Formaldehyde. NIOSH Pocket Guide to Chemical Hazards. Atlanta, GA:
National Institute for Occupational Safety and Health, Centers for Disease Control and
Prevention; 2005. Available at: http://www.cdc.gov/niosh/npg/.
162. Environmental Protection Agency. Acute exposure guideline levels (AEGLs).
Washington, DC: Office of Pollution Prevention and Toxics, US Environmental Protec-
tion Agency; 2007. Available at: http://www.epa.gov/oppt/aegl/pubs/compiled.pdf.

View publication stats