Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

Formaldehyde

CAS No. 50-00-0

Known to be a human carcinogen

First listed in the Second Annual Report on Carcinogens (1981)

H2C=O

Carcinogenicity 

Formaldehyde is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans and supporting data on mechanisms of carcinogenesis. Formaldehyde was 

first listed in the Second Annual Report on Carcinogens in 1981 as 

reasonably anticipated to be a human carcinogen based on sufficient 

evidence from studies in experimental animals. Since that time, additional cancer studies in humans have been published, and the listing status was changed to known to be a human carcinogen in the 

Twelfth Report on Carcinogens (2011).

Cancer Studies in Humans

Epidemiological studies have demonstrated a causal relationship between exposure to formaldehyde and cancer in humans. Causality is 

indicated by consistent findings of increased risks of nasopharyngeal 

cancer, sinonasal cancer, and lymphohematopoietic cancer, specifically myeloid leukemia among individuals with higher measures of exposure to formaldehyde (exposure level or duration), which cannot be 

explained by chance, bias, or confounding. The evidence for nasopharyngeal cancer is somewhat stronger than that for myeloid leukemia.

Numerous epidemiological studies have evaluated the relationship 

between exposure to formaldehyde and cancer risk, including (1) cohort and nested case-control studies of industrial workers, (2) cohort 

and nested case-control studies of professional groups such as pathologists, funeral directors, or embalmers, and (3) population-based 

cohort and case-control studies. The most informative occupationbased studies are the National Cancer Institute (NCI) cohort of over 

25,000 men and women who worked at companies that used or produced formaldehyde (Hauptmann et al. 2003, 2004, Beane Freeman 

et al. 2009) and the NCI nested case-control study of lymphohematopoietic cancer in embalmers (Hauptmann et al. 2009), because these 

are the only studies that evaluated quantitative exposure-response 

relationships. Occupational exposure to formaldehyde has also been 

evaluated in two other large cohort studies: (1) a National Institute 

for Occupational Safety and Health (NIOSH) cohort study of over 

11,000 male and female garment workers, which evaluated risks of 

cancer at a few selected tissue sites by time since first exposure (latency), exposure duration, and year of first exposure (Pinkerton et 

al. 2004), and (2) a British cohort study of over 14,000 male chemical workers, which evaluated cancer risks by classification of workers 

as “ever exposed” or “highly exposed” (Coggon et al. 2003). In addition, occupational exposure has been evaluated in numerous smaller 

cohort studies. Most of the studies, including all of the large cohort 

studies and the studies of professional groups, reported cancer mortality. For types of cancer with higher survival rates, such as lymphohematopoietic cancer, studies reporting mortality are less informative 

than studies reporting incidence, because mortality studies will miss 

cases of cancer that do not result in death.

For evaluating rare types of cancer, such as nasopharyngeal and 

sinonasal cancer, the collective body of population- and occupationbased case-control studies is more informative than the cohort studies. Particularly useful are the pooled analyses of 12 case-control 

studies of sinonasal cancer by Luce et al. (2002) and the populationbased case-control study by Vaughan et al. (2000) evaluating different 

histological subtypes of nasopharyngeal cancer. In general, metaanalyses and smaller occupational cohort studies have limited utility 

for cancer assessment, because they only reported risks for workers 

“ever exposed” and could not evaluate exposure-response relationships. However, the meta-analysis for lymphohematopoietic cancers 

by Zhang et al. (2009) is more informative because it used data for 

individuals with the highest exposure to formaldehyde to calculate 

the summary relative risks. 

Nasopharyngeal Cancer

Nasopharyngeal cancer is a rare cancer, with an annual incidence of 

less than 1 per 100,000 in most parts of the world. Therefore, casecontrol studies are most useful for evaluation of nasopharyngeal 

cancer risk. Histological subtypes of nasopharyngeal cancer include 

differentiated keratinizing squamous-cell carcinoma, differentiated 

non-keratinizing carcinoma, and undifferentiated non-keratinizing 

carcinoma. In southern China and some parts of Southeast Asia and 

Northern Africa, nasopharyngeal cancer is endemic, with a higher 

proportion of non-keratinizing and undifferentiated subtypes than 

in low-risk areas (Vaughan et al. 1996, Bray et al. 2008). Differentiated keratinizing squamous-cell carcinoma has been associated with 

chemical exposures, such as alcohol consumption and tobacco smoking, whereas non-keratinizing subtypes are more strongly associated 

with Epstein-Barr virus and familial history (which can be related to 

genetic susceptibility and/or common environmental factors). Studies on nasopharyngeal cancer and formaldehyde exposure have been 

conducted in the United States, Europe, and Asia.

Evidence that formaldehyde causes nasopharyngeal cancer 

comes from (1)  consistent findings of increased risk among individuals with the highest formaldehyde exposure in numerous casecontrol studies (Vaughan et al. 1986, 2000, Roush et al. 1987, West 

et al. 1993, Hildesheim et al. 2001), (2) excess cancer mortality associated with formaldehyde exposure in the NCI cohort of industrial 

workers (Hauptmann et al. 2004), and (3) findings of positive exposure-response relationships in a large multi-center case-control study 

(Vaughan et al. 2000) and in the NCI cohort (Hauptmann et al. 2004).

The multi-center case-control study by Vaughan et al. (2000) is 

especially informative, because it had the largest number of cancer 

cases in formaldehyde-exposed individuals, and the analysis was stratified by histological subtype and used several different measures of 

exposure to evaluate risk. In this study, formaldehyde exposure was 

associated with differentiated squamous-cell carcinoma and unspecified subtypes of nasopharyngeal cancer, but not with non-keratinizing and undifferentiated subtypes. The risk of nasopharyngeal cancer 

(differentiated squamous-cell carcinoma and unspecified subtypes) 

increased significantly with increasing cumulative exposure (Ptrend = 

0.033), duration of exposure (Ptrend = 0.014), and probability of exposure (possible, probable, or definite). The odds ratio (OR) was 1.6 

(95% confidence interval [CI] = 1.0 to 2.8, 61 exposed cases) for possible, probable, or definite exposure, increasing to 2.1 (95% CI = 1.1 

to 4.2, 27 exposed cases) for probable or definite exposure, and 13.3 

(95% CI = 2.5 to 70, 10 exposed cases) for definite exposure. 

Other studies also found the highest risks of nasopharyngeal cancer for individuals with the highest formaldehyde exposure levels (assessed as cumulative exposure, exposure level, or exposure score) 

(Vaughan et al. 1986, Roush et al. 1987) and/or longest exposure 

durations (Vaughan et al. 1986, West et al. 1993 [after lagging exposures for 10 years]). Risks were also significantly elevated for individuals with longer time since first exposure (West et al. 1993) or 

who died at an older age (Roush et al. 1987); risk was increased fourfold for individuals who died after the age of 68 and were probably 

Table of Contents: http://ntp.niehs.nih.gov/go/roc12

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Report on Carcinogens, Twelfth Edition (2011)

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exposed to high levels of formaldehyde for at least 20 years before 

death. The associations between formaldehyde exposure and nasopharyngeal cancer remained after adjustment for or consideration 

of potential confounding by tobacco smoking (Vaughan et al. 1986, 

2000, West et al. 1993, Hildesheim et al. 2001) or by exposure to wood 

dust (West et al. 1993, Vaughan et al. 2000, Hildesheim et al. 2001). 

Not all of the estimates of increased risk were statistically significant, and some studies (Armstrong et al. 2000, Li et al. 2006, Hauptmann et al. 2009) did not find an association between formaldehyde 

exposure and nasopharyngeal cancer. However, most of these studies were limited by small numbers of individuals exposed to formaldehyde. The overall consistency of the findings argues against their 

being attributable to chance.

Excess mortality from nasopharyngeal cancer was found in the 

NCI cohort of industrial workers exposed to formaldehyde (standardized mortality ratio [SMR] = 2.10, 95% CI = 1.05 to 4.21). Relative risk increased with increasing cumulative exposure (Ptrend = 0.025 

across exposed subjects), peak exposure (Ptrend < 0.001), and average 

exposure (Ptrend = 0.066) (Hauptmann et al. 2004). Of the 7 exposed 

workers who died of nasopharyngeal cancer, all were in the highest 

peak-exposure category, and 6 were in the highest average-exposure 

category. Controlling for co-exposure to 11 potential occupational 

carcinogens and for plant did not alter the exposure-response relationships for nasopharyngeal cancer. Although the cohort included 

workers in 10 plants, most of the cases of nasopharyngeal cancer occurred in workers in the plant with the largest numbers of workers 

in the highest formaldehyde exposure category; 46% of workers at 

Plant 1 were in the highest peak-exposure category, compared with 

20.1% of workers in all other plants (Stewart et al. 1990, Marsh and 

Youk 2005). A nested case-control study of nasopharyngeal cancer 

among workers in Plant 1 found a significantly elevated risk for ever 

having worked in silversmithing jobs before or after employment at 

Plant 1; however, silversmithing was not correlated with formaldehyde exposure levels at this plant and therefore was not a confounding factor for formaldehyde exposure (Marsh et al. 2007).

No excesses of nasopharyngeal cancer mortality were found in 

the other large cohort studies (Coggon et al. 2003, Pinkerton et al.

2004); however, the statistical power of these studies was inadequate 

to evaluate the risks of rare types of cancer. 

Sinonasal Cancer 

Sinonasal cancer is a rare cancer, with an annual incidence of about 

1 per 100,000, and case-control studies therefore are most useful for 

evaluation of risk. Sinonasal cancer includes cancers of the paranasal sinus and the nasal cavity; the two major histological types are 

adenocarcinoma and squamous-cell carcinoma. 

The evidence that formaldehyde exposure causes sinonasal cancer 

comes from consistent findings of increased risk in population-based 

case-control studies (Olsen et al. 1984, Olsen and Asnaes 1986, Hayes 

et al. 1986, Roush et al. 1987, Luce et al. 1993) and a pooled analysis 

of 12 case-control studies (Luce et al. 2002) that found an excess of 

sinonasal cancer. In most studies, estimates of increased risk were 

statistically significant for individuals ever exposed to formaldehyde, 

or with higher probabilities or levels of exposure (Olsen et al. 1984, 

Olsen and Asnaes 1986, Hayes et al. 1986, Luce et al. 1993, 2002).

Elevated risks were observed for both adenocarcinoma and 

squamous-cell carcinoma; however, some studies suggested that adenocarcinoma was more strongly associated with formaldehyde exposure than was squamous-cell carcinoma (Luce et al. 1993, 2002). The 

pooled analysis (which included studies by Hayes et al. 1986, Vaughan 

et al. 1986, and Luce et al. 1993) was especially informative for evaluating sinonasal cancer, because it had greater statistical power for 

evaluating risks of rare cancers than did the individual studies, and 

it used an independent exposure analysis to assess cumulative exposure, rather than relying on the exposure estimates from the original 

studies. In the pooled analysis, the relative risk of adenocarcinoma 

increased with increasing cumulative exposure; the odds ratios for 

individuals with high cumulative exposure were 3.0 (95% CI = 1.5 to 

5.7, 91 exposed cases) for men and 6.2 (95% CI = 2.0 to 19.7, 5 exposed cases) for women. Support for a positive exposure-response relationship also comes from a case-control study in France that found 

higher risks of sinonasal cancer (adenocarcinoma) among individuals 

with higher average exposure levels and earlier dates of first exposure 

(Luce et al. 1993) and from a case-control study in the Netherlands 

that found a significantly (P < 0.05) higher relative risk of all sinonasal cancer or squamous-cell carcinoma among individuals with 

“high” exposure than those with “low” exposure (Hayes et al. 1986).

Although co-exposure to wood dust is a potential confounding 

factor for sinonasal cancer, and specifically for adenocarcinoma, increased risk of sinonasal cancer associated with formaldehyde exposure has been found among individuals with little or no exposure 

to wood dust or after adjustment for wood-dust exposure (Olsen et 

al. 1984, Hayes et al. 1986, Olsen and Asnaes 1986). Some studies 

suggested that co-exposure to formaldehyde and wood dust had an 

interactive (synergistic) carcinogenic effect (Luce et al. 1993, 2002). 

Two case-control studies did not find an association between formaldehyde exposure and sinonasal cancer; however, one study included 

only 12 cases of sinonasal cancer in exposed individuals (Vaughan 

et al. 1986), and the other had methodological limitations (Pesch et 

al. 2008). In the cohort studies of industrial workers (including studies of the large NCI, NIOSH, and British cohorts) and professional 

groups, the statistical power to detect an association between formaldehyde exposure and sinonasal cancer was limited. Nonetheless, 

a statistically significant excess of sinonasal cancer incidence was 

found among Danish male workers exposed to formaldehyde and 

who were unlikely to have been exposed to wood dust (Hansen and 

Olsen 1995, 1996), and a nonsignificant excess of mortality from sinonasal cancer was found in the NCI cohort. No excess mortality 

from sinonasal cancer was found in the other cohort studies; however, the statistical power of these studies was inadequate to evaluate the risks of types of cancer.

Lymphohematopoietic Cancer

Evidence that demonstrates an association between formaldehyde exposure and combined lymphohematopoietic cancer is as follows: (1) 

in the NCI cohort of industrial workers, risk was significantly higher 

for the highest peak-exposure group than the lowest peak-exposure 

group, and a positive exposure-response relationship based on peak 

exposure was found (Beane Freeman et al. 2009), (2) increased risks 

were found in all of the cohort studies of professional groups (NTP 

2010), and (3) a significant risk was reported (relative risk [RR] = 1.25, 

95% CI = 1.12 to 1.39) in the meta-analysis by Zhang et al. (2009). 

In the NCI cohort study of industrial workers, the risks of Hodgkin’s lymphoma and multiple myeloma also were significantly higher 

among individuals with the highest peak exposure than those with 

the lowest peak exposure, and a positive exposure-response relationship was found for Hodgkin’s lymphoma (Beane Freeman et al. 2009). 

The other studies gave conflicting results for these two types of cancer. 

In the meta-analyses by Zhang et al. (2009), a significant association 

was found for multiple myeloma, but not for Hodgkin’s lymphoma. 

Because the evidence for these two types of cancer is mainly limited to the NCI cohort study, a causal association is not established.

Increased risks for leukemia (all types combined) were found in all 

of the professional studies and some of the industrial cohort studies 
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National Toxicology Program, Department of Health and Human Services

(NTP 2010). Among studies that evaluated subtypes of lymphohematopoietic cancer or leukemia, the strongest associations were observed for myeloid leukemia. For example, in the nested case-control 

study of embalmers (Hauptman et al. 2009), the excess risk of nonlymphoid lymphohematopoietic cancer was explained by a strong association with myeloid cancer, and in other studies, the magnitudes 

of the effect estimates were higher for myeloid leukemia than for all 

leukemia or other subtypes of leukemia (Pinkerton et al. 2004, Beane 

Freeman et al. 2009, NTP 2010). 

The most informative studies for evaluation of the risk of myeloid 

leukemia are the large cohort studies of industrial workers (the NCI, 

NIOSH, and British cohorts) and the NCI nested case-control study 

of lymphohematopoietic cancer in embalmers. Three of these four 

studies found elevated risks of myeloid leukemia among individuals 

with high exposure to formaldehyde, as well as positive exposureresponse relationships. Confounding is unlikely to explain these increased risks, because there was no evidence of potential confounding 

in the individual studies, and the increased risks were observed for 

workers in different industries and occupations (workers at formaldehyde-producing companies, garment workers, and embalmers). 

Both the NCI cohort study of industrial workers and the nested 

case-control study of myeloid leukemia in embalmers found positive 

exposure-response relationships between myeloid leukemia and peak 

formaldehyde exposure level. In the study of embalmers, relative risk 

also increased with increasing duration of employment in embalming (Ptrend = 0.020) and with increasing average exposure level (Ptrend = 

0.058), in addition to increasing peak exposure level (Ptrend = 0.036). 

In analyses using a comparison group of funeral directors with fewer 

than 500 lifetime embalmings, significantly elevated risks of myeloid 

leukemia (adjusted for smoking) were found among workers with longest duration of employment in embalming (OR = 3.9, 95% CI = 1.2 to 

12.5, P = 0.024) and the highest cumulative exposure to formaldehyde 

(OR = 3.1, 95% CI = 1.0 to 9.6, P = 0.047). In addition, elevated risk 

estimates of borderline statistical significance were found for those 

who had performed the largest numbers of embalmings (OR = 3.0, 

95% CI = 1.0 to 9.2, P = 0.057). In a 1994 update of the NCI cohort 

study (based on reanalyses that included additional deaths and recoding of deaths), risk was significantly higher for the highest category 

of peak exposure (RR = 2.79, 95% CI = 1.08 to 7.21) than for the lowest exposure category, and risk increased with increasing peak exposure (Ptrend = 0.02) (Beane Freeman et al. 2009). In a 2004 follow-up 

study, elevated risk estimates were still observed, but the magnitude 

of the association between formaldehyde exposure and myeloid leukemia decreased as time since the last known exposure increased to 

at least 24 years. This pattern is consistent with a follow-up period 

longer than the optimal latency period for cancer, as has been seen 

with other leukemia-inducing agents (Silver et al. 2002). Controlling 

for co-exposure to 11 potential occupational carcinogens did not alter the findings for myeloid leukemia. 

In the NIOSH cohort study of garment workers, elevated risks 

of death from myeloid leukemia were found for all workers and for 

subgroups of workers with the highest exposure or longest latency. 

SMRs were highest among workers with longer exposure duration 

(≥ 10 years), longer time since first exposure (≥ 20 years), or earlier 

year of first exposure (before 1963, when exposure levels were higher). 

In an analysis that included all causes of death listed on the death 

certificate (rather than just the underlying cause), the risk of death 

from myeloid leukemia was significantly increased for workers who 

had been exposed for at least 10 years (SMR = 2.24, 95% CI = 1.02 to 

4.25, 9 deaths) and was concentrated among workers with time since 

first exposure of at least 20 years who had been exposed for at least 10 

years (SMR = 2.55, 95% CI = 1.10 to 5.03, 8 deaths) (Pinkerton et al. 

2004). In the large cohort of British chemical workers, no increased 

risk of leukemia was found for formaldehyde exposure. However, this 

study did not evaluate myeloid leukemia specifically, and exposureresponse analyses were limited; exposure was assessed as “high” or 

“ever,” and the assessment was not calendar-year-specific (Coggon 

et al. 2003). Only one case-control study reported specific findings 

for myeloid leukemia; an excess risk was found for chronic (but not 

acute) myeloid leukemia, based on small numbers of formaldehydeexposed individuals with leukemia (Blair et al. 2001). 

Although several meta-analyses have been published, none has 

included the nested case-control study of myeloid leukemia among 

embalmers by Hauptmann et al. (2009). The most informative metaanalysis (Zhang et al. 2009) found a significantly elevated risk of myeloid leukemia (summary RR = 1.90, 95% CI = 1.31 to 2.76, P = 0.001) 

across studies using risk estimates, when available, for workers with 

the highest formaldehyde exposure. A meta-analysis by Bachand et al. 

(2010) did not find a significantly elevated risk of myeloid leukemia 

(summary RR = 1.09, 95% CI = 0.84 to 1.40); however, this analysis 

did not include the proportionate-mortality cohort studies (studies 

that compared the proportions of deaths between the study population and a reference population), which reported increased risks of 

myeloid leukemia. Bosetti et al. (2008) found an elevated risk of leukemia across studies of professional groups but not across studies of 

industrial workers. This finding is consistent with observations that 

embalmers have longer duration of exposure and higher cumulative 

exposure and are more likely to be exposed to peak exposure levels 

greater than 4 ppm than are industrial workers, and that cancer risk 

is associated with peak levels of exposure to formaldehyde (Hauptmann et al. 2009).

Cancer at Other Tissue Sites

The association between formaldehyde exposure and cancer at other 

tissue sites is weaker than for nasal or lymphohematopoietic cancer 

(see NTP 2010 for a review of the studies). Increased risks of head 

and neck cancers (of the buccal cavity, pharynx, larynx, or combinations of these sites) were observed in many of the cohort and casecontrol studies, but most were not statistically significant, and there 

were no consistent findings of higher risk among the individuals with 

the highest exposure levels. An excess of brain cancer mortality was 

found in all studies of professional groups, but not in the cohort studies of industrial workers, and no positive exposure-response relationship was found in the NCI nested case-control study of brain cancer 

among embalmers. Findings for lung cancer were inconsistent, and 

the data were inadequate to evaluate the association between formaldehyde exposure and cancer at other tissue sites.

Cancer Studies in Experimental Animals

There is sufficient evidence for the carcinogenicity of formaldehyde 

from studies in experimental animals. Formaldehyde caused tumors 

in two rodent species, at several different tissue sites, and by two different routes of exposure. Long-term inhalation exposure to formaldehyde caused nasal tumors, both benign (polypoid adenoma) and 

malignant (predominantly squamous-cell carcinoma but also adenocarcinoma and carcinoma) in male and female F344 rats (Kerns et 

al. 1983, Monticello et al. 1996, Kamata et al. 1997), male SpragueDawley rats (Sellakumar et al. 1985), and male B6C3F1

 mice (Kerns et 

al. 1983). Nasal tumors were also observed after short-term exposure 

(13 weeks) in male Wistar rats (Feron et al. 1988). Although the increased incidences of nasal tumors in mice and in the short-exposure 

study in rats were not statistically significant, they were considered to 

be biologically significant because of the rarity of this type of tumor. 
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National Toxicology Program, Department of Health and Human Services

Long-term exposure of adult rats to formaldehyde in drinking 

water caused benign tumors of the forestomach (squamous-cell 

papilloma) in male Wistar rats (Takahashi et al. 1986) and testes 

(interstitial-cell adenoma) (Soffritti et al. 2002, statistics reported in 

IARC 2006) in male Sprague-Dawley rats. Increased incidences of 

intestinal tumors (primarily leiomyosarcoma, which are rare malignant tumors of the muscle of the intestine) were observed in female 

Sprague-Dawley rats exposed to formaldehyde in utero starting on 

gestational day 13 and throughout life via the drinking water (Soffritti et al. 1989, statistics reported in IARC 2006). Leiomyosarcoma 

of the stomach and intestines was also observed in the formaldehydeexposed groups, but not the concurrent control groups (untreated 

animals and control animals given methanol), in Sprague-Dawley 

rats exposed as adults. Although the findings were not statistically 

significant, they are of concern because of the rarity of these tumors. 

Hemolymphoreticular tumors (combined types) in rats of both sexes 

also were significantly increased after long-term exposure of adults; 

however, it is unclear whether these tumors were exposure-related, 

because of limitations in the reporting of these tumors (Soffritti et 

al. 2002, IARC 2006). In tumor promotion and co-carcinogenicity 

studies, formaldehyde was shown to promote tumors of the stomach and lung in rats (NTP 2010). 

Other Relevant Data

Formaldehyde exposure occurs from both endogenous and exogenous sources. It is rapidly absorbed after inhalation and oral exposure; 

however, it is poorly absorbed via the skin (NTP 2010). The half-life 

of formaldehyde in the plasma of rats and monkeys is about 1 to 1.5 

minutes (McMartin et al. 1979, IARC 2006). Differences in breathing patterns across species may affect differences in absorption and 

distribution. In rats, almost all inhaled formaldehyde is absorbed in 

the nasal passage, whereas in primates, some absorption occurs in 

the trachea and proximal regions of the major bronchi (Chang et al.

1983, Heck et al. 1983, Monticello et al. 1989, Casanova et al. 1991). 

The metabolism of formaldehyde is similar in all mammalian species 

studied (IARC 2006). Although pure formaldehyde is a gas at room 

temperature, it hydrates rapidly and is in equilibrium with its hydrated form, methanediol (Fox 1985); at room and body temperatures, 

the dominant form is methanediol. Formaldehyde is rapidly metabolized by glutathione-dependent formaldehyde dehydrogenase (also 

known as alcohol dehydrogenase 5, ADH5) and S-formyl-glutathione 

hydrolase to formic acid, which enters the one-carbon pool and can 

be either excreted in the urine or oxidized to carbon dioxide and exhaled. ADH5 has been detected in all human tissues at all stages of 

development, from embryo through adult (Thompson et al. 2009). 

Although formaldehyde is rapidly metabolized, it is an electrophile 

that reacts with a variety of endogenous molecules, including glutathione, proteins, nucleic acids, and folic acid (NTP 2010).

Studies on Mechanisms of Carcinogenesis

The mechanisms by which formaldehyde causes cancer are not completely understood and most likely involve several modes of action. 

Formaldehyde exposure is associated with key events related to carcinogenicity, such as DNA reactivity, gene mutation, chromosomal 

breakage, aneuploidy, epigenetic effects (binding to lysine residues 

of histones), glutathione depletion, oxidative stress, and cytotoxicityinduced cellular proliferation (Lu et al. 2008, Guyton et al. 2009, NTP 

2010). Understanding of the mechanisms is more advanced for nasal 

tumors than for lymphohematopoietic cancer. There is evidence for 

a genotoxic mode of action for both types of cancer. Formaldehyde 

is a direct-acting genotoxic compound and has given positive results 

for almost all genetic end points evaluated in bacteria, yeast, fungi, 

plants, insects, nematodes, and cultured mammalian cells. It caused 

base-pair gene mutations in Salmonella typhimurium and DNA adducts, DNA-protein crosslinks, DNA-DNA crosslinks, DNA singlestrand breaks, unscheduled DNA synthesis, inhibition of DNA repair, 

gene mutations, cell transformation, and cytogenetic effects (sister 

chromatid exchange, chromosomal aberrations, and micronucleus 

formation) in cultured mammalian cells (NTP 2010). It was also genotoxic in experimental animals and humans exposed in vivo (discussed 

below). There is some evidence to suggest that the Fanconi anemia 

complementation group (BRCA/FANC) response pathway may be 

important in the prevention of DNA damage from formaldehyde 

exposure (Zhang et al. 2010a). Cells deficient in FANC genes were 

hypersensitive to formaldehyde exposure and had increased frequencies of micronuclei and cancer (Speit et al. 2000, Ridpath et al. 2007).

Nasal Cancer 

Mechanistic studies in humans and experimental animals support 

the findings that formaldehyde causes nasopharyngeal and sinonasal cancer in humans. Formaldehyde causes genetic damage to the 

nasal tissues of both experimental animals and humans exposed by 

inhalation. DNA-protein crosslinks were detected in the nasal mucosa of rats exposed to formaldehyde (Casnaova et al. 1989, 1994, 

NTP 2010) and in the nasal turbinates (Heck et al. 1989, Casanova 

et al. 1991) and the respiratory tract (larynx, trachea, carina, and 

bronchi) (Casanova et al. 1991) of rhesus monkeys exposed to formaldehyde, which correspond to the observed tumor sites in humans 

(nasal and nasopharyngeal). In dose-response studies in rats, DNA 

crosslinks were correlated with tumor incidence (Liteplo and Meek 

2003). DNA-protein crosslinks were also correlated with the severity and anatomical location of proliferative nasal lesions in rhesus 

monkeys (Casanova et al. 1991). N2-hydroxmethyl-deoxyguanosine 

(dG) DNA monoadducts and dG-dG crosslinks were found in rat nasal mucosa (Lu et al. 2010). Mutations in the p53 tumor-suppressor 

gene (at G:C base pairs) were found in formaldehyde-induced nasal 

squamous-cell carcinomas in rats, and all of the identified codon mutations have also been found in human cancers (Recio et al. 1992). In 

humans, formaldehyde exposure was associated with higher levels of 

serum p53 protein (wild-type and mutant p53 protein), and serum 

p53 protein levels were positively correlated with mutant p53 protein 

levels. Higher levels of DNA-protein crosslinks in lymphocytes were 

significantly associated with increased risk of higher serum p53 levels 

(Shaham et al. 2003). However, p53 mutations were not observed in 

rat nasal mucosa exposed to formaldehyde for 13 weeks, suggesting 

that they may be a later event in the progression of cancer (Meng et 

al. 2010). Numerous studies of industrial workers and professional 

groups exposed to formaldehyde found that formaldehyde exposure 

increased the frequency of micronuclei in the nasal epithelium and 

buccal epithelium (Ballarin et al. 1992, Suruda et al. 1993, TitenkoHolland et al. 1996, Kitaeva et al. 1996, Ying et al. 1997, Burgaz et al.

2001, 2002, Ye et al. 2005). 

Inhalation-exposure studies in experimental animals have shown 

that airway deposition and cytotoxicity-induced cellular proliferation also are important factors in the carcinogenicity of formaldehyde to nasal cells. In rats, regional formaldehyde flux (as estimated 

by computational fluid dynamic models) was correlated with the anatomical distribution of formaldehyde-induced lesions (squamous 

metaplasia) (Kimbell et al. 1997) and DNA-protein crosslinks (Hubal et al. 1997). Inhalation of formaldehyde by rodents causes cytotoxicity of the respiratory epithelium (rhinitis, epithelial dysplasia, 

and squamous metaplasia) (Chang et al. 1983, Monticello et al. 1991, 

1996), which can result in cellular proliferation and the promotion of 

chemically induced or spontaneous mutations. Cellular proliferation 
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National Toxicology Program, Department of Health and Human Services

has been shown to be correlated with local nasal tumor incidence 

(Monticello et al. 1989, 1996). Formaldehyde exposure also causes 

cytotoxicity and cellular proliferation at anatomical sites that are not 

thought to be the origin of the squamous-cell carcinoma, suggesting 

that factors other than cellular proliferation play a role in formaldehyde-induced nasal cancers (Monticello et al. 1991).

Leukemia

Lymphohematopoietic cancers are a heterogeneous group of cancers 

that arise from damage to stem cells during hematopoietic and lymphoid development (Greaves 2004). Blood cells arise from a common 

stem cell, which forms two progenitor cells, the common myeloid 

stem cell and the common lymphoid stem cell. Most agents known to 

cause leukemia are thought to do so by directly damaging stem cells 

in the bone marrow. In order for a stem cell to become malignant, it 

must acquire genetic mutations and genomic instability (Zhang et al.

2010a). Because formaldehyde is highly reactive and rapidly metabolized, a key question is how it can reach the bone marrow or cause 

toxicity or genotoxicity at distal sites. The endogenous concentration in the blood of humans, monkeys, and rats is about 2 to 3 μg/g, 

and the concentration does not increase after inhalation of formaldehyde from exogenous sources (Heck et al. 1985, Casanova et al. 1988, 

Heck and Casanova et al. 2004). Moreover, N2-hydroxymethyl-dG–

DNA adducts have not been detected at distal sites in rats (such as 

the bone marrow, white blood cells, lung, spleen, liver, or thymus) 

(Lu et al. 2010). For these reasons, the plausibility of formaldehyde’s 

causing cancer at distal sites, such as myeloid leukemia, has been 

questioned (Golden et al. 2006, Pyatt et al. 2008). 

However, systemic effects have been observed after inhalation 

or oral exposure, and although the mechanisms by which formaldehyde causes myeloid leukemia in humans are not known, a number 

of plausible mechanisms have been advanced. These include (1) theoretical mechanisms for the distribution of formaldehyde to distal 

sites and (2) proposed mechanisms of leukemogenesis that do not 

require formaldehyde to reach the bone marrow. In addition, there 

is some evidence that formaldehyde causes adverse hematological 

effects in humans. 

Systemic Effects Observed After Inhalation or Oral Exposure

Serum levels of formaldehyde-albumin adducts were significantly 

higher in laboratory workers exposed to high levels of formaldehyde 

than in workers exposed at lower levels (Pala et al. 2008). In addition, levels of formaldehyde-DNA adducts in leukocytes were significantly higher in smokers than in nonsmokers; however, it is not 

known whether the source of the adducts was formaldehyde in tobacco smoke or from metabolism of a tobacco-specific compound 

(Wang et al. 2009). Numerous studies in humans and experimental animals have demonstrated that inhaled formaldehyde can cause 

toxicity, genotoxicity, and cancer at distal sites. In humans, formaldehyde exposure has been associated with (1) hematological toxicity 

(see below), (2) genotoxic damage in lymphocytes, including DNAprotein crosslinks, DNA strand breaks (Shaham et al. 2003, Costa et 

al. 2008), micronucleus formation (Suruda et al. 1993, He et al. 1998, 

Orsiére et al. 2006, Costa et al. 2008), and chromosomal aberrations 

(albeit not in all studies) (Jakab et al. 2010, NTP 2010), and (3) myeloid leukemia (discussed above).

In experimental animals, inhaled formaldehyde was associated 

with toxicity to the liver in several species (Beall and Ulsamer 1984, 

Cikmaz et al. 2010) and the nervous system (neurobehavioral changes 

and cellular and biochemical changes in the hippocampus) in mice 

and rats (Aslan et al. 2006, Sarsilmaz et al. 2007, Lu et al. 2008, Songur et al. 2010). In rats, it was also associated with toxicity to the testes (morphometric changes in the seminiferous epithelium) (Özen et 

al. 2005, Golalipour et al. 2007), spleen (morphometric alterations 

in the white pulp) (Golalipour et al. 2008), and thyroid gland (lower 

weight and changes in levels of thyroid hormones) (Patel et al. 2003). 

The mechanisms for systemic toxicity in experimental animals are 

not known, but oxidative stress has been suggested to play a role in 

testicular toxicity and neurotoxicity. In general, most studies did not 

present information on whether respiratory injury was observed with 

formaldehyde exposure.

Inhaled formaldehyde also caused DNA single-strand breaks in 

the liver and lymphocytes of male rats (Im et al. 2006), dominant lethal mutations in rats (Kitaeva et al. 1990), and heritable mutations 

in mice (Liu et al. 2009); however, most studies found no cytogenetic 

effects (NTP 2010). Findings for chromosomal aberrations in bone 

marrow of rats exposed to inhaled formaldehyde are conflicting; aberrations were found by Kitaeva et al. (1990), but not by Dallas et al.

(1992). Prenatal exposure of rats to formaldehyde by intraperitoneal 

injection caused DNA-protein crosslinks and DNA strand breaks in 

the fetal liver (Wang and Liu 2006), and oral exposure to formaldehyde caused testicular tumors (Soffritti et al. 2002). 

Theoretical Mechanisms for the Distribution of Formaldehyde 

to Distal Sites

The mechanisms by which formaldehyde causes toxicity at distal sites 

are unknown. The formation of methanediol (discussed above) from 

formaldehyde helps to explain how a reactive chemical could be distributed and undergo metabolism throughout the body (Fox 1985, 

Matubayasi et al. 2007). The upper respiratory tissues are covered by 

an aqueous mucous membrane, through which formaldehyde could 

be transported as methanediol (Georgieva et al. 2003). In addition, 

formaldehyde reacts reversibly with a variety of endogenous molecules, including glutathione, amino acids, and folic acid (Heck et al.

1982). These reversible products may be transported from the portal of entry to reach remote sites where free formaldehyde can then 

be released. However, there is no experimental evidence to support 

these potential mechanisms.

Other Potential Mechanisms of Formaldehyde-Induced Leukemia

Zhang et al. (2009) proposed that formaldehyde could also cause leukemia by other mechanisms that do not involve direct damage to the 

bone marrow: (1) formaldehyde could damage stem cells circulating 

in the blood, which travel to the bone and become initiated leukemia 

cells, or (2) it could damage stem cells that reside in the nasal turbinates or olfactory mucosa. Hematopoietic stem cells have been identified in the peripheral circulation and can circulate back to the bone 

marrow (Fritsch et al. 1996). The findings of cytogenetic damage in 

circulating lymphocytes of formaldehyde-exposed workers (discussed 

above) support the first hypothesis, and the findings of cytogenetic 

damage (micronuclei) in nasal tissue support the second. High levels of chromosomal aberrations and micronuclei are associated with 

increased cancer risks in otherwise healthy individuals (Bonassi et 

al. 2008, Murgia et al. 2008). Moreover, Murrell et al. (2005) found 

that the olfactory epithelium of the nasal passages of rats contained 

multipotent stem/progenitor cells that were able to repopulate the 

hematopoietic tissues of irradiated rats and to form progenitor cells 

of multiple lineages. 

Hematotoxicity 

Damage to hematopoietic stem or progenitor cells would result in adverse hematological effects, which have been reported in some, but 

not all, studies in humans. However, no adverse hematological effects 

have been reported in subchronic or chronic studies in experimental 
Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

animals (Dean et al. 1984, Appelman et al. 1988, Kamata et al. 1997). 

Zhang et al. (2010b) found that formaldehyde-exposed workers had 

lower counts of white blood cells, granulocytes, platelets, red blood 

cells, and lymphocytes than did non-exposed workers. Furthermore, 

myeloid progenitor cells cultured from the blood of a subset of workers showed an increased frequency of aneuploidy of chromosomes 7 

(monosomy) and 8 (trisomy). Monosomy 7 and trisomy 8 are associated with myeloid leukemia (Johnson and Cotter 1997, Paulsson and 

Johansson 2007). In addition, formaldehyde exposure in vitro caused a 

decrease in colony-forming progenitor cells (erythroid burst-forming 

units, erythroid colony-forming units, and granulocyte, erythrocyte, 

monocyte, and megakaryocyte colony-forming units). A review of the 

Chinese literature reported that decreased white blood cell counts 

were observed in most studies of formaldehyde-exposed workers; in 

the largest study, exposed workers had higher percentages of blood 

abnormalities (decreased white blood cell and platelet counts and 

abnormal hemoglobin levels) (Tang et al. 2009).

Properties

Formaldehyde is the simplest aldehyde. It exists at room temperature 

as a nearly colorless gas with a pungent, suffocating odor (ATSDR 

1999, HSDB 2009). It is soluble in water, ether, acetone, and benzene. 

The primary form of formaldehyde in dilute aqueous solutions is its 

monomeric hydrate methylene glycol (methanediol), and the primary forms in concentrated solutions are oligomers and polymers of 

polyoxymethylene glycols. Commercially, formaldehyde is most often available as 30% to 50% (by weight) aqueous solutions of the hydrated form, which is commonly referred to as formalin (IARC 2006). 

Formalin contains added stabilizers, generally up to 15% methanol or 

lower concentrations (usually several hundred milligrams per liter) 

of various amine derivatives. In the absence of stabilizers, formaldehyde in solution oxidizes slowly to form formic acid and polymerizes 

to form oligomers, including paraformaldehyde, a polymer with 8 to 

100 units of formaldehyde (HSDB 2009). Formaldehyde can also exist in solid form as 1,3,5-trioxane, a cyclic trimer. Formaldehyde gas 

is generally stable in the absence of water, but it is flammable and 

can be ignited by heat, sparks, or flame. Vapors form explosive mixtures with air. Formaldehyde gas reacts violently with strong oxidizing agents and with bases and reacts explosively with nitrogen dioxide 

at around 180°C (356°F) (Akron 2009). Physical and chemical properties of formaldehyde are listed in the following table. 

Property Information

Molecular weight 30.0a

Specific gravity 0.815 at –20°C/4°Cb

Melting point –92°Ca

Boiling point –19.5°Ca

Log Kow 0.35a

Water solubility 400 g/L at 25°Ca

Vapor pressure 3,890 mm Hg at 25°Ca

Vapor density relative to air 1.067a

Dissociation constant (pKa) 13.27 at 25°Ca

a

HSDB 2009, bO’Neil et al. 2006.

Use

Formaldehyde has numerous industrial and commercial uses; it is 

used in industrial processes primarily as a solution (formalin) or solid 

(paraformaldehyde or trioxane). The predominant use (~55% of total consumption) is in the production of industrial resins (mainly 

urea-formaldehyde, phenol-formaldehyde, polyacetal, and melamineformaldehyde resins) (Bizzari 2007). These resins are used to manufacture numerous commercial products, including adhesives and 

binders for composite wood products, pulp and paper products, plastics, and synthetic fibers, and in textile finishing. Another major use 

(~29%) is as a chemical intermediate to produce other chemicals. 

Various agricultural uses (~5%), paraformaldehyde production (~3%), 

and production of chelating agents (~3%) account for most of the remaining uses. The remaining 5% of formaldehyde goes toward other 

uses that may still be important for human exposure, including its use 

as a disinfectant or antimicrobial agent in various consumer products, 

as a medical treatment for some skin conditions, as a tissue preservative for pathologists and embalmers, and as a biocide and preservative in food and cosmetic products. Formaldehyde is registered as 

a materials preservative for use in consumer products such as laundry detergents, general-purpose cleaners, and wallpaper adhesives 

(ATSDR 1999, IARC 2006, EPA 2008). The main uses for paraformaldehyde are as foundry resins and in applications where the presence 

of water could interfere with a production process. Paraformaldehyde is also used as an antimicrobial agent for in-drawer fumigation 

of hair-cutting equipment and as a mildewcide in closets and unoccupied vacation homes (EPA 2008).

Production

Formaldehyde is produced by catalytic oxidation of methanol via a 

silver or metal-oxide catalyst process. Annual production of formaldehyde in the United States increased from about 0.9 million metric tons (1 million tons) in 1960 to 4.5 million metric tons (5 million 

tons) in 2006 (Bizzari 2007). In 2009, formaldehyde was produced by 

12 companies and their subsidiaries at 39 U.S. manufacturing plants 

(Bizzari 2007, SRI 2009), and paraformaldehyde and trioxane each 

were produced at one U.S. manufacturing plant (SRI 2009). Formaldehyde was available from 36 U.S. suppliers, paraformaldehyde from 

25, and trioxane from 11. Internationally, formaldehyde was available 

from 152 suppliers in 25 countries, paraformaldehyde from 59 in 15 

countries, and trioxane from 21 in 9 countries (ChemSources 2009). 

Because of transportation and storage issues associated with formaldehyde, it usually is produced close to the point of consumption; 

therefore, international trade in formaldehyde is minimal (less than 

2% of worldwide production) (Bizzari 2007). In 2006, U.S. imports of 

formaldehyde were about 10,000 metric tons (11,000 tons), and U.S. 

exports were about 14,000 metric tons (15,400 tons).

Exposure

Humans are exposed to formaldehyde in the environment and in the 

workplace. Formaldehyde concentrations in the environment generally are reported in parts per billion, but exposure levels are much 

higher in the workplace, occurring in the range of parts per million. 

Formaldehyde is also produced endogenously in humans and animals. 

Environmental Exposure

Formaldehyde is ubiquitous in the environment and has been detected 

in indoor and outdoor air, soil, food, treated and bottled drinking water, surface water, and groundwater (NTP 2010). The general population can be exposed to formaldehyde primarily from breathing indoor 

or outdoor air, from tobacco smoke, from use of cosmetic products 

containing formaldehyde, and, to a more limited extent, from ingestion of food and water. For the general population, the major sources 

of airborne formaldehyde exposure include combustion sources, offgassing from numerous construction and home-furnishing products, 

and offgassing from consumer goods. Formaldehyde gas is produced 

from the oxidation or incomplete combustion of organic material. 

Combustion sources include automobiles and other internal combustion engines, power plants, incinerators, refineries, forest fires, 

wood stoves, and cigarettes. Formaldehyde is also formed in the early 

stages of decomposition of plant residues in soil (IARC 2006). Form-
Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

aldehyde can be produced secondarily in air via photochemical reactions involving virtually all classes of hydrocarbon pollutants; in 

some instances, secondary production may exceed direct air emissions. Formaldehyde concentrations in outdoor air generally range 

from 0 to 100 ppb (0 to 0.1 ppm) and usually are less than 10 ppb 

(0.01 ppm); daily exposure from outdoor air has been estimated at 

0.1 mg or less (HSDB 2009).

Formaldehyde levels can be higher in indoor air than in outdoor 

air. Important determinants of indoor air levels include the sources 

of the formaldehyde, the age of the source materials, temperature, 

humidity, and ventilation rates (IARC 2006). Although daily formaldehyde exposure from residential indoor air in conventional homes 

has been reported to range from 0.5 to 2.0 mg, daily exposure in a 

prefabricated home was as high as 10 mg (Fishbein 1992). Temporary 

housing provided by the Federal Emergency Management Agency as 

shelter for residents of Louisiana and Mississippi displaced by Hurricanes Katrina and Rita had formaldehyde concentrations ranging 

from 3 to 590 ppb (0.003 to 0.59 ppm) (CDC 2008, 2009). Most of the 

housing was at least two years old at the time of sampling, which occurred during the winter months. Formaldehyde levels were higher 

in travel trailers than park models or mobile homes. Higher concentrations of formaldehyde than were found by the Centers for Disease 

Control and Prevention have been reported by others (for example, 

see COGR 2007). There are no federal guidelines for formaldehyde 

levels in residential housing for indoor air quality (CDC 2008).

Daily exposure to formaldehyde was estimated at up to 2 mg from 

smoking 20 cigarettes per day, up to 3.5 mg from environmental tobacco smoke in the home, and 2.8 mg from environmental tobacco 

smoke in the workplace (WHO 2000). 

The general population could also be exposed to formaldehyde by 

handling consumer products that contain formaldehyde as an antimicrobial agent (such as laundry detergents, wallpaper adhesive, or 

sanitizers) or from its use as a mildewcide for clothing and linens or 

in vacation homes (EPA 2008). Although formaldehyde per se now is 

rarely used in cosmetics, the use of formaldehyde releasers is common. 

An analysis of data from the U.S. Food and Drug Administration’s 

Voluntary Cosmetic Registration Program Database indicated that 

nearly 20% (6,463 of 33,212) of cosmetic products contained formaldehyde (including formalin) or any of eight formaldehyde-releasing 

preservatives (benzylhemiformal, 5-bromo-5-nitro-1,3-dioxane, 

2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, 1,3-dimethylol5,5-dimethylhydantoin, imidazolidinyl urea, quaternium-15, or sodium hydroxymethylglycinate) (De Groot and Veenstra 2010, De 

Groot et al. 2010). Absorption of formaldehyde from hand cream 

or suntan lotion was estimated at up to 0.1 mg for a typical application, assuming 5% absorption through the skin (ATSDR 1999). Other 

products that often contain formaldehyde releasers are industrial and 

household cleaning agents, soaps, shampoos, paints, lacquers, and 

cutting fluids (WHO 2002).

Food and water contain measureable concentrations of formaldehyde (WHO 2002, Mutsuga et al. 2006), but the significance of ingestion as a source of formaldehyde exposure for the general population 

is questionable. Formaldehyde in food exists mostly in a bound form 

(IPCS 1989, Fishbein 1992), and it is considered to be unstable in 

aqueous solution (ATSDR 1999). Formaldehyde present in food can 

occur naturally or through inadvertent contamination; it can also be 

added as a preservative, disinfectant, or bacteriostatic agent and can 

result from cooking or smoking of foods (Howard 1989, IPCS 1989, 

ATSDR 1999). Generally, higher levels were reported in fish, seafood, and smoked ham than in other foods (Li et al. 2007, NTP 2010). 

Formaldehyde in treated drinking water occurs primarily through the 

oxidation of organic matter during ozonation or chlorination; concentrations of up to 30 μg/L were reported (WHO 2005). Formaldehyde can also be present in the water before treatment; it was found 

in 16 of 35 influent samples at concentrations ranging from 1.2 to 

13 μg/L (Krasner et al. 1989).

Formaldehyde is an essential metabolic intermediate in the biosynthesis of purines, thymidine, and some amino acids. It is also 

produced via metabolism of some amino acids and a variety of xenobiotics, such as drugs, food additives, and other environmental chemicals (IARC 2006). The endogenous concentration of formaldehyde in 

the blood of humans, monkeys, and rats is approximately 2 to 3 μg/g 

(Heck et al. 1985, Casanova et al. 1988). 

Occupational Exposure

In occupational environments, formaldehyde occurs mainly as a gas; 

however, formaldehyde particulates can be inhaled when paraformaldehyde or powdered resins are used or when formaldehyde adsorbs 

to other particles, such as wood dust (IARC 1995). Workers may 

also be exposed through contact of formalin solutions or liquid resins with the skin or eyes. Occupational exposure to formaldehyde is 

highly variable and can occur in numerous industries, including the 

manufacture of formaldehyde and formaldehyde-based resins, woodcomposite and furniture production, plastics production, embalming, 

foundry operations, fiberglass production, construction, agriculture, 

firefighting, and histology, pathology, and biology laboratories, among 

others. In the past, the highest continuous exposure levels were measured during the varnishing of furniture and wooden floors, during 

the finishing of textiles, in the garment industry, during the treatment 

of furs, and in certain jobs in manufactured board mills and foundries. Short-term exposure to high levels of formaldehyde has been 

reported for embalmers, pathologists, and paper workers. Lower levels of exposure have usually been reported for the manufacture of 

synthetic vitreous fibers, abrasives, and rubber, and in formaldehyde 

production (IARC 2006). It has been suggested that because formaldehyde is ubiquitous, occupational exposure occurs in all workplaces 

(WHO 2002). Daily formaldehyde intake from occupational exposure 

has been estimated at up to 8 mg (WHO 2000). 

In the United States, high exposure levels were reported for 

formaldehyde-based resin production (mean concentrations of up 

to 14.2 ppm), plastic product production (up to 38.2 ppm) (Stewart 

et al. 1987), embalming (up to 2.6 ppm) (Stewart et al. 1992), biology teaching laboratories (up to 8.3 ppm) (EPA 1981), and pathology 

autopsy laboratories (up to 4.35 ppm) (Moseley et al. 1979). Using 

formaldehyde exposure data from the Occupational Safety and Health 

Administration (OSHA) air sampling database for various U.S. industries from 1979 to 2001, Lavoué et al. (2008) found the highest estimated relative indices of exposure based on time-weighted-average 

exposure data for the reconstituted wood products and lumber and 

wood products industries. The highest estimated relative indices of 

exposure based on short-term exposure data (aggregated short-term, 

peak, and ceiling exposure levels) were for the reconstituted wood 

products industry and funeral services and crematories.

In the late 1980s, OSHA estimated that over 2 million U.S. workers were exposed to formaldehyde, about 45% of whom worked in 

the garment industry (USDL 2009). OSHA estimated that about 1.9 

million workers were exposed to formaldehyde at concentrations between 0.1 and 0.5 ppm, 123,000 at 0.5 to 0.75 ppm, and 84,000 at 0.75 

to 1 ppm (WHO 2002). No current data were found for occupational 

exposure to formaldehyde in the United States.
Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

Regulations

Coast Guard, Department of Homeland Security

46 CFR 150 and 151 detail procedures for shipping formaldehyde, formaldehyde solution, and 

1,3,5-trioxane with incompatible chemicals.

Minimum requirements have been established for safe transport of formaldehyde solutions on ships 

and barges.

Consumer Product Safety Commission (CPSC)

Formaldehyde and products containing 1% or more formaldehyde are considered “strong sensitizers” 

and must display a warning label.

Department of Agriculture (USDA)

Limits have been established for the amount of residual formaldehyde in inactivated bacterial products 

and killed-virus vaccines.

Department of Housing and Urban Development (HUD)

All plywood and particleboard materials bonded with a resin system or coated with a surface finish 

containing formaldehyde shall not exceed the following emission levels when installed in 

manufactured homes: 0.2 ppm for plywood and 0.3 ppm for particleboard.

Manufactured homes must prominently display a notice which provides information on formaldehyde 

sources, levels, health effects, and remedial actions to reduce indoor levels.

Department of Transportation (DOT)

Formaldehyde, formalin, and paraformaldehyde are considered hazardous materials, and special 

requirements have been set for marking, labeling, and transporting these materials, as prescribed 

in 49 CFR 172.

Environmental Protection Agency (EPA)

Clean Air Act

Clean-Fuel Vehicles: Formaldehyde emissions limits have been established for various classes of cleanfuel vehicles.

Control of Emissions from New and In-Use Highway Vehicles and Engines: Formaldehyde emissions limits 

have been established for various classes of vehicles.

Mobile Source Air Toxics: Listed as a mobile source air toxic for which regulations are to be developed.

National Emissions Standards for Hazardous Air Pollutants: Listed as a hazardous air pollutant.

New Source Performance Standards: Manufacture of formaldehyde is subject to certain provisions for 

the control of volatile organic compound emissions.

Prevention of Accidental Release: Threshold quantity (TQ) = 15,000 lb.

Regulation of Fuels and Fuel Additives: Under reformulated gasoline certification requirements, 

formaldehyde emissions levels must not be exceeded.

Urban Air Toxics Strategy: Identified as one of 33 hazardous air pollutants that present the greatest 

threat to public health in urban areas.

Clean Water Act

Formaldehyde and paraformaldehyde are listed as hazardous substances.

Comprehensive Environmental Response, Compensation, and Liability Act

Formaldehyde reportable quantity (RQ) = 100 lb.

Paraformaldehyde reportable quantity (RQ) = 1,000 lb.

Emergency Planning and Community Right-To-Know Act

Toxics Release Inventory: Listed substance subject to reporting requirements.

Reportable quantity (RQ) = 100 lb.

Threshold planning quantity (TPQ) = 500 lb.

Resource Conservation and Recovery Act

Listed Hazardous Waste: Waste codes for which the listing is based wholly or partly on the presence of 

formaldehyde = U122, K009, K010, K038, K040, K156, K157.

Listed as a hazardous constituent of waste.

Food and Drug Administration (FDA)

Numerous formaldehyde-based chemicals may be used as components of adhesives and coatings in 

packaging, transporting, or holding food provided that conditions prescribed in 21 CFR 175 are 

met.

Numerous formaldehyde-based chemicals may be safely used as articles intended for use in contact 

with food provided that conditions prescribed in 21 CFR 177 are met.

Numerous formaldehyde-based chemicals may be used in the production of paper products intended 

for use in producing, processing, preparing, treating, packaging, transporting, or holding food 

provided that conditions prescribed in 21 CFR 176 are met.

Formaldehyde and formaldehyde-based chemicals may be used as adjuvants, production aids, and 

sanitizers that come in contact with foods provided that conditions prescribed in 21 CFR 178 are 

met.

Formaldehyde-based ion-exchange resins may be used in the treatment of food provided that 

conditions prescribed in 21 CFR 173 are met.

Formaldehyde may be safely used in the manufacture of animal feeds in accordance with conditions 

prescribed in 21 CFR 573.460.

Formalin, containing approximately 37% formaldehyde gas by weight, can be used in environmental 

waters for the control of fungi and parasites for certain finfish and shellfish as prescribed in 

21 CFR 529.

Mine Safety and Health Administration

Engine exhaust from mobile diesel-powered transportation equipment must be diluted with air so 

that the mixture contains no more than 0.001% by volume of aldehydes, calculated as equivalent 

formaldehyde.

Occupational Safety and Health Administration (OSHA)

While this section accurately identifies OSHA’s legally enforceable PELs for this substance in 2010, 

specific PELs may not reflect the more current studies and may not adequately protect workers.

Permissible exposure limit (PEL) = 0.75 ppm (0.92 mg/m3) (8-h TWA).

Short-term exposure limit (STEL) = 2ppm (2.46 mg/m3) (15-min exposure).

Action level = 0.5ppm (0.61 mg/m3) (8-h TWA).

Comprehensive standards have been developed for occupational exposure to formaldehyde gas, its 

solutions, and materials that release formaldehyde. These standards identify the permissible 

exposure limits and prescribe requirements for monitoring exposures, using respiratory protection, 

conducting medical evaluations, housekeeping, and other activities at 29 CFR 1910.1048 (General 

Industry), 29 CFR 1926.1148 (Construction Industry), and 29 CFR 1915.1048 (Shipyards).

Requirements for preventing or minimizing the consequences of catastrophic releases of toxic, reactive, 

flammable, or explosive chemicals are prescribed in 29 CFR 1910.119; the threshold quantity (TQ) 

for formaldehyde is 1,000 lb.

Guidelines

American Conference of Governmental Industrial Hygienists (ACGIH)

Threshold limit value – ceiling (TLV-C) = 0.3 ppm (0.37 mg/m3).

Listed as a suspected human carcinogen.

National Institute for Occupational Safety and Health (NIOSH)

Recommended exposure limit (REL) = 0.016 ppm (0.02 mg/m3) (10-h TWA).

Immediately dangerous to life and health (IDLH) limit = 20 ppm (24.56 mg/m3).

Ceiling recommended exposure limit = 0.1 ppm (0.12 mg/m3) (15-min exposure).

Listed as a potential occupational carcinogen.

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