Formaldehyde Regulation and Related Disorders

Health related information on formaldehyde

Provided by BFGC Health Committee, Inae Lee, February 2011

Nasopharyngeal cancer

The relationship between nasopharyngeal cancer and exposure to formaldehyde has been investigated in seven case–control studies, five of which found elevated risks for overall exposure to formaldehyde or in higher exposure categories, including one in which the increase in risk was statistically significant.

The most recent meta-analysis, which was published in 1997, found an increased overall meta-relative risk for nasopharyngeal cancer.

Leukemia

Excess mortality from leukemia has been observed relatively consistently in six of seven studies of professional workers (i.e. embalmers, funeral parlor workers, pathologists and anatomists). A recently published meta-analysis of exposure to formaldehyde among professionals and the risk for leukemia reported increased overall summary relative risk estimates for embalmers, and for pathologists and anatomists, which did not vary significantly between studies (i.e. the results were found to be homogeneous).

The updated study of British industrial workers failed to demonstrate excess mortality among workers exposed to formaldehyde. The lack of positive findings in this study is difficult to reconcile with the findings from the studies of garment workers and industrial workers in the USA and studies of professionals.

In summary, there is strong but not sufficient evidence for a causal association between leukemia and occupational exposure to formaldehyde. Increased risk for leukemia has consistently been observed in studies of professional workers and in two of three of the most relevant studies of industrial workers. These findings fall slightly short of being fully persuasive because they conflict with the non-positive findings from the British cohort of industrial workers.

Cancer at other sites

A number of studies have found associations between exposure to formaldehyde and cancer at other sites, including the oral cavity, oro- and hypopharynx, pancreas, larynx, lung and brain. However, the Working Group considered that the overall balance of epidemiological evidence did not support a causal role for formaldehyde in relation to these other cancers.

Toxic effects in humans

Many studies have evaluated the health effects of inhalation of formaldehyde in humans. Most were carried out in un-sensitized subjects and revealed consistent evidence of irritation of the eyes, nose and throat. Symptoms are rare below 0.5 ppm, and become increasingly prevalent in studies in exposure chambers as concentrations increase. Exposures to up to 3 ppm [3.7 mg/m3] formaldehyde are unlikely to provoke asthma in an un-sensitized individual. Bronchial provocation tests have confirmed the occurrence of occupational asthma due to formaldehyde in small numbers of workers from several centers. The mechanism is probably hypersensitivity, because the reactions are often delayed, there is a latent period of symptomless exposure and unexposed asthmatics do not react to the same concentrations. High levels of formaldehyde probably cause asthmatic reactions by an irritant mechanism. Formaldehyde is one of the commoner causes of contact dermatitis and is thought to act as a sensitizer on the skin

Evaluation

Formaldehyde is proven to be carcinogenic to humans. An increased risk for nasopharyngeal cancer was found and there is strong indication for a causal association between leukemia and occupational exposure to formaldehyde.

There is consistent evidence of irritation of the eyes, nose and throat. High levels of formaldehyde probably cause asthmatic reactions by an irritant mechanism.

The reactions are often delayed; there is a latent period of symptomless exposure, before asthma is provoked. Formaldehyde causes contact dermatitis and is thought to act as a sensitizer on the skin.

Interpretation Standards

On an international level there is a confusingly wide span of maximum contaminant levels (MCL) set in various countries.

Example: occupational formaldehyde exposure standards in selected countries [i]

 

Country	Concentration in mg/m³ [ppm]	Interpretation
High standard
Belgium, Hong Kong, Malaysia Spain	0.37   [0.3] 0.37   [0.3]	Ceiling STEL a
Medium standard
New Zealand	1.2     [1.0]	Ceiling
Low standard
United Kingdom	2.5     [2.0] 2.5     [2.0]	STEL TWA b

a … STEL: short-term exposure limit

b … TWA: time-weighted average

 

There are different occupational guidelines even within one country:

 

Country, Region, Agency	Concentration in mg/m³ [ppm]	Interpretation
USA
ACGIH (TLV) c NIOSH (REL) d   OSHA (PEL) e	0.37   [0.3] 0.02   [0.016] 0.12   [0.1] 0.9     [0.75] 2.5     [2.0]	Ceiling TWA Ceiling TWA STEL
Canada
Alberta and Quebec Ontario	1.2     [1.0] 0.37   [0.3]	Ceiling Ceiling

c … ACGIH: American Conference of Governmental Industrial Hygienists, TLV: Threshold Limit Value

d … NIOSH: The National Institute for Occupational Safety and Health, REL: Recommended Exposure Limit

e … OSHA: Occupational Safety and Health Administration, PEL: Permissible Exposure Limit

 

Defining exposure limits for certain settings, purposes and groups of people is a partly subjective act. In order to interpret the numbers announced by the various agencies or organizations the following questions must be looked into:

• What interest does the institution pursue?
• Who provides funding for the institution or the activities leading to the finding of exposure limits?
• For which group of people and for what purpose is a particular number or set of numbers recommended?
• What kinds of studies have been conducted or what existing studies have served as reference for the definition of a certain number?
• Normal ambient air concentration:
  < 0.01 mg/m³ … general
  0.02 mg/m³ … in highly urbanized or industrial areas
• Normal mean indoor air concentration in homes[ii]:
  < 0.05 mg/m³
• Normal mean indoor air concentration in public and office buildings:
  < 0.03 mg/m³
• Allowed maximum of mean indoor air concentration in manufactured houses
  (mobile homes, trailers):
  < 0.2 mg/m³ (0.4 ppm)
• Normal elevated air concentration in new or recently renovated buildings, in new furnishings, or at hot and humid seasons (short-term exposure):
  > 0.2 mg/m³ (0.4 ppm)
• Exposure limits critical for health effects:
  0.2 – 0.4 mg/m³ … odor threshold[iii]
  0.38 mg/m³ … lowest concentration causing subjective (self-reported) sensory irritation of the eyes in humans for four hours
  0.63 mg/m³ … lowest concentration causing trigeminal stimulation of the eyes, e.g. increased eye blink frequency and conjunctival redness, for four hours (objective sensory irritation of the eyes) – also considered by the WHO as the NOAEL[iv] for objective eye irritation
• Possible life time exposure limit that is expected not to cause any adverse effects according to the US EPA:
  1.2 mg/m³ (1 ppm) … This value is discussed controversially.[v]
• Occupational exposure limit determined by the OSHA, PEL[vi]:
  0.9 mg/m³  (0.75 ppm) – TWA (time-weighted average) for 8-hour workdays
  2.5 mg/m³ (2 ppm) – STEL (short-term exposure limit) for 15 minutes

Basic benchmarks of formaldehyde air concentration