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National Research Council (US) Committee on Toxicology. Formaldehyde - An Assessment of Its Health Effects. Washington (DC): National Academies Press (US); 1980.

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Formaldehyde - An Assessment of Its Health Effects.

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Several controlled-exposure studies have provided valuable dose-response data on the irritant effects of airborne formaldehyde. The information from these studies on the percentages of the exposed populations responding at various formaldehyde concentrations is summarized in Tables 4 and 5.

Sixteen healthy young subjects were exposed to formaldehyde at 0.25 0.42, 0.83, or 1.6 ppm 5 h/d for 4 d (Andersen, 1979). Measures of physiologic parameters, subjective discomfort, and mathematical performance were made in the control period and after 1–3 and 3–5 h of exposure. No significant changes were observed in pulmonary function, nor was there any difference in performance of mathematical tests between the control period and exposure to formaldehyde. The nasal-mucus flow rate was decreased at all concentrations except 0.83 ppm; the effect was observed only in the upper third of the nose. When asked about their subjective response to formaldehyde, subjects exposed at the four increasing formaldehyde concentrations reported “slight discomfort” averaging 9, 5, 11, and 18, respectively, on a scale of zero to 100. Specifically, the subjects complained of conjunctival irritation and dryness of the nose and throat.

In a second study, 33 subjects (24 men and 9 women) were exposed to formaldehyde at 0.03–3.2 ppm for a total of 35 min, and 48 others (35 men and 13 women) were exposed at 0.03–4 ppm for 1.5 min (Weber-Tschopp et al., 1977). Several responses were measured, such as eye, nose, and throat irritation, odor, “desire to leave the room,” and eye-blinking rate. An approximately linear relationship was found for the average responses over the range of concentrations. At 0.03 ppm, there was no difference in the average response between exposure to formaldehyde and control air. Significant changes began to appear at 1.2 ppm. The thresholds for the specific responses (shown in Table 5) ranged from 1.2 to 2.1 ppm. There was some suggestion of adaptation to the irritating effects of formaldehyde: at the same concentrations, responses to 1.5–min exposures were generally greater than the responses during 35–min exposures.

The eye-irritation response to exposures to formaldehyde for 5 min at 0.01 to 1.0 ppm was investigated in 12 subjects (Schuck et al., 1966). Subjective eye irritation was scored on a scale of zero to 24. Between 0.3 and 1.0 ppm, there was a linear increase in the average reported eye-irritation response, ranging from light irritation (just noticeable) to severe irritation. At concentrations below 0.3 ppm, a linear relationship was not found. Subjects experienced similar light irritation and eye-blinking rates at 0.05 ppm as they did at 0.5 ppm. The range of sensitivity to formaldehyde was evident by comparing the effects in two subjects. At 0.8 ppm, one reported barely noticeable irritation, while a second had severe irritation, including lacrimation. A complicating factor in this study was that, because of the method for generating formaldehyde, peroxyacetyl nitrate, nitrogen dioxide, and ethylene were present in the chamber.


Acute ingestion of formalin by humans has resulted in loss of consciousness, vascular collapse, pneumonia, hemorrhagic nephritis, and abortion. Formaldehyde has occasionally injured the larnyx and trachea, but damage to the gastrointestinal tract occurred primarily in the stomach and lower esophagus. Fatalities have resulted from ingestion of as little as 30 ml of formalin (Bohmer, 1934; Kline, 1925). The use of formaldehyde to devitalize dental pulp has produced paresthesia, soft-tissue necrosis, and sequestration of bone (Grossman, 1978; Heling et al., 1977; Montgomery, 1976). Filters impregnated with melamine-formaldehyde resin were associated with an outbreak of hemolytic anemia among hemodialysis patients (Orringer and Mattern, 1976).


Contact of the skin with formaldehyde may cause primary irritation or allergic dermatitis (Glass, 1961; Pirila and Kilpio, 1949). Rostenberg et al. (1952) reported eczematous sensitivity to formalin in nurses who handled thermometers that had been immersed in a 10% solution of formaldehyde. A similar outbreak occurred in a hemodialysis unit where a 2% formalin solution was used to sterilize open tanks (Blejer and Miller, 1966). Dermatitis has been reported after contact with nail-hardeners, textiles, resins, and gaseous formaldehyde (Engle and Calnan, 1966; Fisher et al., 1962; Lazar, 1966; Logan and Perry, 1973; O'Quinn and Kennedy, 1965). Allergy to formaldehyde resins may be the result of unreacted formaldehyde or formaldehyde arising from decomposition, other resin ingredients, or the resin itself (USDHEW, 1976a). The human data must be divided between two eras: earlier studies when 5% formaldehyde (in water) was the standard diagnostic concentration; and recent studies with 2% (in water) (Epstein and Maibach, 1966). The 5% formaldehyde concentration was unusually high for diagnostic purposes; even the 2% concentration is near the generally-accepted irritancy threshold, so these results also provide a sensitization rate much greater than would be expected for the general population. (North American Contact Dermatitis Group, 1973).

Formaldehyde has been shown to be a potent experimental allergen in humans. Skin sensitization was produced in about 8% of male subjects given repeated occlusive applications of 5 or 10% aqueous formaldehyde for 3.5 wk and then challenged with a 1% application 2 wk later (Marzulli and Maibach, 1973). Approximately 4% of 1,200 dermatology patients exhibited positive skin reactions when tested with 2% formalin (0.8% formaldehyde) under an occlusive patch (Rudner et al., 1973). Experiments suggest that most sensitized subjects can tolerate exposure to aqueous formaldehyde at 30 ppm (0.003%), applied to the axilla (Jordan et al., 1979; Maibach and Franz, [1980]). Sensitized subjects who tolerate formaldehyde-containing products may react to occludedpatch tests at lower concentrations; Marzulli and Maibach (1973) reported that 1/5 sensitized subjects reacted at a challenge concentration as low as 0.01%.

Although formaldehyde is a potent experimental allergen in man and animals, many of the daily exposures to formaldehyde (in shampoos, clothing, etc.) may involve quantities below the threshold for sensitization induction and elicitation or contact times less than that required to produce a response (Marzulli and Maibach, 1977). More complete quantitative induction and elicitation studies combined with provocative use tests should allow more realistic risk assessments.

Contact urticaria also occurs with formaldehyde (Odom and Maibach, 1977); however, epidemiologic data are not available, nor has the mechanism (type A, B or C) been identified.


Formaldehyde acts as a mucous-membrane irritant to cause conjunctivitis and lacrimation. Eye irritation is a common complaint and has been reported at airborne concentrations of 0.3–0.9 ppm in industrial workers (Bourne and Seferian, 1959; Morrill, 1961). Severe eye irritation can develop in the range of 4–20 ppm (Barnes and Speicher, 1942; Walker, 1964). Controlled human exposures indicated that the group threshold for eye irritation was 1.2 ppm, and for eye-blinking rate was 1.7 ppm (Weber-Tschopp et al., 1977). The eye blinking rate was doubled in 33% of the subjects exposed at 2.1 ppm and in 11% of those exposed at 0.5 ppm. A linear relationship was found for eye irritation in exposed subjects, from a group response of no irritation at 0.03 ppm to some irritation at 3.2 ppm. Tolerance to eye irritation was reported after exposure at 13.8 ppm for 10 min (Sim and Pattle, 1957). A complete visual-test battery and ophthalmologic examination of workers exposed at 1.5 ppm revealed no effects of formaldehyde on the eyes (USDHEW, 1976b). However, Schuck et al. (1966) found a linear relationship between eye irritation and formaldehyde concentration over a range of 0.3–1 ppm; these responses ranged from light to severe irritation. The authors determined that formaldehyde and peroxyacetyl nitrate accounted for 80% and 20%, respectively, of the eye irritation associated with photochemical air pollution.

Respiratory System

Formaldehyde has been reported to cause irritation and dryness of the nose and throat and olfactory fatigue. Upper airway irritation attributed to formaldehyde at 1–11 ppm occurred in employees handling nylon fabric coated with urea-formaldehyde resin (Ettinger and Jeremias, 1955). Customers in dress shops have complained of burning and stinging of the eyes, headaches, and nose and throat irritation with formaldehyde at 0.13–0.45 ppm (Bourne and Seferian, 1959). Similar complaints, along with disturbed sleep and unusual thirst, were reported by workers at a paper-conditioning installation (Morrill, 1961). Airborne formaldehyde concentrations released from paper treated with urea-formaldehyde or melamine-formaldehyde resin were found to be 0.9–1.6 ppm. Annoying odor, constant prickling irritation of mucous membranes, wheezing, tearing, excessive thirst, and disturbed sleep were reported by employees in eight textile plants (Shipkovitz, 1968). The prevalence of respiratory illness and complaints was more than 15% in four plants and 5–15% in the other four. Airborne formaldehyde was measured at 0–2.7 ppm, with an average of 0.68 ppm. Workers in a garment factory were examined by the California Department of Public Health; airborne concentrations ranged from 0.9–2.7 ppm (Blejer and Miller, 1966). Employees reported increased eye and upper respiratory tract irritation in areas where large quantities of partially completed permanent-press fabrics accumulated. Olfactory adaptation to the irritant effects of formaldehyde occurred within 30 min of exposure, but after a 1– to 2–h interruption of exposure irritation returned (Blejer and Miller, 1966; Kerfoot and Mooney, 1975; Shipkovitz, 1968).

Kerfoot and Mooney (1975) surveyed six funeral homes that used formaldehyde and paraformaldehyde in the embalming process. The average airborne concentrations in the embalming rooms were 0.25–1.39 ppm. The investigations noted eye and upper respiratory tract irritation in some employees.

A cross-sectional study of rubber workers exposed to a hexamethylene-tetramine-resorcinol resin revealed significant decreases in small airway function over the course of the workshift and an excess of symptoms such as chest tightness, eye and nose irritation, and cough (Gamble et al., 1976). No difference was found in baseline lung function tests between exposed and control groups. Chemical analysis of respirable particles was not performed and no association was found between airborne levels of resorcinol, formaldehyde, hydrogen cyanide, or ammonia and changes in pulmonary function. A study of employees producing filters with phenol-formaldehyde impregnated fibers indicated that pulmonary function (FEV1.0/FVC and MEF50%/FVC) measured at the beginning of the Monday shift was significantly lower in employees who had worked more than 5 yr compared to those never involved in production (Shoenberg and Mitchell, 1975). Chronic symptoms—chronic cough and excess phlegm—were increased in the group currently involved in production. Acute symptoms included eye, nose, and throat irritation and cough; however, little change was observed in the employees' FVC, FEV1.0, and MEF50% during the course of a workweek or workday. Formaldehyde was not systematically measured, but two surveys reported concentrations of 0.4–0.8 ppm and 9.14 ppm. The latter was thought to be atypical of the usual exposure conditions in the plant. Other pulmonary irritants present in the work environment included phenol and acrylic-fiber breakdown products.

Lower airway irritation may be evidenced by cough, chest tightness, and wheezing. One man developed dyspnea and asthma after acute inhalation of formalin vapor (Zannini and Russo, 1957). Clinical examination revealed pulmonary edema with a 40% decrease in vital capacity. A neurology resident developed actue respiratory distress after 15 h of exposure to formaldehyde (Porter, 1975). Auscultation of the chest revealed diffuse rales and occasional rhonchi. Chest x-ray revealed early pulmonary edema. The resident was known to have marked atopy to a wide range of allergens. Pulmonary edema, pneumonitis, and death may occur after inhalation of formaldehyde at concentrations exceeding 50 ppm (Fassett, 1963).

Nervous System

Olfactory fatigue with increased olfactory thresholds to rosemary, thymol, camphor, and tar were observed among plywood and particleboard workers (Weger, 1927; Yefremov, 1970). Numerous nonspecific symptoms related to nervous system response have been mentioned. Formaldehyde from resins used in construction produced thirst, headaches, dizziness, apathy, and inability to concentrate (Helwig, 1977). Workers exposed to phenol-formaldehyde resins complained of headaches, dizziness, disturbed sleep, weakness, and apathy (Weger, 1927). Studies in the USSR showed no electroencephalographic (EEG) changes in five subjects exposed to formaldehyde at 0.03 ppm, but these subjects did respond with EEG changes at 0.044 ppm (Fel'dman and Bonashevskaya, 1971).

Copyright © National Academy of Sciences.
Bookshelf ID: NBK217652


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