FORMALDEHYDE

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) BFV
2) Dormol
3) FANNOFORM
4) FORMALDEHYDE, GAS
5) FORMALITH
6) FORMIC ALDEHYDE
7) FYDE
8) IVALON
9) LYSOFORM
10) METHANAL
11) METHYL ALDEHYDE
12) METHYLENE OXIDE
13) MORBICID
14) OXOMETHANE
15) OXYMETHYLENE
16) Pesticide Code: 043001
17) SUPERLYSOFORM

1.2.1) MOLECULAR FORMULA
1) C-H2-O
2) HCHO

Available Forms Sources

1) Pure formaldehyde is not sold commercially due to its tendency to polymerize. It is most commonly available as formalin, an aqueous solutions containing from 37% to 56% formaldehyde, by weight, with varying amounts of methanol as a stabilizer (usually 10% to 15%). Other inhibitors of polymerization used with formaldehyde include: ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, and isophthalobisguanamine (Bingham et al, 2001; NFPA, 2002a).
2) Formaldehyde is also available as a solid polymer, paraformaldehyde (CAS 9002-81-7) in a powder or flaked form containing from 90 to 93% formaldehyde, and as its cyclic trimer, trioxane (CAS 123-63-7) (Bingham et al, 2001).

1) Formaldehyde is manufactured from methanol and air through a process using a metal or metal oxide catalyst ((HSDB, 2002)).
2) Formaldehyde gas may be emitted from fiberboard in cabinets or furniture, shelving, wall panels, or sub-flooring. Burning wood, cigarette smoking, and other forms of incomplete combustion emit formaldehyde (NSC , 2002).

1) INDUSTRIAL/HOUSEHOLD

a) Formaldehyde is used in fertilizers, insecticides, germicides, fungicides, herbicides, sewage treatment, paper-making, preservatives, embalming fluids, disinfectants, urea-formaldehyde resins, foam insulation, industrial and soil sterilants, urea and melamine resins, polyacetal and phenolic resins, artificial silk and cellulose esters, dye fasteners, explosives, latex-backed fabrics, particle board, plywood, air fresheners, cosmetics, wet fingernail hardeners and polishes, antimicrobial hair shampoos and conditioners, water-based paints, tanning and preserving hides, and as a chemical intermediate (ACGIH, 1991; Bingham et al, 2001; Budavari, 1996; Lewis, 1998; Sainio et al, 1997; Turoski, 1985).
b) Additional uses of formaldehyde include: production of ethylene glycol, pentaerythritol, and hexamethylenetetramine, in durable-press treatment of textile fabrics, in prevention of grain rot and mildew, as a corrosion inhibitor in oil wells, preservative and coagulant in latex rubber, and as a reducing agent (e.g., in precious metal recovery). It is also used in photograph developing processes and chrome printing (ACGIH, 1991; Budavari, 1996; Lewis, 1998).
c) Formaldehyde is present in building materials, insulations, and items such as glues, preservatives, permanent press fabrics, and other household products (NSC , 2002).

2) MEDICAL/VETERINARY

a) Therapeutically, formaldehyde has been used locally in pulpotomy and to treat massive hemorrhagic cystitis and hydatid cysts of the liver (Pain et al, 1988; Ranly & Horn, 1987; Vicente et al, 1990). It has also been used in veterinary medicine.
b) Formaldehyde has been used to sterilize dialysis machines. Dialysis patients using dialyzer machines sterilized with formaldehyde receive a small dose with each treatment (Hoy & Cestero, 1979; Sandler et al, 1979). Severe hypersensitivity reactions have been observed in a few of these dialysis patients, though the exact relationship of this to formaldehyde-sterilized equipment was unclear (Maurice et al, 1986). Currently other sterilizers are in use such as a mixture of hydrogen peroxide and peracetic acid.

3) ABUSE: Some individuals smoke tobacco or marijuana which has been soaked in formaldehyde and then dried in order to achieve "body numbness" and inebriation.

a) Formalin has been used to ensure the uniform distribution of phencyclidine (PCP) in adulterated marijuana cigarettes. Smoking the substance while still wet is believed to increase the length of time the drug can be smoked. This method has been described as "illy", "wet", "fry", "dip", "dank", "sherm" or "hydro" and described as marijuana soaked in "embalming fluid" (formalin) used to enhance the euphoric effects of marijuana (D'Onofrio et al, 2006; Nelson et al, 1999).

Overview

Life Support

Clinical Effects

0.2.1)

A) NOTE: This topic is limited to inhalation and/or dermal/ocular exposure of formaldehyde due to occupational/environmental exposure. Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.
B) SOURCES: Formaldehyde is a water-soluble and colorless gas at room temperature. Pure formaldehyde is not sold commercially because of its tendency to polymerize. It is most commonly available as formalin, a liquid that is created by mixing formaldehyde and water (usually 37 g of formaldehyde gas to 100 mL solution). Because this solution will polymerize, 10% to 15% of methanol (stabilized) is added. Other aqueous solutions of formaldehyde are referred to as unstabilized (methanol-free), and the solutions may contain n-butanol, ethanol, or urea. Formaldehyde is used in many manufacturing processes (particularly plastics and resins) and as a tissue fixative and embalming agent. It may also be used in the disinfection of hemodialysis machines. Formaldehyde is also used to manufacture urea-formaldehyde, which is found in building insulation and particle boards. It can often be measured at low levels indoors.
C) TOXICOLOGY: Formaldehyde is metabolized to formic acid by aldehyde dehydrogenase with eventual conversion to carbon dioxide and water via a folate-dependent pathway. Formaldehyde exposure can occur in various ways, and only mild symptoms are expected in very low concentrations. Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.
D) EPIDEMIOLOGY: Uncommon poisoning that can result in significant morbidity.
E) WITH POISONING/EXPOSURE

1) TOXICITY: Formaldehyde may be irritating to the eyes, skin, and mucous membranes. Health effects from environmental or occupational exposure can come from the off-gassing of formaldehyde from building materials. The effects may include headache; nausea; burning of the eyes, nose, and throat; skin rashes; coughing; and chest tightness. Sensitive individuals may have reactions at concentrations as low as 0.1 parts per million (ppm).
2) INHALATION: Respiratory tract irritation, rhinitis, anosmia, cough, dyspnea, wheezing, tracheitis, bronchitis, laryngospasm, pulmonary edema, headache, weakness, dizziness, and palpitations may result from inhalation.
3) DERMAL: Dermatitis, brownish discoloration of the skin, urticaria, and pustulovesicular eruptions may develop from dermal exposure.
4) OCULAR: Irritation, lacrimation, and conjunctivitis may develop with exposure to vapors. Eye exposure to solutions with high formaldehyde concentrations may produce severe corneal opacification and loss of vision. Solutions containing low formaldehyde concentrations may produce transient discomfort and irritation.
5) CHRONIC: Chronic exposures may increase the risk of cancer and occupational asthma.

0.2.20)

A) Formaldehyde has not been shown definitely to be teratogenic in animals. Formaldehyde probably presents little or no risk as a potential human teratogen.
B) Menstrual disorders have been reported in women occupationally exposed to formaldehyde, but these results are controversial. In experimental animal studies, some effects on spermatogenesis have been reported.
C) Occupational exposure at recommended limits is not thought to present a reproductive risk. Formaldehyde exposure among female hospital workers did not correlate with an increase in spontaneous abortion in one study, but did correlate in another.

1) Low-birthweight children have been reported in female workers exposed to urea-formaldehyde resin, but studies are inconclusive. Formaldehyde appears to cross the placental barrier in mice.

0.2.21)

A) Human data include nine studies that show statistically significant associations between site-specific respiratory neoplasms and exposure to formaldehyde or formaldehyde-containing products (HSDB , 2002). Occupational exposure to formaldehyde has been linked to the development of buccal and nasopharyngeal metaplasia/neoplasia, and to a lesser extent cancers of the nasal cavities.
B) Formaldehyde's role in lower respiratory tract cancer etiology has not been substantiated. Consensus on data collection and analysis methods will be necessary to evaluate the link between formaldehyde and lung cancer.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) This topic is limited to inhalation and/or dermal/ocular exposure of formaldehyde due to occupational/environmental exposure. Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.
B) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is symptomatic and supportive. Removal from inhalational exposure is the primary treatment. Supportive care with oxygen or bronchodilators can be administered.

C) MANAGEMENT OF SEVERE TOXICITY

1) Treatment for severe inhalational exposures is primarily supportive. Supplemental oxygen should be administered as needed. Mechanical ventilation may be needed. Bronchodilators can be administered. Patients with evidence of upper airway edema should be intubated early.

D) DECONTAMINATION

1) Remove from exposure and remove contaminated clothing. Wash exposed skin with soap and water. Irrigate exposed eyes with water.

E) AIRWAY MANAGEMENT

1) Patients who are comatose, have altered mental status, or have direct pulmonary or upper airway injury may need mechanical respiratory support and orotracheal intubation.

F) ANTIDOTE

1) None.

G) ENHANCED ELIMINATION

1) Hemodialysis will efficiently remove formaldehyde and formic acid, but systemic absorption of pure formaldehyde is rare as it forms a polymer. Hemodialysis should be used in cases of severe or worsening acidosis. Folate can also be administered to augment elimination of formic acid at a dose of 50 mg IV every 4 hours (CHILDREN: 1 mg/kg).

H) PATIENT DISPOSITION

1) HOME CRITERIA: Patients with mild eye, skin, or respiratory irritation can be managed at home with decontamination.
2) OBSERVATION CRITERIA: Patients with significant eye irritation, or more than mild pulmonary or skin irritation should be sent to a healthcare facility for evaluation and observation.
3) ADMISSION CRITERIA: Patients with evidence of pulmonary injury should be admitted to a monitored setting.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for hemodialysis.

I) PITFALLS

1) Inadequate dermal decontamination may worsen toxicity. Patients with inhalational/environmental exposure to formaldehyde may also be exposed to other chemicals. Patients with any evidence of upper airway involvement require early airway management before airway edema progresses.

J) PHARMACOKINETICS/TOXICOKINETICS

1) Formaldehyde is rapidly absorbed in the oral and inhalational routes and rapidly metabolized (half life, 1.5 minutes) to formic acid. Dermal absorption is minimal.

K) DIFFERENTIAL DIAGNOSIS

1) The differential diagnosis includes conditions that present as respiratory irritants from an inhalation exposure such as ammonia or chlorine.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

0.4.4)

A) PREHOSPITAL CARE: Irrigation with sterile water or saline, a commercial eye irrigation kit, or tap water should be started prior to admission.
B) CAUSTIC EYE DECONTAMINATION: Immediately irrigate each affected eye with copious amounts of water or sterile 0.9% saline for about 30 minutes. Irrigating volumes up to 20 L or more have been used to neutralize the pH. After this initial period of irrigation, the corneal pH may be checked with litmus paper and a brief external eye exam performed. Continue direct copious irrigation with sterile 0.9% saline until the conjunctival fornices are free of particulate matter and returned to pH neutrality (pH 7.4). Once irrigation is complete, a full eye exam should be performed with careful attention to the possibility of perforation.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Heent

3.4.3)

A) IRRITATION: Formaldehyde vapors produce irritation of the eyes, nose, and throat, most notably when the concentration exceeds 1 to 3 parts per million (ppm) (Horvath et al, 1988; Weber et al, 1988; Loomis, 1979).

1) As the concentration increases, the degree of irritation increases. Although uncommon, ocular irritation has been noted at levels as low as 0.05 ppm (Grant & Schuman, 1993; Bernstein et al, 1984).
2) In a study of 57 embalmers exposed to less than 2 ppm, 81% had irritant effects on the eyes (HSDB, 2006).
3) Human eye contact with a 40% solution of formaldehyde may cause immediate pain and epithelial clouding within minutes of exposure (Grant & Schuman, 1993).

a) The eye may appear normal or minimally affected for several hours. Delayed severe corneal injury and loss of vision may develop over 12 or more hours.

4) ANIMAL STUDIES: In the rabbit, formaldehyde was found to be a severe eye irritant (RTECS, 2006). Mechanism of ocular damage includes a breakdown of the blood-aqueous barrier, an increase in intraocular pressure, and an increase in cAMP in the aqueous humor (Krootila, 1988; Uusitalo, 1984).

B) VISION: Direct exposure can cause burns (Sittig, 1991), severe corneal opacification, and loss of vision (EPA, 1985); degree of injury is dose dependent (HSDB, 2006).

1) Eye exposure to solutions may result in transient or irreversible visual impairment, depending on the concentration of formaldehyde in the solution (Grant & Schuman, 1993).
2) Inhalation or ingestion of formaldehyde has NOT been found to affect vision in humans or animals (Grant & Schuman, 1993; Browning, 1965; Smyth et al, 1951).
3) Parenteral administration of formaldehyde to rabbits and rats did not induce blindness or alter the glucose uptake of the retina (Grant, 1962; Kornblueth & Ben-Shlomo, 1956).
4) Chronic oral administration of formaldehyde to mice caused structural changes in the retinal pigment epithelium (Kawano, 1975).
5) Injury to the retina or optic nerve has not been demonstrated in experimental animals administered formaldehyde intravenously (Grant & Schuman, 1993).

C) EYELID INJURY: Unintentional injection of the eyelids with formaldehyde in preparation for cosmetic surgery resulted in severe eyelid edema and tissue necrosis. Repeated surgical corrections were required for the resultant cicatricial entropions, ptosis, and scarring of the lateral and medial canthi and eyelids (Putterman, 1990).

3.4.5)

A) MORPHOLOGICAL CHANGES: Studies have found evidence of irritant effects and histopathological changes in the nasal mucosa of men with occupational exposure to formaldehyde, formaldehyde and wood dust, or formaldehyde and phenol (Edling et al, 1988; Holmstrom & Wilhelmsson, 1988; Berke, 1987).

3.4.6)

A) IRRITATION of the upper airway increases as the ambient air concentration of formaldehyde increases. Susceptible individuals may experience irritation with levels as low as 0.05 ppm (Light, 1985).

1) CASE SERIES: In a study of 57 embalmers exposed to less than 2 ppm, 75% developed irritant effects of the throat (HSDB, 2006).

Respiratory

3.6.2)

A) INJURY OF UPPER RESPIRATORY TRACT

1) WITH POISONING/EXPOSURE

a) Irritation continues at 2 to 3 ppm, and at 4 to 5 ppm there is more intense discomfort. An airborne concentration of 10 ppm can only be briefly tolerated; 10 to 20 ppm causes severe difficulty in breathing, cough, and intense irritation. Concentrations above 50 ppm can cause pulmonary edema, pneumonia, and bronchial irritation, which may result in death (OSHA, 2002a).
b) In a controlled study of 93 workers exposed to formaldehyde, cough, phlegm production, and chest congestion were the effects most closely associated with formaldehyde inhalation exposure (Malaka & Kodama, 1990).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Acute respiratory distress syndrome was reported in a worker exposed dermally to large amounts of resin phenol formaldehyde (Cohen et al, 1989).

C) BRONCHOSPASM

1) WITH POISONING/EXPOSURE

a) ASTHMA: Formaldehyde can produce reversible bronchoconstrictive, asthma-like effects under certain circumstances. Formaldehyde-induced asthma appears to occur infrequently (Nordman et al, 1985), but a brief exposure to as little as 3 ppm may provoke late asthma-like reactions in sensitized individuals (HSDB, 2006). All reported cases involved occupational exposure (Roto & Sala, 1996; Burge et al, 1985; Nordman et al, 1985; Hendrick et al, 1982; Anon, 1977; Hendrick & Lane, 1977).
b) A positive response to a laryngeal provocation test with formaldehyde has been reported (Roto & Sala, 1996), and formaldehyde-specific immunoglobulins have been measured in symptomatic or asymptomatic persons with formaldehyde exposure (Smedley, 1996).
c) A true immunologic basis for the development of formaldehyde-induced asthma has been questioned, as data from various studies conflict and formaldehyde-specific immunoglobulin development has not consistently correlated positively with respiratory symptoms (Smedley, 1996; Wantke et al, 1996; Grammer et al, 1990; Patterson et al, 1987; Frigas et al, 1984; Newhouse, 1982; Frigas et al, 1981).

D) ASTHMA

1) WITH POISONING/EXPOSURE

a) Bronchial asthma, including episodes of wheezing and persistent cough, has been reported in hospital workers exposed to formalin vapor (Hendrick et al, 1982; Hendrick & Lane, 1977; Hendrick & Lane, 1975; Sakula, 1975). In some patients the symptoms appeared several hours after exposure (Hendrick & Lane, 1977).

E) DISORDER OF RESPIRATORY SYSTEM

1) ADULT studies include the following:

a) CASE SERIES: Among 15 nonsmoking adults with bronchial hyperresponsiveness to histamine who were exposed to up to 0.85 mg/m(3) formaldehyde vapor for 90 minutes, no significant changes in forced expiratory volume in 1 second (FEV1), airway resistance (Raw), or flow-volume curve could be detected during or after exposure. In this study, histamine challenge tests performed immediately after exposure showed no evidence of change in bronchial reactivity. No late reactions were registered during the first 16 hours (Harving et al, 1990).
b) CASE SERIES: In tests on healthy adults exposed to 2 ppm formaldehyde, there was no change in FVC and there were positive changes in FEV(1) and MEF(50%) with moderate exercise following up to 40 minutes of exposure. Although the subjects reported upper respiratory irritation, no lower respiratory tract impairment or bronchoconstriction occurred (Schachter et al, 1986).

2) PEDIATRIC studies include the following:

a) CASE SERIES: There was a significant correlation between formaldehyde levels in the homes of 268 children and chronic adverse respiratory effects including asthma and chronic bronchitis. Lower respiratory signs in adult subjects did not correlate with airborne formaldehyde levels (Krzyzanowski et al, 1990).

3.6.3)

A) ANIMAL STUDIES

1) INTERSTITIAL PNEUMONIA

a) Rats, dogs, monkeys, and guinea pigs were exposed by inhalation to formaldehyde at 4.6 mg/m(3) for 8 hours per day, 5 days per week, for 6 weeks. Histopathologic examination of the animals' lungs revealed interstitial inflammation. The authors were unable definitively to attribute these changes to formaldehyde inhalation (Coon et al, 1970).

Neurologic

3.7.2)

A) NEUROPATHY

1) CNS: The rapid metabolism and high reactivity of formaldehyde decrease the likelihood that brain formaldehyde concentrations would become high except under extraordinary conditions (Anon, 1984).

Gastrointestinal

3.8.2)

A) NAUSEA

1) WITH POISONING/EXPOSURE

a) Nausea has been reported following occupational or environmental exposure to formaldehyde vapors (Goldfrank et al, 1994).

B) INJURY OF GASTROINTESTINAL TRACT

1) WITH POISONING/EXPOSURE

a) Acute ingestion of formalin solution can result in significant gastrointestinal injury. Please refer to the FORMALIN management for further information.

Hepatic

3.9.2)

A) LIVER DAMAGE

1) WITH POISONING/EXPOSURE

a) Hepatotoxicity has been reported following the inhalation of formaldehyde gas, although hepatitis serologies were not performed (Beall & Ulsamer, 1984).

Genitourinary

3.10.2)

A) TOXIC NEPHROPATHY

1) WITH POISONING/EXPOSURE

a) CASE REPORT: One study reported 4 cases of nephrotic syndrome after exposure to toxic concentrations of formaldehyde in newly built homes. Membranous nephropathy was confirmed by biopsy; the authors found that the 4 patients shared a particular HLA type on the major histocompatibility complex and speculated that the patients were genetically susceptible to "triggering" of immune reactions by formaldehyde exposure. This has not been confirmed by other studies (Breysse et al, 1994).

Hematologic

3.13.2)

A) HEMOLYTIC ANEMIA

1) WITH POISONING/EXPOSURE

a) SERUM SICKNESS/AUTOIMMUNE HEMOLYTIC ANEMIA: Dialysis patients, who receive a small dose of formaldehyde with each treatment, may develop circulating immune complexes resulting in a serum sickness-like syndrome. The most frequent sequela is a type of autoimmune hemolytic anemia; rarely, peripheral eosinophilia may occur (Fassbinder et al, 1979; Hoy & Cestero, 1979; Sandler et al, 1979). The relation to formaldehyde remains uncertain.

Dermatologic

3.14.2)

A) CONTACT DERMATITIS

1) WITH POISONING/EXPOSURE

a) Allergic dermatitis has developed as a result of skin exposure, as well as exposure to formaldehyde vapors. Findings include simple drying, erythema, urticaria, eczematous lesions, desquamation, hyperesthesias, and angioneurotic edema (Andersen & Maibach, 1984; Simon et al, 1984; Lembo et al, 1982; Lindskov, 1982; Pedersen, 1980; Loomis, 1979; Moran & Martin-Pascual, 1978).
b) The ability of the nonliquid, nonvolatile proallergen of formaldehyde, N-hydroxy methyl succinimide, has been investigated by in vitro penetration studies in human epidermis.

1) Compared with the standard test, 1% formaldehyde in water, N-hydroxy methyl succinimide equal to 0 to 8 mg formaldehyde gave a similar penetration profile. Results were also confirmed by a guinea pig maximization test on animals sensitized to formaldehyde (Hansen et al, 1989).

c) A single large exposure may result in sensitization and subsequent contact dermatitis (Kanerva et al, 1994).

B) DERMATITIS

1) WITH POISONING/EXPOSURE

a) OCCUPATIONAL dermatitis may occur after use of urea-formaldehyde resin (Vale & Ryckroft, 1988) and para-tertiary-butylphenol formaldehyde resin (Fisher, 1987).
b) Dermal exposure may result in irritant dermatitis (Budavari, 1996).
c) Hardening and roughness due to superficial coagulation of the keratin layer may occur after contact with aqueous solutions (Morgan, 1989).

Immunologic

3.19.2)

A) BRONCHOSPASM

1) WITH POISONING/EXPOSURE

a) Formaldehyde can produce reversible bronchoconstrictive, asthma-like effects under certain circumstances. Formaldehyde-induced asthma is an infrequent phenomenon (Nordman et al, 1985), but a brief exposure to as little as 3 ppm may provoke late asthma-like reactions in sensitized individuals (HSDB, 2006).

1) All reported cases involved occupational exposure (Roto & Sala, 1996; Burge et al, 1985; Nordman et al, 1985; Cockcroft et al, 1982; Hendrick et al, 1982; Anon, 1977; Hendrick & Lane, 1977).

b) A true immunologic basis for the development of formaldehyde-induced asthma has been questioned, as data from various studies conflict and formaldehyde-specific immunoglobulin development has not consistently correlated positively with respiratory symptoms (Smedley, 1996; Wantke et al, 1996; Grammer et al, 1990; Patterson et al, 1987; Frigas et al, 1984; Newhouse, 1982; Frigas et al, 1981).
c) Formaldehyde exposure in humans rarely induces specific IgE, IgG, or IgM to formaldehyde (Smedley, 1996). Immunologic reactions from formaldehyde exposure may be delayed by hours to months (Breysse et al, 1994; Porter, 1975).
d) Long-term exposure to formaldehyde or urea-formaldehyde foam insulation did not result in an effect on immune function in tested asthmatics (Pross et al, 1987).
e) A positive response to a laryngeal provocation test with formaldehyde was reported in a worker with a history of occupational laryngitis. Nonspecific provocation tests were not performed (Roto & Sala, 1996).

B) ACUTE ALLERGIC REACTION

1) CASE REPORT: Three cases of allergy to dental compounds containing formaldehyde have been reported. Effects appeared within 1 to 10 hours and included generalized urticaria, angioedema, bronchoconstriction, cardiovascular abnormalities, and loss of consciousness (Ebner & Kraft, 1991).

a) Patch, rub, and prick tests to formaldehyde and other suspected chemicals were negative; diagnosis was based on finding elevated serum IgE levels and specific IgE to formaldehyde human serum albumin complexes in all patients' sera.

2) A report described 6 dialysis patients who presented with anaphylactic shock and formaldehyde-human serum albumin IgE antibody complexes. Most of these patients' signs subsided with cessation of exposure (Bousquet & Michel, 1991).

C) NEPHROTIC SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Nephrotic syndrome was reported in 4 people after they were exposed to toxic concentrations of formaldehyde in newly built homes. Membranous nephropathy was confirmed by biopsy; the authors found that the 4 patients shared a particular haplotype on the major histocompatibility complex and speculated that the patients were genetically susceptible to "triggering" of immune reactions by formaldehyde exposure (Breysse et al, 1994).

D) DISORDER OF IMMUNE FUNCTION

1) WITH POISONING/EXPOSURE

a) BUILDING-RELATED COMPLAINTS: Immunologic monitoring may be useful in investigating allergic-type complaints (Thrasher et al, 1989; Thrasher et al, 1988). Further investigation has not supported this concept (Kramp et al, 1989; Greenberg & Stave, 1989; Thrasher et al, 1989).

1) A case of building-related health complaints with symptoms involving the eyes, nose, sinuses, throat, lungs, musculoskeletal system, and CNS has been reported (Thrasher et al, 1989).

a) The relationship among frequency of symptoms; antibodies to albumin conjugates of formaldehyde (HCHO), toluene diiso cyanates (TDI) and trimellitic anhydride (TMA) and volatile organic chemicals was studied.
b) The indoor air concentration of these substances did not exceed Fed-OSHA and American Conference of Governmental Industrial Hygienists (ACGIH) permissible standards.
c) Anti-HCHO, -TDI, and -TMA isotypes were found in 12 of 14 full-time employees and were not detectable in one part-time employee. Symptoms and the geometric mean titers to conjugates were not correlated.

E) CONTACT DERMATITIS

1) WITH POISONING/EXPOSURE

a) Formaldehyde is a dermal allergen and respiratory irritant (Morgan, 1989). Allergic reactions, including eczematoid dermatitis after repeated contact with the solution, are possible. Clothing treated with formaldehyde has also caused dermatitis (HSDB, 2006).
b) Long-term exposure to urea-formaldehyde foam insulation has not been shown to affect immunologic function; short-term exposure resulted in minor immunologic changes (Pross et al, 1987).

F) TRANSFUSION REACTION DUE TO SERUM PROTEIN REACTION

1) Dialysis patients, who receive a small dose of formaldehyde with each treatment, may develop circulating immune complexes resulting in a serum sickness-like syndrome. The most frequent sequela is a type of autoimmune hemolytic anemia; rarely, peripheral eosinophilia may occur (Fassbinder et al, 1979; Hoy & Cestero, 1979; Sandler et al, 1979).

G) IMMUNE SYSTEM FINDING

1) WITH POISONING/EXPOSURE

a) A cross-sectional study was conducted to evaluate the levels of circulating immune/inflammation markers in formaldehyde-exposed workers compared to workers not exposed to formaldehyde. A total of 94 workers (43 exposed to a median formaldehyde level of 1.28 ppm (levels ranging from 0.32 to 5.61) and 51 unexposed to formaldehyde (median level of 0.026 ppm with levels ranging from 0.015 to 0.026) were evaluated, comparing 38 markers. Of the 38 immune/inflammation markers, the median levels of 10 were significantly different between the exposed and the unexposed workers. Eight of the 10 markers were significantly lower in the formaldehyde-exposed worker compared to the unexposed worker and 2 of the 10 markers were significantly higher in the exposed worker compared to the unexposed worker. After adjusting for various confounding factors and adhering to a false discovery rate cutoff of 10%, 2 markers (CXCL11 and TARC) remained significantly lower in the formaldehyde exposed worker compared to the unexposed worker, suggesting the development of immunosuppression in workers occupationally exposed to formaldehyde (Seow et al, 2015).

3.19.3)

A) ANIMAL STUDIES

1) LACK OF EFFECT

a) Long-term exposure to formaldehyde or urea-formaldehyde foam insulation did not result in an effect on immune function in tested asthmatic patients (Pross et al, 1987).

Reproductive

3.20.1)

1) Low-birthweight children have been reported in female workers exposed to urea-formaldehyde resin, but studies are inconclusive. Formaldehyde appears to cross the placental barrier in mice.

3.20.2)

A) LACK OF EFFECT

1) Formaldehyde probably presents little or no risk as a potential human teratogen.

B) ANIMAL STUDIES

1) LACK OF EFFECT

a) Formaldehyde has not been shown definitely to be teratogenic in animals.
b) Formaldehyde was found NOT to be teratogenic in the mouse, rat, guinea pig, or dog (Schardein, 1993).
c) Formaldehyde has been uniformly inactive for causing birth defects in several studies in experimental animals, including mice exposed by the oral route (Marks, 1980), rats exposed by inhalation (Gofmekler & Bonashevskaya, 1969; Sheveleva, 1971), dogs with dietary exposure (Hurni & Ohder, 1973), and in hamsters exposed by skin painting (Overman, 1985). In some of these studies, formaldehyde was feto- or embryotoxic.

2) SKELETAL MALFORMATION

a) Toxic effects on the embryo or fetus including fetotoxicity and fetal death have been observed in mouse studies. Craniofacial, musculoskeletal and other specific developmental abnormalities have also been observed (RTECS, 1999).

3) CHROMOSOME DISORDER

a) In rat studies, cytologic changes including changes in somatic cell genetic material have been observed in the embryo or fetus. Toxic effects on the newborn include changes in growth statistics and biochemical, metabolic and behavioral effects (RTECS, 1999).

3.20.3)

A) SPONTANEOUS ABORTION

1) Menstrual disorders and increased spontaneous abortions have been seen with formaldehyde (EPA, 1985) Schardein, 1985).
2) An epidemiological study demonstrated a significantly increased risk of prolonged time to pregnancy (TTP) and spontaneous abortion among the wives of 302 male workers occupational exposed to formaldehyde compared with the partners of 305 male controls (healthy volunteers). After adjusting for confounding factors (eg, body mass index, alcohol exposure, cigarette intake), a significantly increased risk for prolonged TTP (odds ratio [OR], 2.828; 95% CI, 1.081 to 7.406) and spontaneous abortion (OR, 1.916; 95% CI, 1.103 to 3.329) exists with exposure to formaldehyde. Dose-dependent increased risks in prolonged TTP and spontaneous abortion were found by comparing a high-exposure group (n=151) with a low-exposure group (n=151); however, the increases were not statistically significant (Wang et al, 2012).
3) CASE SERIES - Exposure to formaldehyde-based disinfectants was one of the risk factors for spontaneous abortions in a group of 96 cosmetologists (John et al, 1994).
4) Another study found a 3.5-fold increased risk for spontaneous abortions in female laboratory workers exposed to formalin, but no increases in birth defects were seen (Taskinen et al, 1994).

B) BIRTH WEIGHT SUBNORMAL

1) Oligodysmenorrhea and low-birthweight children have been reported from female workers exposed to urea-formaldehyde resin, but studies are inconclusive (Shumilina, 1975). Occupational exposure at recommended limits is not thought to present a reproductive risk (AMA, 1985).

C) ANIMAL STUDIES

1) PREGNANCY DISORDER

a) Post-implantation mortality has been reported as a toxic effect on fertility in mouse studies (RTECS, 1999).

2) Formaldehyde appears to cross the placental barrier in mice. Levels comparable to those found in pregnant mice were seen in the fetuses; fetal mice eliminated formaldehyde more slowly than the mothers (Katakura et al, 1993).

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS50-00-0 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

3.21.3)

A) CARCINOMA

1) Formaldehyde reacts with HYDROGEN CHLORIDE to form BIS-CHLOROMETHYL ETHER, a known human carcinogen (EOSH, 1982).
2) A number of comprehensive studies have critically evaluated the carcinogenicity of formaldehyde among industrial workers and humans in general (Coggon et al, 2003; Hauptmann et al, 2003; Squire & Cameron, 1984; Blair et al, 1986) Pattanen et al, 1985; (Kauppinen & Niemela, 1985; Infante & Schneiderman, 1986) Tambuzzo & Waddel, 1987; (Collins et al, 1988).
3) One case-control epidemiologic study suggests an association of nasopharyngeal cancer in older men with probable exposure to formaldehyde at high levels 20 or more years prior to death (Roush et al, 1987).
4) In order to assess the possible human carcinogenicity of formaldehyde, a retrospective cohort mortality study of workers exposed for at least three months to formaldehyde in three garment facilities which produced permanent press garments, was undertaken by Stayner et al (1988).

a) The average (TWA) formaldehyde exposure at the three plants monitored in 1981 and 1986 by NIOSH was 0.15 ppm but past exposures may have been substantially higher. A total of 11,030 workers contributing 188,025 person-year were included in the study.
b) A statistically significant excess in mortality from cancer of the buccal cavity (SMR=343) and connective tissue (SMR=364) was observed.
c) Mortality from cancers of the buccal cavity, leukemias and other lymphopoietic neoplasms increased with duration of formaldehyde exposure and were also found to be the highest among workers first exposed during a time period of high potential formaldehyde exposures in this industry (1955-1962).
d) It should be recognized that these findings are based on relatively small numbers and that compounding by other factors may still exist.
e) The results from this investigation, although far from conclusive, do provide evidence of a possible relationship between formaldehyde exposure and the development of upper respiratory cancers (buccal), leukemias, and other lymphopoietic neoplasms in humans.

5) Two retrospective European studies which examined all cases of cancers of the nasal cavity, paranasal sinuses, and nasopharynx in Denmark (Olsen & Asnaes, 1986) and the Netherlands (Hayes, 1986) both concluded that there was an approximate two-fold excess risk of these cancers in persons who had ever been exposed to formaldehyde.
6) OCCUPATIONAL EXPOSURE - Occupational exposure to formaldehyde was NOT associated with cancers of the sinuses or nasal cavities in one study. Persons exposed to both formaldehyde and wood dust (known to be associated with nasal adenocarcinoma) had a higher risk of developing this form of cancer than those exposed only to wood dust (Luce et al, 1993).
7) In addition to the occupational studies, a study in Washington state concluded that persons living in mobile homes are at increased risk for nasopharyngeal cancer, but not oro- or hypopharyngeal cancers or sinus or nasal cavity cancers (Vaughan, 1986). In this study, the risk was increased up to 5.5 times for ten or more years of residence in mobile homes. No excess cancer risk was seen with exposure to urea-formaldehyde foam insulation or new pressed wood, however.
8) A mortality cohort study with extensive follow-up, involving 25,000 industrial workers in the United States who were employed at 1 of 10 industrial plants before 1966 and followed through 1994, was conducted to analyze formaldehyde occupational exposure and mortality from lymphohematopoietic malignancies. There were 161 deaths from lymphohematopoietic malignancies in formaldehyde-exposed workers as compared with 17 deaths among un-exposed workers. For workers exposed to formaldehyde levels at 2 to 3.9 ppm and at 4 ppm or more, the relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43), respectively, as compared with 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03) for workers exposed to formaldehyde levels at 0.5 to 0.9 ppm and at 1 ppm or more, respectively, although the relative risk for leukemia was associated with peak formaldehyde exposure, average exposure intensity, and duration of exposure, and not with cumulative exposure (Hauptmann et al, 2003). Potential limitations of this study included occupational exposures to other chemicals, possible misclassification of average and cumulative exposure and of duration of exposure, and lack of information on exposures during the follow-up period (1980 to 1994) resulting in an underestimation of exposure for individuals working after 1980.
9) A large study of industrial workers exposed to formaldehyde in 10 US formaldehyde-producing or using facilities was conducted to analyze formaldehyde occupational exposure and the risk of solid cancers. Relative risks for nasopharyngeal cancer increased with average exposure intensity, highest peak exposure, cumulative exposure, and duration of exposure. Relative risks for prostate cancer were elevated for some measures of exposure, however the trend was inconsistent. Exposure did not appear to be associated with brain, pancreas, or lung cancers (Hauptmann et al, 2004).
10) A reanalysis of the National Cancer Institute's cohort study data of the relationship between formaldehyde exposure and mortality from nasopharyngeal cancer provided little evidence to support their suggestion of a causal association between formaldehyde exposure and mortality from nasopharyngeal cancer (Marsh & Youk, 2005).

B) PULMONARY CARCINOMA

1) The National Cancer Institute study of formaldehyde-exposed employees has been re-analyzed by several investigators. Sterling & Weinkam (1994) found no increased mortality from respiratory cancers overall, but there was a trend of increasing mortality with increasing cumulative exposure. Blair et al (1986) showed a nonsignificant but slightly elevated risk of lung cancer mortality for every exposure category, but no dose response.
2) In an independent and updated mortality study on the same plant featured in the previous National Cancer Institute study, there was "little evidence" of increased rates of lung cancer in long-term workers in relation to formaldehyde exposure. Short-term employees did have significantly increased death rates from several causes, including lung cancer (Marsh et al, 1996)

a) It is difficult to draw firm conclusions from the NCI study because only seven cases of oral cancer were involved, and because it used the method of comparing death rates with standardized population figures rather than a matched control group.

3) Most epidemiologic studies have found a similar result, of a slightly elevated risk for lung cancer mortality with formaldehyde exposure (Coggon et al, 2003; Callas et al, 1996; Sterling & Weinkam, 1996).

C) SKIN CARCINOMA

1) MELANOMA - Holmstrom & Lund (1991) present 3 cases of malignant mucosal melanoma of the nasal cavity in patients who have been occupationally exposed to formaldehyde.

a) None of these patients had family histories of melanomas. No other risk factors were apparent. All patients had history for occupational formaldehyde exposure for more than 10 years.

D) LEUKEMIA AND LYMPHOMA

1) A systematic review of the literature, namely occupational cohort and population-based case-control studies, found no significantly increased risk for all leukemias and myeloid leukemia in people who were exposed to formaldehyde. However, in isolated exceptions, peak exposure was associated with significantly increased risk of myeloid leukemia, with a relative risk (RR) of 2.79 (95% CI, 1.08 to 7.21) for those in the highest exposure category. In addition, peak exposure was also associated with significantly increased risk of Hodgkin lymphoma, with a RR of 3.96 (95% CI, 1.31 to 12.02) for the highest exposure category (4 ppm or greater) only, based on 11 deaths (Checkoway et al, 2012).

E) LYMPHOMA-LIKE DISORDER

1) Exposure to formaldehyde in the Finnish woodworking industry was associated with a nonsignificant 2.5-fold elevated risk for developing lymphoma or leukemia (Partanen et al, 1993).

F) BREAST CARCINOMA

1) OCCUPATIONAL EXPOSURE - Suggestive association between occupational exposure to formaldehyde and deaths from breast cancer was seen in a case-control study using mortality records from 24 states from 1984 to 1989 (Cantor et al, 1995).

G) LACK OF EFFECT

1) LEUKEMIA AND LYMPHOMA

a) A systematic review of the literature, namely occupational cohort and population-based case-control studies, found no significantly increased risk for all leukemias and myeloid leukemia in people who were exposed to formaldehyde. However, in isolated exceptions. peak exposure was associated with significantly increased risk of myeloid leukemia, with a relative risk (RR) of 2.79 (95% CI, 1.08 to 7.21) for those in the highest exposure category. In addition, peak exposure was also associated with significantly increased risk of Hodgkin lymphoma, with a RR of 3.96 (95% CI, 1.31 to 12.02) for the highest exposure category (4 ppm or greater) only, based on 11 deaths (Checkoway et al, 2012).

3.21.4)

A) CARCINOMA

1) By RTECS criteria, formaldehyde was found to be both an equivocal tumorigenic and a carcinogenic agent in the rat with sense organs and special senses tumors. It has been classified as an equivocal tumorigenic agent by RTECS criteria with tumors at the site of application, of the skin and appendages and of the sense organs/special senses. In the mouse, formaldehyde is classified as an equivocal tumorigenic agent by RTECS criteria with tumors at the site of application (RTECS, 1999).
2) The mechanism of formaldehyde-induced nasal cancer in experimental animals involves DNA-protein crosslinks (Conaway et al, 1996).
3) An increased incidence of nasal squamous cell carcinomas was observed in long-term inhalation studies in rats and in mice. The classification of B1 is further supported by in vitro genotoxicity data and formaldehyde's structural relationships to other carcinogenic aldehydes such as acetaldehyde (HSDB , 2002).
4) SQUAMOUS CELL CARCINOMA of the nasal cavity in rats and precancerous nasal lesions in mice due to prolonged high dose formaldehyde exposure have been demonstrated (Sellakumar et al, 1980; Albert et al, 1982; Swenberg et al, 1980; Squire & Cameron, 1984). Although nasal carcinomas are reproducible in rat models the comparative anatomy between humans and rodents must be considered. Rats and mice are obligate nasal breathers whereas humans are partial mouth breathers (Squire & Cameron, 1984). Therefore, the rodents have proportionately greater nasal exposure to formaldehyde which they inspire during inhalation studies.

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor vital signs, mental status, comprehensive metabolic panel, CBC, and arterial or venous blood gas in patients who develop more that irritation symptoms.
B) Formic acid concentrations can be obtained but will probably not be obtainable in a clinically useful time frame.
C) Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.
D) Monitor pulse oximetry and obtain a chest radiograph in patients with persistent respiratory symptoms.

4.1.2)

A) FORMALDEHYDE PLASMA LEVELS are not widely available.

4.1.4)

A) OTHER

1) OTHER

a) ALLERGIC REACTION: If immunologic reaction to formaldehyde exposure is suspected, serum antibodies to formaldehyde (formaldehyde-human serum albumin complexes are available, by ELISA) can be analyzed.

2) DERMAL

a) DERMATOLOGIC TESTING: Patch testing and prick testing are commonly used to test for dermatologic allergy. Skin testing with aqueous formaldehyde should be used with caution since anaphylactic reactions have been reported in a few patients.

3) INHALATION PROVOCATION TEST

a) Inhalation provocation tests have been used following occupational exposure to inhaled formalin (Hendrick & Lane, 1977).

4) MONITORING

a) The presence of a small amount of endogenously derived formate in human urine is normal; however, formate derived from the metabolism of formaldehyde, several other industrial compounds (methanol, halomethanes, acetone) and some pharmaceutical compounds (methenamine, N-methyltriazine, hexamethyl-melanine, N-isopropyl-methoxamine, ephedrine and methylephedrine) may elevate the urine formate concentration above the normally expected values.
b) Given the poor understanding of the normal variation of formate concentration in the urine, its use as a biological indicator of chemical exposure is questionable. Without appreciable skin penetration, reliance upon air monitoring alone may be more practical.
c) Urinary formic acid levels were shown to be subject to 30-fold inter- and intra-individual variation and did not correlate with known exposures to formaldehyde. Formic acid is not a suitable biomarker for formaldehyde exposure (Schmid et al, 1994).

Methods

1) AIR: A sampling method for monitoring personal exposure to formaldehyde is described (Gaertner, 1988). The method consists of drawing air through a solid solvent tube containing silica gel impregnated with 20% sodium bisulfite.

a) The formaldehyde collected reacts to form the sodium formaldehyde bisulfite addition product. This salt may then be desorbed with water and the resulting solution analyzed for formaldehyde using the chromatropic acid colorimetric method.
b) The storage stability of formaldehyde on 20% bisulfite/silica gel was excellent. Collected formaldehyde may be stored in these tubes for over one month.
c) The 20% bisulfite impregnated silica gel tubes can be recommended for personal monitoring in air, even at a sampling rate of 1 ppm over the humidity range tested (20 to 80% relative humidity). The capacity of the tubes should be more than adequate for industrial hygiene monitoring.

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with evidence of pulmonary injury should be admitted to a monitored setting.

6.3.1.2) HOME CRITERIA/ORAL

A) Patients with mild eye, skin, or respiratory irritation can be managed at home with decontamination.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a poison center or medical toxicologist for assistance in managing severe poisonings and for recommendations on determining the need for hemodialysis.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with significant eye irritation, or more than mild pulmonary or skin irritation should be sent to a healthcare facility for evaluation and observation.

Monitoring

Oral Exposure

6.5.1)

A) PREHOSPITAL: Remove from exposure and remove contaminated clothing. Wash exposed skin with soap and water. Irrigate exposed eyes with water.
B) Because formaldehyde spontaneously polymerizes in water, most commercial liquid formulations contain methanol to limit polymerization. This topic is limited to inhalation and/or dermal/ocular exposure of formaldehyde due to occupational/environmental exposure. Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.

6.5.2)

A) Because formaldehyde spontaneously polymerizes in water, most commercial liquid formulations contain methanol to limit polymerization. This topic is limited to inhalation and/or dermal/ocular exposure of formaldehyde due to occupational/environmental exposure. Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.

6.5.3)

A) MONITORING OF PATIENT

1) Monitor vital signs, mental status, comprehensive metabolic panel, CBC, and arterial or venous blood gas in patients with more than irritation symptoms.
2) Formic acid concentrations can be obtained but will probably not be obtainable in a clinically useful time frame.
3) Refer to the FORMALIN management following an ACUTE ingestion/instillation of formalin.

B) HYPOTENSIVE EPISODE

1) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

2) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

3) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) Begin irrigation immediately with copious amounts of water or sterile 0.9% saline, which ever is more rapidly available. Lactated Ringer's solution may also be effective. Once irrigation has begun, instill a drop of local anesthetic (eg, 0.5% proparacaine) for comfort; switching from water to slightly warmed sterile saline may also improve patient comfort (Singh et al, 2013; Spector & Fernandez, 2008; Ernst et al, 1998; Grant & Schuman, 1993a). In one study, isotonic saline, lactated Ringer's solution, normal saline with bicarbonate, and balanced saline plus (BSS Plus) were compared and no difference in normalization of pH were found; however, BSS Plus was better tolerated and more comfortable (Fish & Davidson, 2010).

1) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (check pH every 30 minutes), pH of 7.0 to 8.0, and remain so for 30 minutes after irrigation is discontinued (Spector & Fernandez, 2008; Brodovsky et al, 2000). After severe alkaline burns, the pH of the conjunctival sac may only return to a pH of 8 or 8.5 even after extensive irrigation (Grant & Schuman, 1993a). Irrigating volumes up to 20 L or more have been used to neutralize the pH (Singh et al, 2013; Fish & Davidson, 2010). Immediate and prolonged irrigation is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
2) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993a).
3) For significant alkaline or concentrated acid burns with evidence of eye injury irrigation should be continued for at least 2 to 3 hours, potentially as long as 24 to 48 hours if pH not normalized, in an attempt to normalize the pH of the anterior chamber (Smilkstein & Fraunfelder, 2002). Emergent ophthalmologic consultation is needed in these cases (Spector & Fernandez, 2008).

6.8.2)

A) BURN

1) After splash exposure to significant concentrations (25%) severe eye injury may develop in a delayed fashion (12 hours or more) despite a benign initial presentation (Grant & Schuman, 1993). Patients with exposure to significant concentrations of formaldehyde should be evaluated by an ophthalmologist. The following treatment information is derived from experience with other corrosives.
2) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000a).
3) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000a; Singh et al, 2013):

a) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
b) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
c) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
d) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.

4) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):

a) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
b) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
c) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
d) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
e) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
f) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.

5) SUMMARY

a) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.

6) ARTIFICIAL TEARS

a) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

7) TOPICAL CYCLOPLEGIC

a) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

8) TOPICAL ANTIBIOTICS

9) PAIN CONTROL

a) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993a). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

10) SUMMARY

a) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.

11) ARTIFICIAL TEARS

a) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

12) PAIN CONTROL

13) CARBONIC ANHYDRASE INHIBITOR

a) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).

14) TOPICAL STEROIDS

a) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993b).
b) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
c) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000).

1) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000).

15) ASCORBATE

a) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
b) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
c) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993b). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000).

16) CITRATE

a) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
b) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
c) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993b). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000).

17) COLLAGENASE INHIBITORS

a) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
b) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
c) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).

18) ANTIBIOTICS

a) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).

19) TOPICAL CYCLOPLEGIC

a) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

20) SOFT CONTACT LENSES

a) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.

21) SURGICAL THERAPY CAUSTIC EYE INJURY

a) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
b) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
c) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
d) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
e) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
f) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993a).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

1) Hemodialysis may be effective in removing formaldehyde and formic, but systemic absorption of pure formaldehyde is rare as it forms a polymer on contact with water. Hemodialysis should be considered in those patients with severe acid-base disturbances refractory to conventional therapy or in patients with acute renal failure (Jacobsen & McMartin, 1986; Koppel et al, 1990).

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) ACUTE EXPOSURE - Exposure to 700 ppm for 8 hours was fatal to cats; a 2 hour exposure was fatal to mice. Mice and rabbit fatalities occurred after 10 hours exposure to 15 to 16 ppm (ACGIH, 1991).
2) CHRONIC EXPOSURE - Rats exposed to air concentrations of 0.5 ppm for a few days showed inhibition of mucociliary action. Rats exposed to 1.6 ppm for 90 days showed a yellowing of the fur, but no other treatment related effects (i.e., alveolar macrophage number and activity, or lung weight changes). At a concentration of 4.6 ppm, a decrease in body weight was noted. 8 ppm caused a decrease in overall body weight, as well as decreased liver weight, signs of nasal irritation, and a decrease in phagocytic activity of alveolar macrophages (ACGIH, 1991).

Maximum Tolerated Exposure

1) The workplace ceiling limit (NIOSH) is 0.016 ppm (8 hour TWA) or 0.1 ppm for 15 minutes. The odor threshold is around 0.5 to 1 ppm and people may begin to experience symptoms of respiratory irritation around the odor threshold (National Institute for Occupational Safety and Health, 2009; Agency for Toxic Substances and Disease Registry, 2008).

1) Typical reactions to airborne concentrations, include (ACGIH, 1991; Casteel et al, 1987; Hathaway et al, 1996):

1) 0.1 to 0.3 ppm - lowest level where irritation is reported
2) 0.8 ppm - odor threshold
3) 1 to 2 ppm - irritation threshold, mild
4) 2 to 3 ppm - irritation of eyes, nose, and throat
5) 4 to 5 ppm - increasing irritation of mucous membranes and prominent lacrimation
6) 10 to 20 ppm - profuse tearing, severe burning sensation, cough; can be tolerated for only a few minutes
7) 50 to 100 ppm - will cause serious injury in 5 to 10 minutes

2) Airborne formaldehyde concentrations in a gross anatomy laboratory ranged from 0.07 to 2.94 ppm, far exceeding the ACGIH ceiling value of 0.3 ppm, and over 30% of the subjects were exposed to an 8-hr TWA exceeding the OSHA action level of 0.5 ppm. In this study, signs and symptoms included irritation of the eyes, nose, throat and airways, decreased FVC and FEV3, and increased FEV1/FVC (Akbar-Khanzadeh et al, 1994).
3) Dermal exposure to solutions of 2% to 10% may result in blisters, fissures, and urticaria (Casteel et al, 1987).
4) Contact of the human eye with aqueous solutions of formaldehyde has caused injuries ranging from severe irreversible corneal opacification and loss of vision, to minor transient injury or temporary discomfort, depending upon whether the solutions were of high or low concentrations (Grant & Schuman, 1993).
5) Solutions of 25% to 44% formaldehyde may cause severe corneal damage (Hathaway et al, 1996).
6) At levels of 1 to 10 ppm appreciable eye irritation may be seen on initial exposure. At levels of 25 to 50 ppm tissue damage is likely (Clayton & Clayton, 1981).

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Formaldehyde

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling: 0.3 ppm

b) Notations and Endnotes:

1) Carcinogenicity Category: A2
2) Codes: SEN
3) Definitions:

a) A2: Suspected Human Carcinogen: Human data are accepted as adequate in quality but are conflicting or insufficient to classify the agent as a confirmed human carcinogen; OR, the agent is carcinogenic in experimental animals at dose(s), by route(s) of exposure, at site(s), of histologic type(s), or by mechanism(s) considered relevant to worker exposure. The A2 is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans.
b) SEN: The designation SEN refers to the potential for an agent to produce sensitization, as confirmed by human or animal data. The notation does not imply that this is the critical effect or that this is the sole basis for the TLV. Although, for those TLVs that are based on sensitization, the TLV is meant to protect workers from induction of this effect, but cannot protect workers who have already become sensitized. The notation should be used to assist in identifying sensitization hazards and reducing respiratory, dermal, and conjunctival exposures to sensitizing agents in the workplace. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): URT and eye irr
d) Molecular Weight: 30.03

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS50-00-0 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Formaldehyde
2) REL:

a) TWA: 0.016 ppm
b) STEL:
c) Ceiling: 0.1 ppm [15-minute]
d) Carcinogen Listing: (Ca) NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).
e) Skin Designation: Not Listed
f) Note(s): See Appendix A,

3) Listed as: Formalin (as formaldehyde)
4) REL:

5) IDLH:

a) IDLH: 20 ppm
b) Note(s): Ca

1) Ca: NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A).

C) Carcinogenicity Ratings for CAS50-00-0 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A2 ; Listed as: Formaldehyde

2) EPA (U.S. Environmental Protection Agency, 2011): B1 ; Listed as: Formaldehyde

a) B1 : Probable human carcinogen - based on limited evidence of carcinogenicity in humans.

3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Formaldehyde

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

5) NIOSH (National Institute for Occupational Safety and Health, 2007): Ca ; Listed as: Formalin (as formaldehyde)

a) Ca : NIOSH considers this substance to be a potential occupational carcinogen (See Appendix A in the NIOSH Pocket Guide to Chemical Hazards).

6) MAK (DFG, 2002): Category 4 ; Listed as: Formaldehyde

a) Category 4 : Substances with carcinogenic potential for which genotoxicity plays no or at most a minor part. No significant contribution to human cancer risk is expected provided the MAK value is observed. The classification is supported especially by evidence that increases in cellular proliferation or changes in cellular differentiation are important in the mode of action. To characterize the cancer risk, the manifold mechanisms contributing to carcinogenesis and their characteristic dose-time-response relationships are taken into consideration.

7) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS50-00-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Formaldehyde; see 29 CFR 1910.1048
2) Table Z-1 for Formaldehyde; see 29 CFR 1910.1048:

a) 8-hour TWA:

1) ppm:

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3:

a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.

3) Ceiling Value:
4) Skin Designation: No
5) Notation(s): Not Listed

3) Table Z-2 for Formaldehyde; see 1910.1048:

a) 8-hour TWA:
b) Acceptable Ceiling Concentration:
c) Acceptable Maximum Peak above the Ceiling Concentration for an 8-hour Shift:

1) Concentration:
2) Maximum Duration:

d) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) Lewis, 2000 Lewis 1992; OSHA, 2002c; RTECS, 2001)

1) LD50- (ORAL)MOUSE:

a) 42 mg/kg -- depressed activity, convulsions

2) LD50- (SUBCUTANEOUS)MOUSE:

a) 300 mg/kg -- pulmonary edema, bronchiolar constriction

3) LD50- (ORAL)RAT:

a) 100 mg/kg
b) 800 mg/kg (Lewis, 1992; OSHA, 2002c)

4) LD50- (SUBCUTANEOUS)RAT:

a) 420 mg/kg -- pulmonary edema, bronchiolar constriction

5) TCLo- (INHALATION)HUMAN:

a) 17 mg/m(3) for 30M -- eyes and pulmonary effects
b) 300 mcg/m(3) -- aggression, changes to sense organs

6) TCLo- (INHALATION)MOUSE:

a) 40 ppm for 6H/13W-Intermittent -- death

7) TCLo- (INHALATION)RAT:

a) Female, 500 mcg/m(3) for 4H at 1-19D of pregnancy -- musculoskeletal, behavioral abnormalities
b) Female, 50 mcg/m(3) for 4H at 1-19D of pregnancy -- reproductive effects (Lewis, 2000)
c) Female, 12 mcg/m(3) for 24H at 1-22D of pregnancy -- biochemical, metabolic changes in progeny
d) Female, 12 mcg/m(3) for 24H at 15D prior to mating and at 1-22D of pregnancy -- reduced weight gain in offspring
e) Female, 1 mg/m(3) for 24H at 1-22D of pregnancy -- cytological effects
f) 99 ppm for 6H/30 D -- metabolic, immunological and blood changes
g) 15 ppm for 6H/24W-Intermittent -- biochemical, metabolic and pulmonary changes
h) 3,200 ppb for 6H/3D-Intermittent -- biochemical, sensory organ changes
i) Male, 35 mcg/m(3) for 8H at 60D prior to mating -- paternal reproductive effects

Pharmacology Toxicology

Toxicologic Mechanism

Physicochemical

Physical Characteristics

Ph

Molecular Weight

Other

1) 0.8 ppm (CHRIS, 2001)
2) 0.83 ppm (reported range 0.05-1.0 ppm) (ACGIH, 1991)
3) OHM/TADS (2001) reports the following odor thresholds:

1) Lower: 0.8 ppm
2) Medium: 49.9 ppm
3) Upper: 102 ppm

4) Clayton & Clayton (1993) reports that most persons are able to detect formaldehyde at levels below 1 ppm; mild sensory irritation at 2-5 ppm; unpleasant at 5-10 ppm; and, intolerable at levels in excess of 25 ppm.
5) 20 ppm is quickly irritating to the eyes (Lewis, 2000).

1) 50 ppm (lower taste threshold) (OHM/TADS, 2001)

Animal Toxicology

References

General Bibliography

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FORMALDEHYDE

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Hematologic

Dermatologic

Immunologic

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Ph

Molecular Weight

Other

General Bibliography