Formaldehyde Exposure Safety Rationale

Let us discuss formaldehyde/ formalin’s physical and chemical features as far as safety issues are concerned. This background can help comprehend some prevention measures of its harmful effects. While using formalin, the appropriate working practices include minimizing formaldehyde evaporation as the safety rationale. The main point is that the surgical pathology laboratory practice uses 10% formalin, but not emanating gas formaldehyde which is what all physical and chemical laws in place regarding exposure are concerned with.

There are two aspects of formaldehyde’s exposure: local at the place of the initial contact (respiratory and digestive tracts, skin, etc.) and general as a result of absorption.  More than 90% of inhaled formaldehyde is absorbed in the upper respiratory tract and mixes with the endogenous formaldehyde pool. Endogenously produced, formaldehyde is a metabolic intermediate in all cells. The endogenous concentration of formaldehyde in human blood does not increase (2.77 microgram/gram) after inhalation for 40 minutes of 1.9 ppm formaldehyde. Because of its rapid metabolism in erythrocytes, no increase in tissue concentration of formaldehyde is detectable even moments after exposure.1  Absorbed formaldehyde can be oxidized to formate and exhaled as carbon dioxide. This data suggest that local exposure has the most significance from the safety approach.

Formaldehyde HCHO, a colorless gas, is rarely found in its original state because it had a short half-life in air due to its decomposition in light. Formaldehyde (methanal) is manufactured as a product of catalytic oxidation of methanol (CHOH). The concentrated water solution (37%-40%) of formaldehyde is called Formalin by its German trade name. The anatomical pathology practice uses Neutral Buffered Formalin (NBF) to prevent acidification due to formaldehyde’s tendency to be oxidized to formic acid. The buffer solution also enhances formation monomeric formaldehyde (methylene hydrate), as a fixation reagent. Methanol (7-10%) is added to prevent polymerization in paraformaldehyde.2

As a small light molecule, formaldehyde evaporates easily from the formalin surface. The kinetic energy of evaporation depends on temperature, humidity, and air flow.3 The thinner the layer of the liquid where formaldehyde is dissolved, the easier formaldehyde molecules can overcome the intermolecular boundaries, including Van der Waals force, and escape to gas phase. The kinetic theory also explains the well- known observation that evaporation depends on the temperature, the higher the more intensive. Everyone who had to open a working VIP processor during formalin phase can remember irritation of eyes and throat. Another condition that determines evaporation is humidity of the space, or water vapor. Humidity, as it is well known from our everyday life, prevents evaporation, and thus limits formaldehyde gas escape from liquid phase. Air flow increases escaping of formaldehyde of the formalin surface as well. Physics of formaldehyde gas should be in consideration in organization of laboratory working place and in emergencies of formalin spills.

As far as safety considerations are concerned, some chemical features of formaldehyde behavior in water solution (formalin) are important to discuss. Formaldehyde in water forms methylene glycol (methylene hydrate). The equilibrium between methilene glycol and formaldehyde in water solution lies in favor of methylene glycol. Formaldehyde requires conversion from methylene glycol to be able for actual covalent chemical reaction. This feature has a well known, especially to histotechlogists, name as fixation. Formaldehyde behaves as a fast penetrating, but slow fixative. Fast penetration is due to diffusion of methylene glycol. The slow fixative feature depends on covalent chemical reaction of carbonyl formaldehyde with proteins, glycoproteins, nucleic acids, and polysaccharids for intra-and intermolecular cross-linking of macromolecules. Slow fixation rate is positive from safety perspective because it buys time for formaldehyde elimination from upper respiratory and digestive tracts before the fixation damage is done. Formaldehyde’s high solubility in water causes fast absorption in mucus of the upper respiratory tract, predominately in nose cavity and sinuses. Mucus blanket is the first line of the body’s defense in formaldehyde exposure. This issue will be discussed more detailed in preventive measures section.

The physical and chemical characteristics of formalin are presented in some detail to provide a background for safety considerations. Safety concerns can be breaking up in three unequal groups: carcinogenicity, general medical problems, and acute harmful effect.

Some anatomy and physiology data relevant to formaldehyde exposure in laboratory practice might support understanding of damage prevention methods. They should be considered in connection with physical and chemical features of formalin.

The nasal mucosa of the lateral, inferior and medial walls of the nose, paranasal sinuses, and conches is covered with ciliated pseudostratified, columnar epithelium whose cilia form a carpet on which dust settles. The vibration of the cilia in the direction of the conches drives out the settled dust. The mucous membrane contains mucous glands (Goblet cells) whose secretions produces mucus 1 liter per day. It wraps around the dust and makes its expulsion easier and also humidifies the air. The mucous blanket, which is mowed by the cilia, flows to the sinus ostia and then to the nasopharynx where it is expectorated or swallowed. Serous glands within the lamina propria, deep to the mucous membrane, contribute fluid to the thinner periciliary layer of the blanket.

Water is 97% of mucus. Formaldehyde has absolute solubility in water. Formaldehyde is diluted and absorbed. It does not reach the pharynx under non extreme exposure. However, formaldehyde can damage the cilia, the most vulnerable structures. All preventive measures should be concentrating on minimizing this damage. Histotechnology needs fixation as a form of cellular and tissue preservation, but our body objects fixation as a way of our self-preservation.

Just a story. A small shiny toy bell was hanging near the grossing station. It lost the shiny appearance during five or six years.



What about our upper respiratory tract?


1. Heck HD, Casanova-Schmitz M, Dodd PB, et al. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CH2O under controlled conditions.  AmIndHyg Assoc J (1985) 46:1-3

2. Kiernan JA Histological and Histochemical Methods, 2008, 4th ed.Oxford: Butterworth-Heimann.

3. Giancoli DC: Physics. Principles with Application, 1998, Fifth Ed. Prentice Hall, pp 405-408








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