Definition/Introduction

The Occupational Safety and Health Administration (OSHA) is a branch of the United States Department of Labor that oversees and enforces standard workplace conditions to minimize workplace health and safety risks. In addition to setting and overseeing workplace standards, OSHA also provides additional education and outreach to high-risk fields, including healthcare.

While OSHA sets general standards that transcend nearly all fields of work, many specific regulations pertaining to the healthcare field are in place including, but not limited to, bloodborne pathogens, harmful chemicals, infectious diseases, and personal protective equipment necessary to prevent exposure of individuals to hazardous materials/organisms. One such potentially hazardous chemical is formaldehyde, a colorless gas with a strong, distinct smell that is the most commonly used tissue preservative and fixation product in pathology and anatomy laboratory settings in the United States.[1][2][3]

Outside of the healthcare field, formaldehyde is commonly found in household products, glues, plywood, fabrics, paper products, and industrial cleaning solutions. Regulated via under standard 29 CFR 1910.1048, formaldehyde safety is enforced by OSHA to mitigate the potentially harmful effects of acute and chronic exposure to the gas, vapor, liquid, or solution (formalin) states of formaldehyde.

Issues of Concern

Before OSHA regulations in the United States within the workplace, an average of 38 work-related deaths occurred daily, or nearly 14,000 deaths annually. Today, the rate of work-related deaths has decreased to just 14 per day despite a significantly larger workforce.[4]

Despite the strides made by OSHA regulations toward complete safety in the workplace, accidents do still occur and account for roughly 5,000 work-related deaths per year currently. The workplace can be particularly dangerous for professionals whose job description entails working in a potentially harmful situation, such as those exposed to formaldehyde.

Formaldehyde is of concern, given its implications on the health of those exposed to it. Common exposure places to this hazardous chemical include biopsy immersion, sample registration, and gross anatomy labs. Monitoring exposure levels requires devices specifically designed to measure the concentration of formaldehyde in the air. OSHA guidelines state that the permissible exposure limit (PEL), or the highest allowable exposure dose, for formaldehyde, including its gas and solution forms, in the workplace is 0.75 parts formaldehyde per million parts of air (ppm) which is calculated as a weighted average over an 8-hour timeframe.

For short-term exposures, the PEL is two ppm over 15 minutes. Additionally, the threshold for increased monitoring and initiating medical surveillance of workers is 0.5 ppm over 8 hours. Daily use of devices to measure formaldehyde concentration would be necessary to prevent overexposure. However, this may not be standard practice in many laboratories as no single device has emerged as the standard real-time detection method.

Some devices or techniques that can be used to detect formaldehyde levels include:

1. Photometry utilizes the yellow absorbance pattern produced by the reaction with formaldehyde in the air and beta-diketone and can detect concentrations between 0.005 to 5 ppm every 3 minutes to 2 hours.
2. Fluorimetry utilizes gaseous formaldehyde trapped in an aqueous solution within a stripping coil, allowing the measurement of formaldehyde levels between 0.001 to 3 ppm every 2 seconds to 2 minutes.
3. Electrochemical oxidation, the most commercially available measurement technique, utilizes a metal electrocatalyst and measures concentrations of oxidized formaldehyde as low as .005 ppm.
4. Infrared spectroscopy utilizes infrared light to induce chemical vibration patterns that are unique to the chemical structure of a molecule. This technique can detect concentrations between .001 to 10 ppm.
5. Cavity ring-down spectroscopy utilizes a laser shined into highly reflective mirrors to measure absolute optical extinction based on the scatter and absorption of light in aerosol samples. The technique can determine formaldehyde levels within seconds at concentrations at or less than .001 ppm.
6. Mass spectrometry ionizes formaldehyde molecules to create a mass-to-charge ratio that can be used to quantify the abundance of formaldehyde in a sample within 2 seconds at concentrations between .007 to 4 ppm.[5]

Despite multiple options, no technique is widely used in pathology laboratories to put employees at risk for adverse events without being aware of the problem. The significance of this problem is highlighted by a study that showed the ambient formaldehyde concentration in a gross anatomy lab was between 0.23 to 1.03 ppm, and individual exposure concentrations ranged from 0.45-1.08 ppm during a single session.[6]

To combat formaldehyde exposure and its associated complications, OSHA has established standards for employers to follow to maximize worker safety, including:

1. Initial monitoring to determine which employees may be at or above the standard exposure limits mentioned previously.
2. Implement practical controls that will reduce the worker exposure or provide respirators.
3. Label all solutions containing over 0.1% formaldehyde and materials releasing formaldehyde concentrations over 0.1 ppm as hazardous.
4. Label any materials releasing formaldehyde concentrations over 0.5 ppm as a potential cancer hazard.
5. Train any employee who may be exposed to over 0.1 ppm when beginning the position and when new formaldehyde sources are placed in the workplace. This training should be repeated annually.
6. Providing appropriate personal protective equipment to prevent skin and eye contacts
7. Provide stations to wash off formaldehyde splashes.
8. Provide medical surveillance for workers exposed to formaldehyde for signs and symptoms of overexposure.

Additionally, many approaches have been developed to reduce further exposure, including working in ventilated fume hoods and supplemental ventilation systems, using absorbent materials to collect excess formalin from tissues, using formaldehyde neutralizing kits for formaldehyde neutralizing kits spills, and placing tissue samples in containers pre-filled with formaldehyde.[5] Recent studies have shown that such interventions can reduce formaldehyde exposure greatly and subsequently minimize the risk of adverse reactions through continued investigation is necessary.[7][8][9]

The container that holds the formaldehyde in a clinical laboratory should also follow OSHA guidelines. Their guidelines suggest that any container holding either formaldehyde or material that releases formaldehyde should be labeled as such if levels released into the air are more significant than 0.1 ppm. Further, anything that can release over 0.5 ppm into the air should be labeled as containing formaldehyde and also as a respiratory sensitizing agent and carcinogen.

Clinical Significance

There is a linear relationship between the relative amount of formaldehyde exposure and the severity of potential side effects. People may experience various symptoms upon first exposure, including eye irritation, upper airway irritation with coughing, wheezing, chest pain, bronchitis, and allergic skin reactions. However, many people may not experience any side effects at all during the first exposure. The irritation of the eyes and nose is attributed to activation of cation channels of the transient receptor potential gene superfamily in the trigeminal nerve via covalent binding to cysteine residues on the channel.[10]

Though the allergic reaction may suggest the role of IgE, it has previously been shown that formaldehyde exposure does not induce IgE production but rather has been hypothesized to induce inflammation and act as an adjuvant for other allergens.[10] Formaldehyde is also well-known to be a sensitizing agent, so that subsequent exposures may pose an increased risk of allergic reactions to formaldehyde, including asthma and contact dermatitis.[11][12]

Asthmatic patients are especially prone to acute exacerbations when exposed to formaldehyde.[12] Despite the local irritation caused by inhalation, it is not likely that formaldehyde can reach internal organs by inhalation alone.[10][13]

Chronic contact with formaldehyde poses additional health risks beyond the irritation and allergic reactions of short-term exposures. The most worrisome risk is that formaldehyde is considered a carcinogen for both animals and humans and is classified as a Group 1 carcinogen by the International Agency for Research on Cancer.[14][15][16]

The carcinogenicity is multifactorial but is commonly attributed to the direct genotoxicity observed during in vitro and in vivo studies and DNA damage, formation of micronuclei exchanges of sister chromatids, and other chromosomal abnormalities in both the lymphocytes and nasal mucosa cells of people with occupational exposure to formaldehyde.[13]

The most common cancers linked to formaldehyde exposure are nasopharyngeal cancers which implicate inhalation as the likely predisposing mechanism as formaldehyde is water-soluble and highly reactive, thus allowing it to be retained in the nasal mucosa upon inhalation.[15][10]

Recent reports have shown an increased risk of leukemia and Hodgkin lymphoma with formaldehyde exposure, each having a dose-dependent relationship.[17][18][19] It has been speculated that this risk occurs via direct damage to stem cells in the bone marrow through the blood, damage to hematopoietic stem/progenitor cells circulating in the blood, and damage to primitive pluripotent stem cells present within nasal or oral passages.[13]

Cardiovascular disease is also linked to formaldehyde exposure like lymphocyte-derived myeloperoxidase interacting with formaldehyde during myocardial infarction, direct contact with the sinus node, which can induce arrhythmias, and formaldehyde produced by semicarbazide-sensitive amine oxidase, like in diabetic patients, causing endothelial cell damage and increasing the risk for atherosclerosis, stroke, congestive heart failure, and death.[20] 

Other diseases that have recently been linked to formaldehyde exposure include neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.[21][22][23] The pathogenesis is yet to be fully elucidated, but epigenetic changes likely play a significant role.[21]

Nursing, Allied Health, and Interprofessional Team Interventions

Formaldehyde Exposure Prevention

Environmental exposure to formaldehyde is minimal, so workplace exposure is the primary source of concern regarding formaldehyde. All workplaces should take steps laid out by OSHA, including limiting exposure and monitoring for symptoms of overexposure, monitoring formaldehyde concentrations workers are exposed to, placing clear warnings on formaldehyde-containing materials, and providing appropriate personal protective equipment. All team members should continually monitor that these required workplace conditions are being maintained and bring them to the attention of appropriate administrators should they be compromised.

Specific to the healthcare setting in clinical pathology and gross anatomy laboratories, appropriate handling of formalin and other formaldehyde-containing solutions should be maintained. Personal protective equipment should always be worn to limit exposure. Additional steps like supplemental ventilation systems and pre-filled containers to place tissue samples in may be implemented to reduce exposure beyond that of standard practices further. Through these practices, healthcare team members like laboratory technicians and all workers handling formaldehyde can minimize the risk of adverse events associated with formaldehyde exposure.

Nursing, Allied Health, and Interprofessional Team Monitoring

Formaldehyde Exposure Management

Formaldehyde exposure management requires interprofessional collaboration to manage this patient population. While there is no antidote for acute overexposure to formaldehyde, symptomatic treatment of these patients is the standard of care. In the case of formaldehyde-induced acute allergic asthma reaction, the specialties of nursing, pharmacy, medicine, and social work all play a role in managing the patient.[12] [Level 1]

Nurses are critical in the initial evaluation and continuous monitoring of the patient’s condition. Clinicians and pharmacists should ensure that appropriate pharmacologic interventions are chosen and administered based on the patient’s condition. Inpatient internal medicine physicians and physician assistants should collaborate in the workup and diagnosis and continue monitoring the patient as they recover. Social work would play a role in addressing the source of formaldehyde exposure. A patient with potential formaldehyde-induced leukemia would involve similar interprofessional collaboration with the addition of radiologists and radiology technicians, oncologists, surgical teams, pathologists, and laboratory technicians in the workup, diagnosis, and treatment of such patients.[17][24]  [Level 4]

The best management of formaldehyde exposure is primary prevention. While minimal exposure is intrinsic to the job description of a healthcare team member working in clinical pathology or gross anatomy laboratory, safety techniques laid out by OSHA and supplemental modalities can reduce exposure and, given the dose-dependent relationship of formaldehyde and adverse events, subsequently minimize health risks.[8][7] [Level 3]

Formaldehyde is a commonly used substance in healthcare and industrial workplaces. Exposure can cause harmful side effects and potentially deadly diseases, so strict adherence to OSHA guidelines for formaldehyde safety is critical for the safety of all exposed to the substance.