Month: May 2025

The Real Scoop on Formaldehyde

If formaldehyde is so dangerous, then why is it still used in the laboratory today? It is so dangerous, in fact, that the United States Occupational Safety and Hazard Administration (OSHA) has a standard for the chemical, OSHA Formaldehyde standard (29 CFR 1910.1048). However, despite its dangers, formalin is still the best product available with the most tolerable risk for the needs we have in the lab.  

Anatomic pathology has faced the great challenge of tissue preservation for hundreds of years. Decomposition, degradation from microbiological contamination, and even optimal hydration have hindered the proper isolation and study of tissue and organs. Early fixatives such as picric acid, osmium tetroxide, and even mercuric chloride were excellent at preserving the samples, but these compounds are extremely toxic and/or volatile. It wasn’t until 1893 when a German physician named Ferdinand Blum discovered the benefits of formaldehyde. Blum concluded that immersion of tissues in a 4% solution of formaldehyde, the 10% neutral buffered formalin widely used today, provided excellent preservation with a much lower risk to the user.

How dangerous is formalin? Keeping formalin off your skin and out of your eyes is crucial since it is a tissue fixative. An even greater risk of working with formalin comes from its respiratory hazards. Formalin off-gases quickly, creating a very dangerous, and unseen hazard. When inhaled, formalin can cause difficulty breathing, coughing, and wheezing. In addition, long-term exposure can cause respiratory issues, skin irritation, and an increased risk of nasopharyngeal cancer, formaldehyde is a known carcinogen.

Baseline exposure monitoring is required by OSHA to demonstrate that employees are not overexposed while working with and around formalin. Badge readings that fall below the time weighted average (TWA) of 0.75 ppm over an eight-hour period or below the short-term exposure limit (SEL) of 2 ppm over a 15-minute period, prove that the lab is a safe environment and additional badge monitoring is not required. However, if the readings exceed the limits, or if changes to the lab or processes are made, subsequent badge monitoring should be performed.  

How can the lab control for exposures to the chemical? The best practice is to limit the time staff work with open containers of formalin. Of course, this is not always possible. Therefore, respirators, chemical fume hoods (CFH), grossing hoods, and room ventilation may be necessary. Keeping equipment in good running condition helps to minimize exposure. Therefore, grossing hoods and the CFH should be certified annually, and staff should undergo fit testing for respirators each year as well.

When it comes to hazardous waste, laboratories have several options for removing formalin from the premises.  Anatomic pathology labs are required to dispose of both solid and liquid waste, two separate waste streams.  Solids can go out as regulated medical waste with proper labeling, but what the liquid waste must be handled differently. Labs can either neutralize the waste onsite or contract with a vendor to have it removed. Organizations can neutralize formalin waste on-site for disposal in their normal sewage system. This does mean, however, that labs need to monitor their neutralization process which includes pH and aldehyde testing of the waste prior to pouring down the drain. It is always recommended to confirm this process with local wastewater treatment centers to ensure the proper steps are being taken prior to disposing of the waste.

Unbuffered formalin can break down quickly, but buffered formalin has a limited shelf life. Therefore, limiting the quantity on hand in the lab not only helps with product quality, it also keeps staff safer. Another good lab practice is to limit the height at which formalin is stored. As with all corrosive chemicals in the department, formalin should be stored below shoulder height. Do you store your formalin in a flammable cabinet? Formaldehyde, the active ingredient in formalin, is a flammable gas. However, only solutions with higher concentrations of formaldehyde are actually listed as flammable. A container of 37% formaldehyde is considered flammable, but 10% NBF is stable under normal conditions and classified as non-flammable. 

Chemical spills happen, so departments need to be ready to respond to such an event. A formalin spill in the lab or the operating room cab be dangerous to staff and patients. Knowing how to handle the spill can be the difference between a safe response or an event that causes staff and/or patients harm. As stated, formalin gives off a gas, so placing an absorbent mat or a towel on a spill will only increase the surface area that can generate harmful gases. Therefore, having a neutralizing product available for spills and training staff to use the product is essential. Staff that run through spill drills frequently know the location and contents of their spill kits and respond more effectively.   Working with formalin is dangerous, but the more staff know about the product and respect it, the safer their work practices become. Using and keeping formalin in the lab requires some planning and training. The lab is a dynamic environment, so workspaces and procedures should be reviewed often. Train staff on formalin safety and help them to always work safely with formalin.

-Jason P. Nagy, PhD, MLS(ASCP)CM is a Lab Safety Coordinator for Sentara Healthcare, a hospital system with laboratories throughout Virginia and North Carolina. He is an experienced Technical Specialist with a background in biotechnology, molecular biology, clinical labs, and most recently, a focus in laboratory safety.

Microbiology Case Study: A Middle-Aged Male with Altered Mental Status

Case presentation

A middle-aged male with a history of type 2 diabetes, hypertension, obesity, and alcohol-related cirrhosis presented to the emergency department with altered mental status. He was obtunded, acutely encephalopathic and hypoglycemic. He soon developed emesis and coded during clinical assessment, undergoing emergent intubation. He was found to be profoundly acidotic with labs consistent with disseminated intravascular coagulation and multiorgan failure. The patient was transfused but continued to code multiple times before and during ICU transfer/admission. Despite multiple resuscitation attempts, he expired soon afterwords.

Laboratory workup

Blood cultures drawn in the ED prior to admission became positive with curved gram-negative rods (Image 1A) within 16 hours. An oxidase-positive, indole-positive, beta-hemolytic organism was recovered after 24 hours of incubation. The organism was lactose-fermenting (confirmed by ONPG) and exhibited colorless growth on Thiosulfate Citrate Bile Salts agar suggestive of a lack of sucrose utilization (Image 1B, set up for demonstrative purposes). The organism was definitively identified as Vibrio vulnificus by MALDI-TOF MS. No additional workup was undertaken as the patient had expired prior to the organism being recovered from blood culture.

Image 1.  A: Gram stain from a positive blood bottle revealing curve gram-negative rods (100X magnification). Inset demonstrates the morphologically distinct curved appearance.  B: Blood and TCBS agars revealing growth of V. vulnificus. Lack of yellow colorization on TCBS media indicates lack of sucrose utilization. Biochemical testing revealed oxidase, catalase, and indole positivity also consistent with the MALDI-TOF identification of V. vulnificius.

Discussion

Vibrio sp. are marine bacteria that naturally colonize brackish and saltwater aquatic environments. Of the more than 70 currently recognized species, at least 12 are recognized as human pathogens.1 Human infections are broadly classified as being either cholera (caused by V. cholerae) or vibriosis (caused by other non-V. cholerae Vibrio spp.). Unlike cholera; a severe diarrheal illness usually acquired through ingestion of contaminated food or water, vibriosis represents a group of infections with varied clinical manifestations dependent upon the etiologic agent, route of infection, and host susceptibility.2 Non-cholera vibrios are often found in seawater with moderate to high salinity and as clinically important contaminants of raw or undercooked seafood.

                V. vulnificus thrives in warmer water and infections follow a seasonality, peaking in the warmer summer months.3 In contrast to V. cholerae and V. parahaemolyticus, V. vulnificus infections generally are associated with patients with underlying conditions, most commonly diabetes, liver disease and iron storage disorders. It is estimated that patients with chronic liver diseases (particularly cirrhosis due to either alcoholism or chronic hepatitis B or C) are 80-fold more likely to develop V. vulnificus-associated primary septicemia than healthy counterparts.2 Infections are most common in men aged 45-60 years who make up 85-90% of patients,4 consistent with this case. Contaminated food consumption (particularly filter feeding shellfish) can result in gastroenteritis or primary septicemia and disseminated disease.

Non-cholera vibrios are estimated to cause up to 80,000 infections worldwide, with V. parahaemolyicus and V. alginolyticus responsible for most cases. Among this group of organisms, V. vulnificus stands out as being particularly virulent; between 150-200 V. vulnificus infections are reported to the US CDC annually, with 20% being fatal.5 This organism oftencauses more than 95% of seafood-related deaths in the United States and the highest case fatality of any foodborne pathogen [2]. V. vulnificus also causes serious skin/soft tissue infections. This can occur either through exposure of a preexisting wound to contaminated seawater, or through injury while handling contaminated seafood. Cutaneous infections can present as cellulitis or bullae, which can progress to necrotizing disease and secondary sepsis is left untreated.6

No epidemiological link was able to be established between this patient’s case and either seafood or exposure to seawater, although cases of V. vulnificus infections among patients without classical exposure risk has been documented.7 This case of V. vulnificus primary septicemia highlights the acuity of this presentation as well as the importance of including V. vulnificus in differential diagnosis of hosts with associated risk factors and/or epidemiological links. Blood culture remains the gold standard for diagnosis. Importantly, doxycycline in combination with a third-generation cephalosporin constitutes the standard regimen for antibiotic therapy – however, doxycycline is not usually considered a first-line antibiotic for management of patient with gram-negative bloodstream infections, so rapid and accurate identification of V. vulnificus in this setting is essential.

1.           Kokashvili, T., et al., Occurrence and Diversity of Clinically Important Vibrio Species in the Aquatic Environment of Georgia. Front Public Health, 2015. 3: p. 232.

2.           Baker-Austin, C., et al., Vibrio spp. infections. Nature Reviews Disease Primers, 2018. 4(1): p. 1-19.

3.           Hughes, M.J., et al., Notes from the Field: Severe Vibrio vulnificus Infections During Heat Waves – Three Eastern U.S. States, July-August 2023. MMWR Morb Mortal Wkly Rep, 2024. 73(4): p. 84-85.

4.           Jones, M.K. and J.D. Oliver, Vibrio vulnificus: disease and pathogenesis. Infect Immun, 2009. 77(5): p. 1723-33.

5.           Bharathan, A., et al., Implication of environmental factors on the pathogenicity of Vibrio vulnificus: Insights into gene activation and disease outbreak. Microb Pathog, 2025. 204: p. 107591.

6.           Coerdt, K.M. and A. Khachemoune, Vibrio vulnificus: Review of Mild to Life-threatening Skin Infections. Cutis, 2021. 107(2): p. E12-e17.

7.           Candelli, M., et al., Vibrio vulnificus—A Review with a Special Focus on Sepsis. Microorganisms, 2025. 13(1): p. 128.

-Rene Bulnes, MD is an Infectious Diseases Clinician and current Medical Microbiology Fellow at the University of Texas Southwestern Medical enter in Dallas, TX.

-Andrew Clark, PhD, D(ABMM) is an Assistant Professor at the Johns Hopkins University School of Medicine in the Department of Pathology, and Director of the Bacteriology Laboratory at the Johns Hopkins Hospital. He completed a CPEP-accredited postdoctoral fellowship in Medical and Public Health Microbiology at National Institutes of Health, and is interested in the molecular mechanisms of antimicrobial resistance, susceptibility testing, and the evaluation of novel technology for the clinical microbiology laboratory.