A silent killer in the laboratory – Formaldehyde: Review of effects and management
Jayalakshmi K, Ravikumar H, Jaya Naidu, Raju Raghavendra
Despite the known toxicity of formaldehyde and its potential health effects, laboratory workers and others have little enthusiasm for reducing or replacing the formaldehyde working solution. The responsibility of preventing health hazards is by both management and laboratory workers. It is the responsibility of the laboratory workers to understand and adopt good laboratory practices to achieve a healthy environment. It is important to have good toxicological and inflammability profiles that permit the safe use of formaldehyde. The aim of this review is to summarize the various applications, potential hazards and management of formaldehyde effects in the laboratories.
Key words: Biohazards; Formaldehyde; Osha; Biological Waste Disposal; Pathological;
Jayalakshmi K, Ravikumar H, Jaya Naidu, Raju Raghavendra. A silent killer in the laboratory – Formaldehyde: Review of effects and management. International Journal of Oral & Maxillofacial Pathology; 2011:2(2):13-19. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved.
Received on: 22/03/2011 Accepted on: 11/06/2011
Communication standard is the Occupational Safety and Health Administration (OSHA) regulation that requires evaluation and communication to employees of all chemical hazards in the work place. OSHA and Centre for Disease Control and prevention (CDC) in 1970 gave safety regulations for clinical laboratories with numerous safety standards in a clinical set up.1 They insisted that each employee who works with or around hazardous chemicals must receive information about those chemicals through a comprehensive training program. Chemical manufacturers are required to evaluate product hazards and should alert customers. Those informed employees can more effectively participate in, and support the protective measures instituted in their workplaces. Hazard communication programs are also commonly referred to as “Right-to-know” programs.2
The OSHA Formaldehyde Standard was written to protect employees who came into contact with formaldehyde. The formaldehyde standard is in addition to the provisions of the hazard communication standard covering exposures to all hazardous chemicals or substances. The fact that formaldehyde is the subject of its own federal regulation should emphasize the need to protect employees from exposure.3
Formaldehyde is a flammable, colorless gas with a pungent, suffocating odor. It is highly soluble in water (up to 55%), acetone, benzene, chloroform, diethyl ether and ethanol. The gas is stable in the absence of water but it is incompatible with oxidizers, alkalis, acids, phenols and urea. Explosive reactions occur with peroxide, nitrogen oxide, and performic acid. Anhydrous gaseous formaldehyde is not available commercially.
Aldehyde groups are chemically and biologically reactive and are responsible for many histochemical reactions, e.g. free aldehyde groups may be responsible for argentaffin reactions. Pure formaldehyde is a vapor that when completely dissolved in water forms a solution containing 37-40% formaldehyde: this aqueous solution is known as „formalin‟, with 0.5% to 15% methanol as a polymerization inhibitor.2
Formaldehyde in its 10% neutral buffered form (NBF) is the most common fixative used in diagnostic pathology. The usual „10% formalin‟ used in fixation of tissues is a 10% solution of formalin, i.e., it contains about 4% weight to volume of formaldehyde. The reactions of formaldehyde with macromolecules are numerous complexes. In an aqueous solution formaldehyde forms methylene hydrate, a methylene glycol as the first step in fixation.4
Methylene hydrate reacts with several side chains of proteins to form reactive hydroxymethyl side groups (-CH2-OH).4 Formaldehyde also reacts with nuclear proteins and nucleic acids. It penetrates
between nucleic acids and proteins and stabilizes the nucleic acid – protein shell.4 Formaldehyde reacts with unsaturated lipids, but does not interact with carbohydrates. The side chains of peptides or proteins that are most reactive with methylene hydrate and hence have the highest affinity for formaldehyde including lysine, cysteine, histidine, arginine, tyrosine and reactive hydroxyl groups of serine and threonine. It was reported that one of the most important cross links in „over-fixation‟, i.e., in tanning, is that between lysine and the amide group of the protein back bone. Due to the shorter times of fixation of current diagnostic pathology and biological applications cross linking reactions with the protein backbone is unlikely.4
Worldwide production of Formaldehyde is over 16 billion pounds per year. 60% of all formaldehyde used in wood and construction related industries are as urea-formaldehyde, phenol-formaldehyde and melamine-formaldehyde glues, resins and stiffeners. 30% is used as a chemical intermediate (e.g. Pentaerythritol, hexamethylenetetramine, butanediol) to manufacture another chemical of commerce. 7% is used in thermoplastic resins. 2% used in textile / apparel industry as a whitener / finisher / stiffener for shirts. 1% or less is used as preservative additives in soaps, lotions, shampoo etc5,6 and also used in cosmetology. It is used to preserve animal specimens used in secondary school and college biopsy classes and also as a sterilant and tissue preservative. Embalmers use formaldehyde to preserve human remains for burial.7
According to a 1997 report by the U.S. Consumer product safety commission, formaldehyde is normally present in both indoor and outdoor air at low levels, usually less than 0.03 parts of formaldehyde per million parts of air (PPM). Materials containing formaldehyde can release formaldehyde gas or vapor into the air.8
Biohazards of Formaldehyde
Toxic actions of formaldehyde occur after gaseous formaldehyde has become dissolved in water – free gaseous formaldehyde does not exist in cells and to interact with cells covered with a film of water, such as the eyes, the formaldehyde must first dissolve. The rate of release of gaseous formaldehyde and the resultant depletion in solution is increased with agitation or heat. The gaseous formaldehyde in the solution reacts with chemicals, human hair or tissue with the same consequence. For this reason, the hazards associated with the use of a solution of formaldehyde are the same as the hazards of gaseous formaldehyde since the solution so readily releases gaseous formaldehyde.2
Formaldehyde has its own OSHA standard because it is so toxic. Formaldehyde is a sensitizing agent that can cause an immune system response upon initial exposure. It can be inhaled as a gas or vapor or absorbed through the skin as a liquid or by eye contact.3 Related to immunology, a study conducted by Dykewicz et al9 showed that clinical IgE- mediated allergy to gaseous formaldehyde does not exist, or if it does exist, it is extremely rare. Most people can detect the odor of formaldehyde at concentrations between 0.5 and 1.0 parts per million. Those people who become sensitized to formaldehyde may experience headaches and minor eye and airway irritation even at relatively low levels.2 The documented effects of formaldehyde includes eye, nose and throat irritation, loss of sense of smell, increased upper respiratory disease, dry and sore throats, respiratory tract irritation, cough, chest pain, shortness of breath and wheezing2,6,10 The National Institute for Occupational Safety and Health (NIOSH) cites many reports of primary skin irritation and allergic dermatitis as a result of skin contact with water solutions of formaldehyde. In the case of formaldehyde, the widespread exposure to the product at low levels heightens the concerns with regard to sensitization. The American Conference of Industrial Hygienists (ACGIH) notes that “there is a substantial portion of the population, comprising up to 20% for whom air borne formaldehyde at concentrations on the order of 0.25 to 0.5 ppm is troublesome” and that
is “it is plausible that a similar proportion (10% to 20%) who are more responsive may react acutely to formaldehyde at very low concentrations <0.25 ppm”.2
Adverse effects on the central nervous system such as increased headaches, depression, mood changes, insomnia, irritability, attention deficit, and impairment of dexterity, memory and equilibrium have been reported to result from long term exposure. Formaldehyde has been proven to cause birth defects in animals and is probably not likely to cause birth defects in humans at occupationally permissible levels. However special consideration regarding the exposure of pregnant women is warranted since formaldehyde has been shown to damage DNA.2
Concentrations of 100 parts formaldehyde per million parts air are immediately dangerous to health. Embalmers are exposed to formaldehyde at concentration averaging up to 9 parts per million (ppm) during the embalming process. The short term exposure of Formaldehyde at levels up to 5 ppm cause eye, nose, throat irritation and exposure at levels from 10 to 20 ppm causes coughing, chest tightness with irregular heartbeat. Long term exposure to low levels of formaldehyde may cause respiratory difficulty, eczema and sensitization.5 Exposures from 50 to 100 ppm cause fluid on the lungs, which later may cause death.
Formaldehyde as a carcinogen
Although the short-term health effects of formaldehyde exposure are well known, less is known about its potential long-term health effects. In 1980, laboratory studies showed that exposure to formaldehyde could cause nasal cancer in rats. This finding raised the question of whether formaldehyde exposure could also cause cancer in humans. In 1987, the U.S. Environmental protection Agency (EPA) classified formaldehyde as a probable human carcinogen under conditions of unusually high or prolonged exposures . Since that time some studies of humans have suggested that formaldehyde exposure is associated with certain types of cancer. The International agency for research on cancer (IARC) classifies formaldehyde as a human carcinogen.11
Formaldehyde undergoes rapid chemical changes immediately after absorption. The Environment Protection Agency (EPA) and the International Agency for research in cancer consider formaldehyde a probable carcinogen prompting the lower workplace limits suggested by the National Cancer Institute2,6,12,13 The most recent data on lung cancer from the cohort study did not find any relationship between formaldehyde exposure and lung cancer mortality.8
Formaldehyde in lympho-haemopoietic system
Several National Cancer Institute (NCI) surveys of professionals who are potentially exposed to formaldehyde in their work, such as anatomists and embalmers, have suggested that these individuals are at an increased risk of leukemia and brain cancer compared with the general population. However, specific work practices and exposures were not characterized in these studies. An NCI case-control study among funeral industry workers that characterized exposures to formaldehyde also found an association between increasing formaldehyde exposure and mortality from myeloid leukemia.14 This study was carried out among funeral industry workers who had died between 1960 and 1986. The researchers compared these workers who had died from hematopoietic, lymphatic cancers and brain tumors with those who died from other causes. This analysis showed that, those who had performed the most embalming and those with the highest estimated formaldehyde exposure had the greatest risk of myeloid leukemia. There was no association with other cancers of the hematopoietic and lymphatic systems or with brain cancer.
A number of cohort studies involving workers exposed to formaldehyde have recently been completed. One study, conducted by NCI, looked at 25,619 workers in industries with the potential for occupational formaldehyde exposure and estimated each workers exposure to the chemical while at work.15 The results showed increased risk of death due to leukemia, particularly myeloid leukemia, among workers exposed to formaldehyde. This risk was associated with increasing peak and average levels of exposure, as well as with the duration of exposure, but it was not associated with cumulative exposure. An additional 10 years of data on the same workers were used in a follow-up study published in 2009.12 This analysis continued to show a possible link between formaldehyde exposure and cancers of the
hematopoietic and lymphatic systems, particularly myeloid leukemia. As in the initial study, the risk was highest earlier in the follow-up period. Risk declined steadily over time, such that the cumulative excess risk of myeloid leukemia was no longer statistically significant at the end of the follow-up period. The researchers noted that similar patterns of risks over time had been seen for other agents known to cause leukemia.
A cohort study of 11,039 textile workers performed by the National Institute for occupational safety and health (NIOSH) also found an association between the duration of exposure to formaldehyde and leukemia deaths.16 However, the evidence remains mixed because of a cohort study of 14,014 British industry workers found no association between formaldehyde exposure and leukemia deaths.17
Management of Formaldehyde Related Health Hazards
Increasing awareness of the health hazards associated with chemicals commonly used in Anatomy, Histology departments has stimulated both equipment manufacturers and medical laboratory scientists to improve the laboratory environment by reducing the release of toxic fumes. Closed circuit tissue processors and the absorption of fumes by charcoal filters are both examples of developments by manufacturers. The efficiency of removal of the formaldehyde and xylene was measured using infrared spectroscopy.19 Chemicals used to fix specimens that are purchased for dissection are notorious for the dangers they pose to human health. Dissections that are carried out over a period of months lead to conditions that promote desiccation and degeneration of the specimens. The problem of students working with important but potentially harmful materials is not a new one.
Similar situations exist in the dissection labs of medical schools and other student labs where many hours are spent dissecting fixed material.20 The use of a formaldehyde neutralizing spray each time students work on their specimens and the use of 2% phenoxy-ethanol results in greatly improved air quality in the dissection laboratory. The improved work conditions will allow students to concentrate on their dissections and the fascinating anatomical configurations that form the core of any course in comparative vertebrate anatomy.21
Management of Acute Exposure to Formaldehyde
This includes showers, eyewash stations if contact with eye occurs. Use of antihistamines and bronchodilators are advised if Asthma like symptoms exists. When airborne concentrations exceed allowable limits, respirators must be used.
Chemical manufacturers are required to evaluate product hazards and to alert customers to those hazards through containers labels, Material Safety Data Sheets (MSDS) and Customers Support.3 Information that must be listed on the MSDS includes (but is not limited to):
- The Permissible Exposure Limit (PEL) established by OSHA, the Threshold Limit Values (TLV) and any other recommended exposure limits identified by the manufacturer, importer, or distributor
- All health effects including acute and chronic side effects, carcinogenicity and sensitization
- All precautions for safe handling and use, including protective equipment, engineering controls, and work practice controls.
- First aid and emergency procedures
In addition to meeting these hazard communication requirements, the formaldehyde standard requires employers using materials above the 0.1% threshold to assess actual airborne exposures, as well as to meet other requirements related to personal protective equipment and emergency eyewash depending upon the exact hazards involved.2
Monitoring of exposure limits
Monitoring is required unless it can be objectively documented that the operation cannot result in concentrations above the OSHA action level (0.5ppm). The exposure limits for formaldehyde has been tabulated in Table 1.
Formaldehyde protection program3
This program includes
- How labels and other forms of warning are used at your facility regarding formaldehyde hazards
- How the hazards of formaldehyde are communicated to employees
- The specifics of your employee formaldehyde safety training program
Average outdoor level
Recommended upper limit for residences by ASHRAE, ANSI, EPA
NIOSH recommended upper limit for15 minutes exposure in workplace
NIOSH recommended upper limit for 10-day-average exposure in workplace
Recommended upper limit for manufactured homes
OSHA workplace limit
OSHA 8-hour exposure limit
Level at which most people first detect odor
Table.1, Formaldehyde Exposure limits (John Wiley and Sons, 2000, Best Practices Guide to Residential Construction.6)
Personal Protective Equipment (PPE)
This is applied when engineering and work practice controls cannot reduce and maintain employee exposure to formaldehyde. When the potential for skin and eye contact with formaldehyde exists, impervious clothing, gloves, aprons and chemical goggles must be worn. Showers and eyewash stations must be provided if splashing is likely. If the allowable limits exceeds then respirators must be used.3
In addition to the applicable training requirements for hazard communication, personal working with formaldehyde must receive annual chemical-specific information and training on their job assignment.3
This should be provided for personnel who are exposed to airborne formaldehyde at high concentrations.3
Engineering controls include enclosing and / or providing appropriate ventilation systems for operations.3
Alternatives to Formaldehyde
With the use of aldehydes becoming increasingly unacceptable throughout the world due to efficacy and safety issues, many alternate chemical solutions was employed.
The H2O2 gassing technology
The latest development in H2O2 gassing technology for the routine and emergency decontamination of enclosures has an advantage over using formaldehyde. Hydrogen peroxide vapor (H2O2) is non-carcinogenic, safe and efficacious against a wide range of viruses, bacteria and moulds offering clear advantages over other techniques, such as formaldehyde, peracetic acid fogging or the nebulizing of toxic biocides. H2O2 vapor breaks down under catalytic action making it environment friendly, leaving no residues unlike many other biocides.22 The disadvantage of using this technique is time consuming and it is expensive.
A combination of propylene glycol, ethylene glycol, phenyl ether and phenol can be used. Another alternative is primarily gluteraldehyde and also a mixture of diazolidinyl urea, 2-bromo-2-nitropropane-1, 3-diol (Bronopol), zinc sulfate, and sodium citrate could be used. Different species may be preserved in different solutions by the same company. All alternatives should match or exceed the important technical and performance criteria for educational specimens such as the color, texture, and stiffness of the specimen tissue. The color of the alternative specimens was as good as or better than the formalin preserved specimen.7
Formaldehyde storage and waste disposal
Formaldehyde products must be stored in a cool, well ventilated area, and in accordance with any additional requirements listed on the MSDS. Label all mixtures or solutions composed of greater than 0.1 ppm. For all materials capable of releasing formaldehyde at levels above 0.5 ppm during normal use, the label must contain the words “potential cancer hazard”. Waste formaldehyde products must be stored in a labeled hazardous waste container for proper disposal, or made available for recycling, if practical.
Exposure to formaldehyde is toxic and can produce various health problems. Safety awareness should become habit and a way of life in the laboratory. Safety is an important aspect of any clinical laboratory. An employer is required by law to take preventive measures to protect employees from formaldehyde protective program.3 It is the employer‟s responsibility to select, provide and maintain personal equipment.3
Hazardous substances from the histology/ anatomy laboratories cannot be removed entirely, but can be reduced sufficiently to lessen the risks to health.
1. Dr. Jayalakshmi K, Associate Professor, Department of Oral Pathology and Microbiology. 2. Dr. Ravikumar H, Assistant Professor, Department of General Surgery. 3. Dr. Jaya Naidu, Professor, Department of Pedodontics, Vydehi Institute of Dental Sciences & Research Centre, Bangalore, India. 4. Dr. Raju Raghavendra, Reader, Department of Oral Pathology & Microbiology, Peoples Academy of Dental Sciences, Bhopal, India.
All the Staff Members in the Department of Oral Pathology, Vydehi Institute of Dental Sciences & Research Centre, Bangalore, Karnataka, India.
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Dr. Jayalakshmi. K,
Department of Oral Pathology & Microbiology,
Vydehi Institute of Dental Sciences & Research Centre, Bangalore.
Ph: +91 9972232066
Email id: firstname.lastname@example.org
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