Dichloromethane
DichloromethaneÌý(DCM or methylene chloride) is aÌýcolorless, volatile liquid with a sweet odor.â€� It is widely used in a variety of commercial applications, including paint and coating removal products, adhesives, sealants, and automotive products.
In the chemical laboratory, DCM is often used as a solvent for chromatography and as a reaction medium, due to its polarity, low boiling point and low flammability.
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Industrial Uses of DCM:
- Paints & coatings
- Adhesives
- Sealants
- Automotive products
Laboratory Uses of DCM:
- Reaction solventÌý
- ChromatographyÌý
- Cleaning solventÌý
- Extraction solventÌýÌý
- Analysis chemical
Key Physicochemical Properties:
- Formula:ÌýCH2Cl2
- Molar Mass:Ìý84.93 g/mol
- Boiling Point:Ìý40 °C
- Water Solubility:Ìý13 g/L
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View the of DCM.
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What are the Health Hazards of DCM?
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Dichloromethane (DCM), like many volatile organic compounds (VOCs), poses health risks, but it is of particular concern due to its high bioavailability and metabolism into reactive intermediates such as formaldehyde and carbon monoxide. This metabolic activation significantly contributes to its toxicity and carcinogenic potential. DCM exposure has been classified as carcinogenic to humans, primarily based on its ability to induce tumors in multiple animal species and epidemiological evidence in exposed human populations (IARC, 2017).
Acute exposure to elevated levels of DCM can rapidly induce central nervous system depression. Initial symptoms often include dizziness and nausea, progressing rapidly to loss of consciousness or even death due to respiratory failure or cardiac arrhythmia (ATSDR, 2000). Chronic exposure, even at lower levels, presents significant health risks such as neurological impairment, liver dysfunction, and carcinogenesis (EPA, 2011). Additionally, DCM is recognized as a potent skin irritant, exacerbating occupational hazards related to direct skin contact.
Occupational exposure has been particularly concerning, with most DCM-related fatalities in the United States from 1980 to 2018 occurring within workplace settings. Numerous non-fatal cases have also been documented, highlighting the importance of addressing long-term health consequences and prevention measures in workplaces (Hoang et al., 2021).
The carcinogenicity of DCM largely arises from its metabolic bioactivation pathway. Upon entering the body, DCM is metabolized primarily through the hepatic cytochrome P450 2E1 (CYP2E1) enzyme pathway and glutathione S-transferase theta 1 (GSTT1), generating reactive intermediates. The CYP2E1-mediated pathway results in the formation of carbon monoxide, while GSTT1-mediated metabolism leads to the production of formaldehyde (Figure 1). These reactive species can interact directly with cellular macromolecules, inducing DNA adduct formation, oxidative stress, and subsequent mutations. This genomic damage ultimately contributes to carcinogenesis observed in multiple tissues upon chronic exposure (Andersen et al., 2021).
Hazards of DCM Exposure:
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DCM is a skin irritant and can cause chemical burns, redness, and rashes.
Inhalation of DCM causes headaches, confusion, nausea, drowsiness, narcosis, suffocation, and carbon monoxide poisoning.
- DCM is a neurotoxin that can cause cerebral hypoxia and central nervous system depression.
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Figure 1:ÌýMetabolic transformations of DCM that are believed to lead to carcinogenic effects. (Figure has been redrawn, with style changes, from the paper:ÌýRegul. Toxicol. Pharmacol.Ìý2021, 120, 104858).
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What is Being Done to Reduce the Health Risks of DCM?
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Due to risk arising from DCM exposure, the EPA issued a (TSCA). The ruling affects anyone who manufactures, processes, distributes in commerce, uses, or disposes of DCM or products containing DCM.
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Can I Continue to Use DCM in the Laboratory?
The TSCA ruling identifies 13 conditional uses of DCM, one of which is use as a laboratory chemical. If you are using DCM in the laboratory, including academic laboratories, it is considered industry use, and requires a workplace chemical protection program (WCPP) be put into place.
The WCPP requires owners & operators of facilities using DCM to take appropriate measures to meet new inhalation limits (2 ppm as an 8-hour time weighted average), and develop and implement an exposure control plan.
Read More: Ìý(C&EN)
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New Inhalation Limit
- 2 ppm as an 8-hour time weighted average
- 2 ppm means that 2 out of every 1 million air molecules is DCM
EPA Compliance Deadlines forÌýDichloromethaneÌý
- April 2024: EPA Final Rule
EPA issues final rule prohibiting most uses of DCM.
- May 5, 2025: Initial Monitoring
Complete initial monitoring of inhalation exposures to DCM.
- August 1, 2025: Exposure Limits & PPE
EnsureÌýDCM exposures do not exceed EPA limits. Provide additional personal protective equipment if applicable.
- October 30, 2025: Exposure Control Plan
Develop, implement and document an exposure control plan.
- After October 2025: Periodic Montioring
Conduct regular monitoring every 3 months, 6 months, or 5 years, depending on initial monitoring results.Ìý
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With respect to personal protective gear (PPE), the use of nitrile gloves alone is no longer appropriate skin protection, and the use of respirators with cartridges alone is not considered appropriate control of exposure via inhalation. Follow university or company directives and guidelines for specific PPE requirements.
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If I Cannot Comply With the EPA Rules By the Deadline, How Can I Eliminate the Use of DCM in My Laboratory?
In light of the new regulation, labs must:
- Find an alternative to DCM that will serve the same function as DCM, keeping the original process design, or
- Design a new method or process that does not use DCM.
The Principles of Green ChemistryÌý& Green Engineering canÌýcan be used to develop a methodology for determining alternative solvents or processes for DCM without introducing a regrettable substitution.â€�
There are many alternate solvent options for DCM. However, one single solvent or solvent mixture cannot be recommended for replacing DCM since different use cases require different solvent properties and characteristics. A 3:1 mixture of ethyl acetate and ethanol, for example, can be an effective replacement for DCM in some column chromatography applications, but may not be an effective “catch-all� extraction solvent due to the differences, for example, in hydrogen bond basicity, acidity, and dipolarity characteristics that DCM, ethyl acetate and ethanol each possess when they interact with a given solute. See Synder’s solvent selectivity triangles (, J. Chromatogr. A, 1974, 92, 223. DOI:10.1016/S0021-9673(00)85732-5).
When considering a DCM replacement, it is important to carefully consider hazards and assess risks of the DCM substitute. In laboratories, experimental hazards can result from a variety of agents, conditions, and/or activities. The fact that a chemical may have an inherent hazard does not mean that it cannot be used in the laboratory as long as the hazard is recognized and risks are carefully minimized.
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How Do I Find an Alternative to DCM?
Solvent screening is a part of theÌýlarger process design cycle. TheÌýprocess can be continuallyÌýimproved and optimizedÌýthroughout experimental design.
1. DetermineÌýDCM’s Purpose
What role does DCM play in the reaction process?
DCM is commonly used as a:
- Reaction solventÌý
- Mobile phase in thin layer chromatography (TLC) and column chromatographyÌýÌý
- Cleaning solventÌý
- Extraction solventÌý
- Analysis chemical
2. Select Key Properties
Determine the key properties of the desired solvent based on its purpose. Some key properties for DCM include: polar, aprotic, low viscosity, low flammability, low boiling point, and immiscibiliity with water.Ìý
Physical parameters than can be assessed relating to these properties include: Hansen Solubility Parameter, boiling point, flash point, density, KOW,Ìýand viscosity.
3. Search Alternatives
Use a solvent guide, , and conduct literature search to determine possible alternatives with similar key properties and function to DCM.Ìý
The alternate solvent and reaction setup should meet the following criteria:
- Solvent must be inert under reaction conditionsÌý
- Chemistry must work
- Process must be safe and operable
- Waste must be able to be incinerated or treated
- Must be compliant with legislation
- Must not be cost prohibitive
4. Evaluate
Solvent screening is a part of the larger process design cycle. The process can be continually improved and optimized throughout experimental design and evaluation.
- Select solvents for screening
- Experimental evaluation
- Renew entire process or route to look for synergies
- Refine process design
How Do I Design a New Process to Avoid Using DCM?
A manufacturing route could be improved or changed to meet any or all of theÌýSELECTÌýcriteria:
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Safety –Removal/minimization of reactive hazards and toxicity and hazardous reagents/solvents.
Environmental � Removal/minimization of reagents/solvents harmful to the environment; volume and nature of waste.
Legal � No infringement of existing intellectual property.
Economics � Minimize cost of goods/meeting cost of goods target.
Control � Meeting quality specifications; process must be under control, validated, consistent impurity profile.
Throughput � Availability of raw materials; manufacturing time; maximized space time yield.
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Solvent Selection Tools, Guides & Resources
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The guide rates solvents against 5 categories: safety, health, environment (air), environment (water), and environment (waste). Key parameters and criteria were then chosen for each category. The summary table assigns a score from 1 to 10 for each solvent under the respective categories, with a score of 10 being of most concern and a score of 1 suggesting few issues.
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This tool allows you to interactively select solvents based upon the Principal Component Analysis (PCA) of the solvent’s physical properties. The tool includes 272 solvents based on 70 physical properties.
- : A learning page developed by the ACS Department of Lab Safety which provides the basics of lab safety and defines a risk management protocol.Ìý
- : Additional resources from the Green Chemistry Teaching and Learning Community (GCTLC)
Case Studies & Review Papers
- ÌýChem. Rev. 2021,â€�121, 1582â€�1622. DOI: 10.1021/acs.chemrev.0c00709Ìý
Extensive resource of information regarding the pros/cons of DCM and where greener solvents can be used in its place in select organic chemistry reactions and purification� processes.
- ÌýGreen Chem., 2022, 24, 3943â€�. DOI:10.1039/d2gc00698g​Ì�
An industry effort to reduce DCM use in synthesis and purification over a two-year period.
Webinars
- Ìý-ÌýBeyond Benign and ACS Laboratory Safety Institute Webinar
ACS Institute Online Courses
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Undergraduate students with general and some organic chemistry laboratory experience will apply RAMP principles to laboratory operations in this 17-hour course. Chemistry departments can also incorporate this course into their curriculum as a stand-alone course.Ìý
Secondary school educators or graduate students who manage chemical storerooms or teach with chemicals will find this course useful. Concepts of safe chemical management are highlighted using the RAMP risk management system in this 10-hour course.Ìý
Learn how to analyze your experiments and take incremental steps toward "greening" your protocols, while teaching your students how to evaluate the impact chemistry has on the world around them.Ìý
References
- International Agency for Research on Cancer (IARC).Ìý; IARC: Lyon, France, 2017; Volume 110, pp 177â€�254.
- Agency for Toxic Substances and Disease Registry (ATSDR).Ìý; U.S. Department of Health and Human Services: Atlanta, GA, USA, 2000.
- U.S. Environmental Protection Agency (EPA).Ìý; EPA/635/R-10/003F, Washington, DC, USA, 2011.Ìý
- Hoang, A.; Fagan, K.; Cannon, D.L.; Rayasam, S.D.; Harrison, R.; Shusterman, D. . JAMA Intern. Med. 2021, 181 (6), 797�805. DOI: 10.1001/jamainternmed.2021.1063.
- Dekant, W.; Jean, P.; Arts, J. . Regul. Toxicol. Pharmacol. 2021, 120, 104858. DOI: 10.1016/j.yrtph.2020.104858.
