Solvent choice is an important step in many research projects and encompasses many important factors. Properties such as polarity, solubility, and boiling point are often considered while health effects and environmental impacts are often overlooked.
When thinking about the overall safety and sustainable practices of the lab, health effects and environmental impacts must be considered as well rather than default to tradition or ease of access.
Table 1 provides a list of common solvents along with their associated hazards and the alternatives which help mitigate these hazards. The table is adapted from a study in 2008 conducted by Pfizer Global Research and Development as well as guidance from the University of Pennsylvania’s EH&S department, and Millipore Sigma.1,2,3 Solvents were compared based on worker safety, process safety, and environmental and regulatory concerns.
Table 1. Solvent Replacements
| Solvent | Flash Point (0C) | TLV* (ppm) | Issues | Replacement(s) |
|---|---|---|---|---|
| 1,2 dimethoxyethane | 0 | Data not determined | Carcinogen, toxic | tert-butyl methyl ether or 2-MeTHF |
| 1,2-Dichloroethane | 15 | 10 | Classified as a hazardous airborne pollutant, carcinogen | Dichloromethane |
| 1,4 Dioxane | 12 | 20** | Classified as a hazardous airborne pollutant, carcinogen, peroxide former | tert-butyl methyl ether or 2-MeTHF |
| Benzene | -11 | 0.5** | Carcinogen, reproductive toxicant low TLV, classified as a hazardous airborne pollutant | Toluene |
| Carbon tetrachloride | N/A | 5 | Carcinogen, toxic, depletes ozone, classified as a hazardous airborne pollutant | Dichloromethane |
| Chloroform | N/A | 10 | Classified as a hazardous airborne pollutant, carcinogen, reproductive toxicant | Dichloromethane |
| Dichloromethane (for chromatography) | N/A | 100 | Classified as a hazardous airborne pollutant, carcinogen | Ethyl acetate/heptane, ethyl acetate/alcohol |
| Dichloromethane (for extractions) | N/A | 100 | Classified as a hazardous airborne pollutant, carcinogen | Ethyl acetate, MTBE, Toluene, 2-MeTHF |
| Diethyl ether | -40 | 400 | Low flash point, peroxide former | tert-butyl methyl ether or 2-MeTHF |
| Di-isopropyl ether | -12 | 250 | Powerful peroxide former | tert-butyl methyl ether or 2-MeTHF |
| DMAC | 70 | 10** | Toxic | Acetonitrile |
| DMF | 57 | 10** | Classified as a hazardous airborne pollutant, toxic, carcinogen | Acetonitrile, Cyrene,γ- Valerolactone (GVL), Dimethyl isosorbide (DMI) |
| n-Hexane | -23 | 50 | Reproductive toxicant, more toxic than alternative | Heptane |
| NMP | 86 | Data not determined | Toxic | Acetonitrile, Cyrene,γ- Valerolactone (GVL), Dimethyl isosorbide (DMI) |
| Pentane | -49 | 1000 | Low flash point | Heptane |
| Pyridine | 20 | 1 | Carcinogen, reproductive toxicant, low TLV | Triethylamine (if pyridine is used as a base) |
| THF | -21.2 | 50 | Carcinogen, peroxide former | 2-MeTHF |
**Skin notation – indicates significant contribution to the overall exposure by cutaneous absorption
Beyond health hazards posed by solvents, it is also important to look at environmental impacts and overall sustainability. Labs interested in these “green” replacements can use biorenewable solvents which are sourced from renewable, sustainable biobased materials.3 Solvents such as acetone, 1-butanol, 2-propanol, and glycerol all have biorenewable options which do not produce harmful byproducts such as benzene, aldehydes, and ethers which are commonly found in petroleum manufacturing.3
Some of the solvent replacements found in Table 1 (e.g., replace hexane with heptane) are also considered green replacements having a less overall environmental impact.1,3 The replacement of DCM with an ethyl acetate/ethanol mixture is another great example of using greener alternatives to common solvents and opens the door to a larger conversation of greener chromatography techniques.3
Sigma has published a document titled “Greener Chromatography Solvents” which discusses how to achieve similar eluting strengths to DCM using an ethyl acetate/ethanol mixture. In its article “Greening Reverse-Phase Liquid Chromatography Methods Using Alternative Solvents for Pharmaceutical Analysis,” Yabre et al discuss multiple alternatives to the classic reverse phased solvents methanol and acetonitrile such as ethanol, acetone, and propylene carbonate and how these can be used without any major compromises to the chromatography.4
While this webpage is a good place to start looking for safer, greener alternatives, it is by no means comprehensive. Researchers are highly encouraged to investigate ways their experiments can be made safer and more sustainable, and to think critically about their solvent choice instead of just accepting what was done in the past.
References
- Alfonsi, K.; Colberg, J.; Dunn, P. J.; Fevig, T.; Jennings, S.; Johnson, T. A.; Kleine, H. P.; Knight, C.; Nagy, M. A.; Perry, D. A.; Stefaniak, M. Green chemistry tools to influence a medicinal chemistry and research chemistry based organization. Green Chem. 2008, 10, 31-36. DOI: 10.1039/B711717E.
- University of Pennsylvania Environmental Health and Radiation Safety. Fact Sheet: Solvent Alternatives. November 2018. https://ehrs.upenn.edu/health-safety/lab-safety/chemical-hygiene-plan/fact-sheets/fact-sheet-solvent-alternatives.
- Millipore Sigma. The Future of Solvents: BioRenewable. https://www.sigmaaldrich.com/US/en/campaigns/biorenewable-solvents.
- Moussa Yabré, Ludivine Ferey, Issa Touridomon Somé, Karen Gaudin. Greening Reversed-Phase Liquid Chromatography Methods Using Alternative Solvents for Pharmaceutical Analysis. Molecules 2018, 23(5), 1065. https://doi.org/10.3390/molecules23051065.