Residual Solvent Testing

What are residual solvents?
Hydrocarbon gases like butane and propane and organic solvents like ethanol, isopropanol and hexane are used to extract the essential oils out of cannabis to create highly concentrated, purified extracts. Residual Solvents are the solvents that remain in cannabis oils, shatters, waxes and budders after these extractions or after post-extraction processes such as winterization. Often the solvents used are not completely removed by purging with vacuum or heating, and so they can remain in the products that are smoked or inhaled by users in appreciable quantities. We test concentrates for residual solvents so that consumers have the best possible information available when choosing a finished extract.

The benefits of concentrates for users are obvious—high concentrations of cannabinoids can be delivered; a smaller amount of material is smoked for the amount of THC/CBD consumed, so that less toxins may be inhaled by users. The potent extracts can also be used to make edibles with high levels of cannabinoids for oral consumption. In some extracts, terpenes are also highly concentrated, invoking the full entourage effect, giving the maximal effect and superior taste.

What solvents are safe and at what levels?
Solvents commonly used for extraction include butane, propane, hexane, acetone and ethanol. The safety of many of these solvents has been studied. The US pharmacopeia has set guidelines as to what amount of a particular solvent a person can be exposed to on a daily basis without developing complications due to overexposure. The types of solvents are divided into three classes. Class 1 organics should never be used. Class 2 organics are not recommended for use outside of a Good Manufacturing Practice environment where these substances are tightly controlled and continuously monitored due to their dangerous effects. Class 3 are solvents that present no known human health hazard at levels normally accepted in pharmaceuticals. However, there are no long-term toxicity or carcinogenicity studies for many of the solvents in Class 3, and so safe levels for chronic use of these products have not been established.

Class 3 solvents commonly used for making extracts are Isopropanol, Ethanol, Acetone, Heptane, and Ethyl Ether and are regarded as presenting low toxic potential. Permitted daily exposure limits (PDEs) for these solvents have been published, and they have been shown to have low acute toxicity and no genotoxicity in studies on animals and in humans, and so are permitted at reasonable levels. Propane and Butane, two of the major solvents used for preparing extracts, are not on the Class 3 list but are regarded as safe.

The Washington State Liquor Control Board requires that solvent-based extracts using hydrocarbon gases that include n-Butane, Propane, Heptane and other solvents for use in inhalable extracts must be of at least 99% purity and that the products must undergo a residual solvent test. Under WAC Chapter 314-55-104, the parts per million for one gram of finished extract cannot exceed 500 ppm of residual solvent or gas when quality assurance tested per RCW 69.50.348, which is about 10 times lower than the limits set forth for Class 3 residual solvents by the FDA/International Conference on Harmonization. This recommendation is based on a 10 gram per day consumption level for a 50 kg person (50 mg/day). Extracts made from food grade ethanol, glycerin, propylene glycol, or CO2 of at least 99% purity do not require residual solvent testing.

Residual solvents are typically not acutely toxic but may have a long term effect on exposed individuals. An exposed person may exhibit eye, nose, and throat irritation, nausea, headaches, dizziness, fatigue, and allergic skin reaction. Propane and Butane are made by distillation of crude oil or refined natural gas, and are odorless, flammable hydrocarbon gases commonly used in lighter fluid, for fuel, for adhesives, cleaning solvents and degreasers. All of these products have been used for intoxication in their own right, and the effects of these include dizziness, euphoria, nausea, confusion and headaches and at higher levels can cause central nervous depression, respiratory and cardiac arrest. The key to using solvents safety in extracts is to use only very pure Class 3 solvents or highly purified propane and butane.

Butane
The MSDS for Power Butane 5x says it contains n-Butane, Isobutane, Propane, and other materials at no greater than 2% concentration (would need to be at least 99% hydrocarbon solvent under WA State law) but this varies from product to product. This agrees with our assessment of Mega Plus 5x lighter fluid which contains 4.8% Propane, 17.3% Isobutane, 76.5 % Butane, 1.3% Isopentane and 0.12% Pentane, along with another unidentified broad peak that represents roughly 1%. It is important to use hydrocarbon gases that come with an MSDS, which is required to list all components that comprise > 1% of the material and carcinogens that comprise > 0.1% of the material, since these are toxic at very low concentrations. 5x Butane and even 99.999% Butane contain significant amounts of the solvents Isopentane and Pentane and this unidentified solvent. After purging, the heavier Isopentane and Pentane remain in concentrates at higher concentrations than Propane and Butane because of their higher boiling points, and so are often present in larger quantities. These solvents are not particularly acutely toxic. This finding is of concern, however, because some preparations of Butane may contain small amounts of Benzene and 1,3-Butadiene, both of which are carcinogenic. How much of these materials may remain in concentrates after the lower boiling point materials are purged is currently under investigation in our lab using our new method. Our data also shows that with proper purging and product control residual solvents can be almost completely removed from concentrates.

What are unsafe solvents to use?
Naphtha and Hexane are other solvents used for extracting cannabinoids and are worthy of mention. Hexane is a petroleum distillate containing 6 carbon atoms, and is neurotoxic. Chronic exposure results in myelin sheath and axon degeneration. It has also been linked to Parkinson’s disease. Naphtha, found in kerosene, paint thinner, and used as a fuel, is also a petroleum distillate and contains heavier hydrocarbons such as n-Octane, n-Nonane, cycloalkanes, and branched alkanes of similar molecular weight. Naphtha and other byproducts found in the mixture are potentially cancer-causing. Because of these data, we do not recommend the use of these solvents for making concentrates.

What we offer
Analytical360 offers a validated testing method to determine the amount of residual solvents introduced during processing of concentrates. By monitoring the ppm levels of solvents we can will help identify raw materials and products that are free of harmful contamination. We are currently testing for residual solvents using GC-FID coupled with headspace sampling which is the technique recommended by USP 467 for residual solvents in pharmaceuticals. We have developed an in-house method that allows us to detect the light gases not included in USP 467. We are currently testing for propane, isobutane, n-butane, isopentane, n-pentane, isopropanol, ethanol, acetone, hexane and naphtha all in one assay.

The method currently utilized by Analytical 360 for testing residual solvents is the Gas Chromatography (GC) unit coupled with a headspace sampler and a Flame Ionization Detector (FID). Gas Chromatography is used in analytical chemistry for separating and measuring compounds that can be easily vaporized without decomposition. This test allows chemists to determine the purity of a particular substance, or identify and measure the individual components of a mixture. The process separates compounds on the basis of boiling point, or vapor pressure, similar to fractional distillation. An FID operates by detecting the ions formed from the combustion of the injected organic compounds with Hydrogen gas. The amount of detected ions is proportional to the concentration of each organic species in the mobile phase gas stream. As compounds elute off the column as determined based on their relative vapor pressures, their amounts are determined by the collection of ions by a high voltage detector. The current across the detector is directly proportional to the rate of ionization – which in turn depends upon the concentration of hydrocarbon in the sample. The ratio between the signal produced and the quantity is generally equal to number of carbon atoms for hydrocarbons. Oxygenates and other species that contain heteroatoms tend to have a lower response factor. Carbon monoxide and carbon dioxide are not detectable by FID.

Reference: AHPA Guidance on Residual Solvents in Extracts