Leachables from containers

Container size and physical design the concentration of materials leachable from glass decreases with increasing container size. The concentration of leached materials will increase with increasing surface-to-volume ratio for a given container size. In containers treated by the glass manufacturer, this extraction process can be significantly retarded [5]. 

Nasal Sprays Clarity, microbial bioburden, pH, particulate matter, unit spray medication content uniformity, droplet and/or particle size distribution, weight loss, pump delivery, microscopic evaluation of suspensions, particulate matter, extractables, leachables from plastic and elastomeric components of container closure and pump. 

Waste that is hazardous because it exhibits the toxicity characteristic also must be treated to remove this characteristic prior to disposal. Techniques to remove the toxicity characteristic include, for example, destruction of organic compounds by incineration or incorporation of the waste in an immobilizing waste form (e.g., grout). However, in contrast to ignitable, corrosive, or reactive waste, a properly treated toxic waste may still be considered hazardous in some cases, even if it is not characteristically hazardous after treatment and does not contain any listed substances. For example, a waste that is toxic because it contains high levels of heavy metals could be treated to reduce the leachability of the metals to acceptable levels by incorporation in an appropriate waste form, but the treated waste may still be considered hazardous when the toxic substances of concern are not destroyed by treatment and the possibility exists that their leachability from the waste form could increase substantially after disposal. 

Leachables in orally inhaled and nasal drug products (OINDP) are compounds which are present in the drug product due to leaching from container closure system components. Extractables are compounds that can be extracted from OINDP device components, or surfaces of the OINDP container closure system when in presence of an appropriate solvent(s) and/or condition(s). Leachables are often a subset of, or are derived directly or indirectly from, extractables. Extractables may, therefore, be considered as potential leachables in OINDPs. Some leachables may affect product quality and/or present potential safety risks, therefore regulatory guidance has provided some recommendations regarding the analysis and toxicological safety assessment (i.e., qualification) of such compounds. 

Metered-dose inhalations and nasal aerosols should be evaluated for appearance (including content, container, and the valve and its components), color, taste, assay, degradation products, assay for cosolvent (if applicable), dose content uniformity, labeled number of medication actuations per container meeting dose content uniformity, aerodynamic particle size distribution, microscopic evaluation, water content, leak rate, microbial limits, valve delivery (shot weight), and extractables and leachables from plastic and elastomeric components. Samples should be stored in upright and inverted/on-the-side orientations. 

Leachables in pharmaceutical products are trace amounts of chemicals originating from containers, medical devices or process equipment that end up as contaminants in medicinal products resulting in exposure to patients (Moffat, 2011). 

In 1999, researchers at the Florida State University [33] examined lead leachability from CRTs, and reported average lead concentrations of 18.5 mg/1 (above the 5.0 mg/1 regulatory hmit). Colored CRTs produced higher levels because the glass funnel in the CRT contains 24% lead, and the frit contains 70% lead. These two components exhibited the highest average lead concentration, 75.3 mg/1. Monochrome CRTs were found not to leach lead above the regulatory hmit. 

Sulfur Polymer Cement. SPC has been proven effective in reducing leach rates of reactive heavy metals to the extent that some wastes can be managed solely as low level waste (LLW). When SPC is combined with mercury and lead oxides (both toxic metals), it interacts chemically to form mercury sulfide, HgS, and lead sulfide, PbS, both of which are insoluble in water. A dried sulfur residue from petroleum refining that contained 600-ppm vanadium (a carcinogen) was chemically modified using dicyclopentadiene and oligomer of cyclopentadiene and used to make SC (58). This material was examined by the California Department of Health Services (Cal EPA) and the leachable level of vanadium had been reduced to 8.3 ppm, well below the soluble threshold limit concentration of 24 ppm (59). 

The CSIRO Division of Mineral Products, Port Melbourne, Victoria, Australia, is conducting research to develop a process to recover fluoride and aluminum from spent pot lining ash with concurrent production of an environmentally safe residue that is suitable for disposal. The proposed method involves initial calcination which thermally decomposes the cyanide in the spent pot lining. Successful completion of this research would reduce the amount of hazardous wastes that contain potentially harmful leachable cyanides that can enter the groundwater during open air storage. 

The acid extraction treatment system (AETS) reduces the concentrations and/or leachability of heavy metals in contaminated soils so that the soils can be returned to the original site. The main application of the AETS is to extract heavy metals from soils. Additional applications of the AETS include treatment of contaminated sediments, sludges, and other heavy-metal-containing solids. 

Tons of spent abrasives result each year from the removal of old paint from bridges. Because the spent abrasives contain metals from the paint, some spent abrasives may be considered hazardous by the Toxicity Characteristic (TC) criteria. Incorporation of the spent blasting abrasives in nonstructural concrete offers an opportunity to recycle the spent abrasives while immobilizing potentially leachable metals. Solvents that are less aggressive will mean that abrasives will be necessary in some applications. Study results indicated that considerable quantities of these spent abrasives can be solidified/stabilized while reducing the leachability of cadmium, chromium, and lead and producing compressive strengths over 6895 kN/m2 (1000 psi) (Brabrand and Loehr, 1993). 

The subject of extractables and leachables in drug products is an area of active discussion in the pharmaceutical industry. Further the regulatory agencies have issued guidances on this subject in recent years. The FDA guidance on container closure systems defines extractables and leachables as follows [124] Extractables are compounds that can be extracted from elastomeric or plastic components of the container closure system when in the presence of a solvent. Leachables are compounds that leach into the formulation from elastomeric or plastic components of... 

During development, evaluation of the consolidated materials was based primarily on two criteria, leachability and the concentration factor, i.e., the concentration of waste oxides on a volume basis. The concentration factor is directly affected by the residual porosity in a consolidated waste as well as by the dilution caused by the addition of consolidation aids. This factor can be as high as 1.2 g/cm3 for a fully dense ( 5 g/cm ) titanate waste prepared from the projected Barnwell plant solution composition. The factor is slightly lower for a titanate waste containing silicon and zeolite additions, which has a typical density of U.2 g/cm3. The leachability was determined by an "instantaneous leach test developed for fast, comparative evaluations of materials, the details of which are described elsewhere (l6). 

Samples of the red clay having uniform physical and chemical characteristics were provided by G. R. Heath of the University of Rhode Island. The samples were obtained from core LLUU-GPC-2, collected on October 11, 1976, at 30° 20.9 n, 157° 50.85 w, water depth 5821 meters, and are representative of the smectite-rich region of the red clays which occurs in the sediment at depths below about ten meters. In this region, the sediment appears to contain about five to six percent by weight leachable iron and manganese in the form of hydrous oxides. The remaining material appears to be dominated by iron-rich smectite and lesser, varying amounts of phillipsite (2). The results of a semi-quantitative (precision in data is within a factor of 2) elemental analysis... 

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