SOT ToxExpo

 

ToxExpo unites 350+ toxicology-related companies and organizations with 6,800+ attendees over three days. Exhibitors debut the latest products and services to executives and industry leaders.

Come Visit Toxikon at Booth #1151

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Toxikon's Poster Presentations at SOT ToxExpo

Toxicological Risk Assessment for Respiratory Medical Devices: Comparison of Methodology ISO10993 vs. ISO 18562

Speaker: Russell Sloboda
Location: CC Exhibit Hall
Date: Tuesday March 13, 2018
Time: 9:15am - 10:45am
Abstract Number/Poster Board number: 2167/P504

 

Respiratory medical devices come into contact with patients at a particularly vulnerable point and time. As a result, the exposure assessment for these devices is an important step in the evaluation of device safety and needs to be particularly concerned with potential releases of trace chemicals from the device materials, with special attention given to airborne releases of volatile organic compound (VOCs). ISO 10993 is the traditional standard for the evaluation of biocompatibility of medical devices and provides a framework for the safety evaluation. However, it does not sufficiently address the exposure through the air pathway. ISO 18562 , on the other hand, focuses on of exposure via inhalation, while also addressing leachables based on the accumulation of condensate in a breathing circuit. In some instances, however, ISO 10993 and ISO 18562 recommend a very different approach to the measurement of releasable chemicals and different assumptions for the risk assessment. A case study is presented for a toxicological risk assessment of chemicals released from a breathing cannula. A number of VOCs, SVOCs, NVOCs were identified in the E/L analysis, where the device was extracted in solutions of purified water, 50% EtOH, or hexane at 50°C for 72 hours. For example, cyclohexanone was detected at a level of 2540 μg/device in purified water (equivalent to 49.8 μg /mL) as per ISO 10993, which we interpret as a bounding estimate of daily exposure. In contrast, cyclohexanone was the only substance identified by the air pathway analysis as per ISO 18562, with a maximum level of 340 μg/m3, which yielded an exposure of 680 μg/day for an infant. As per ISO 18562, the total amount of liquid condensate that reaches the patient in a day is assumed to be 1 mL. Using this assumption, the cyclohexanone intake estimate is 730 μg/day, 49.8 μg/day from condensate based on total leachability plus 680 μg/day based on air pathway release, rather than 2540 μg/day. The dramatically different risk estimate derived using these regulatory guidelines points out the need to justify the use of one over the other. The distinctive features of air pathway devices and their unique nature of patient exposure will be discussed.


 

Risk Assessment of Leachable Substances from a Ventricular Catheter Using Data Extractions from Exhaustive

Speaker: Kevin Connor
Location: CC Exhibit Hall 
Date: March 14, 2018
Time: 3:00pm - 4:30pm
Abstract Number/Poster Board number: 2886/P411

 

As part of a toxicological risk assessment, an analysis of leachable substances was conducted for a ventricular catheter, which is intended for use in patients to drain CNS fluid that contributes to excess intracranial fluid pressure. To capture leachables that may be released during long term implantation, a chemical characterization was performed using prolonged extractions, along with non-volatile residue (NVR) as a surrogate to monitor the endpoint of exhaustive release of organic chemicals. Separate extractions were conducted with solvents of three different polarities. Isopropanol and hexane, which exhibit somewhat nonpolar characteristics, yielded much higher extractable masses of organic analytes - chiefly siloxanes - than purified water. Based on the results of NVR analysis, concentrations of individual chemical analytes were measured following a single, prolonged solvent extraction of the device. With isopropanol, successive extractions demonstrated exhaustive conditions were achieved (based on NVR levels <10% of the initial extracted amount) after three 72-hour extractions at 50 degrees C, with solvent removal and analysis of NVR after each step. The NVR data exhibited an asymptotic depletion curve consistent with previous GC/MS analysis results from consecutive extractions. To evaluate whether the prolonged, continuous extraction was exhaustive, the leachable NVR from 3 consecutive 72-hour extractions was compared to NVR measured from a single, prolonged extraction covering the same time frame (216 hrs). A statistical comparison found that leachable NVR was significantly higher with three successive extractions as compared to that observed following a single prolonged extraction, and suggests that solvent replenishment with successive extractions is necessary to overcome the influence of the polymer/liquid partition coefficient. These results will be discussed in the context of the physical-chemical properties that can limit leachability, e.g., analyte solubility, polymer swelling, diffusion rate, and equilibrium partitioning. Based on these findings, the total leachable analyte mass as determined with a single, prolonged extraction was adjusted by a factor of 1.24, equal to leachable NVR measured with multiple, successive extractions divided by that measured with a single, prolonged extraction. Use of this adjustment assured that leachability was not underestimated when evaluating risks based on prolonged extraction data.  ;

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