| <!DOCTYPE html> |
| <html lang="en"> |
| <head> |
| <meta charset="UTF-8"> |
| <title>CHRIS Report</title> |
|
|
| |
| |
| <script id="MathJax-script" async src="{{ url_for('static',filename='mathjax/tex-mml-svg.js') }}"></script> |
| <link rel= "stylesheet" type= "text/css" href= "{{ url_for('static',filename='styles.css') }}"> |
|
|
| <style> |
| * { |
| box-sizing: border-box; |
| } |
| |
| |
| .column { |
| float: left; |
| width: 50%; |
| padding: 10px; |
| vertical-align: top; |
| align: center; |
| } |
| |
| |
| .row:after { |
| content: ""; |
| display: table; |
| clear: both; |
| } |
| </style> |
|
|
| </head> |
|
|
| <img src="{{ url_for('static',filename='images/FDAlogo.png') }}" style="float: left;" height="100"/> |
| <img src="{{ url_for('static',filename='images/FDAgraphic.png') }}" style="float: right;" height="100"/> |
| <br clear="all" /> |
|
|
| <header> |
| <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculators (CHRIS) Report - Bulk chemicals </h1> |
| </header> |
|
|
| <body> |
|
|
| <p> The following report was generated using CHRIS-Bulk Chemicals (RST) v.1.0 on |
| <script> document.write(new Date().toLocaleDateString()); </script>. |
| </p> |
|
|
| <h2> Compound </h2> |
|
|
| <div class="container"> |
| <div class="row"> |
| <div class="column"> |
| Input :: {{chemName}} <br> <br> |
| IUPAC Name :: {{iupac}} <br> <br> |
| CAS :: {{cas}} <br> <br> |
| Molecular weight (g/mol) :: {{'%0.4f'%MW|float}} |
| {% if ceramic %} :: ceramic detected, assume maximum Mw {% endif %} |
| <br> <br> |
| {% if show_properties %} |
| LogKow :: {{LogP}}{{LogP_origin}}<br> <br> |
| Density (g/cm<sup>3</sup>) :: {{rho}}{{rho_origin}}<br> <br> |
| Melting point (°C) :: {{mp}}{{mp_origin}}<br> <br> |
| {% endif %} |
| SMILES :: {{smiles}} |
| </div> |
| <div class="column"> |
| <img src="{{molImage}}"/> |
| </div> |
| </div> |
| </div> |
|
|
|
|
| <h2> Exposure </h2> |
|
|
| <p> |
| <u> Diffusion calculation for leaching from {{polymers[pIndex]}} estimates the worst case single day exposure = {{release}} mg. </u> |
| <p> |
|
|
| <p> |
| This estimate was derived using solutions to the conservative plane sheet model for mass release, \( M \): |
|
|
| \[ |
| M(\tau)= \left\{ |
| \begin{array}{cr} |
| 2 M_0 \sqrt{\tau/\pi} & \tau \leq 0.2 \\ |
| M_0\left(1-8 \exp\left[-\tau \pi^2/4 \right]/\pi^2\right) & \tau > 0.2 |
| \end{array} \right. |
| \] |
|
|
| where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and volume of the polymer matrix, respectively, \( M_0 \) is total mass initially contained in the polymer, \( D \) is a conservative estimate of the diffusion coefficient of the leachable within the polymer matrix, and \( t \) is time. Based on the input provided, the calculation was based on the following values: |
| </p> |
|
|
| <p> |
| \( A \) = {{area}} cm<sup>2</sup> <br> |
| \( V \) = {{vol}} cm<sup>3</sup> <br> |
| \( M_0 \) = {{amount}} mg <br> |
| \( D \) = {{diff}} cm<sup>2</sup>/s <br> |
| \( t \) = {{time}} h <br> |
| </p> |
|
|
| <p> |
| In addition to the maximum daily (day 1) release rate, it can be helpful to examine the decay in release rate over time predicted by the model, |
| which is illustrated for the first 30 days of exposure in the plot below: |
| </p> |
|
|
| <img src="{{ image }}"/> |
|
|
| <h2> Assumptions </h2> |
|
|
| {% if assume[0] and assume[1] and assume[2] and assume[3] and assume[4] %} |
|
|
| <p> |
| <font color="green"> You have confirmed your system complies with the model assumptions and no further data are needed to support using the exposure estimation provided by CHRIS in a submission to CDRH. </font> |
| </p> |
|
|
| {% else %} |
|
|
| <p> |
| <font color="red"> You have not confirmed compliance with one or more of the underlying assumptions upon which the exposure calculation is based. Therefore, it may be necessary to provide a justification and supporting data for why the results obtained for a system that may not comply with unchecked assumptions below are still valid if the assessment is used to support a submission to CDRH: </font> <br> |
| </p> |
|
|
| {% if not assume[0] %} |
| <font color="red"> • The polymer matrix does not swell or degrade in the clinical use environment. <br> </font> |
| {% endif %} |
|
|
| {% if not assume[1] %} |
| <font color="red"> • Any particles/aggregates of the chemical are much smaller than the smallest component dimension (≤ 50x). <br> </font> |
| {% endif %} |
|
|
| {% if not assume[2] %} |
| <font color="red"> • The chemical is homogeneously distributed throughout the polymer. <br> </font> |
| {% endif %} |
|
|
| {% if not assume[3] %} |
| <font color="red"> • The total amount of the chemical is present in dilute concentrations (≤ 2 %). <br> </font> |
| {% endif %} |
|
|
| {% if not assume[4] %} |
| <font color="red"> • Manufacturing processes do not impact the integrity of the polymer. <br> </font> |
| {% endif %} |
|
|
| {% endif %} |
|
|
| <h2> Screening level toxicological risk assessment </h2> |
|
|
| <p> |
| The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}} mg. Based on the exposure estimation this results in a margin of safety (MOS) of {{MOS}}. |
| </p> |
|
|
| {% if MOS >= 1 %} |
|
|
| <p> |
| <font color="green"> The MOS based on the mutagenic TTC is greater than one; therefore, no further analysis is needed for systemic biocompatibility endpoints. </font> |
| </p> |
|
|
| <p> |
| <font color="red"> *Note*: This assessment assumes that the chemical is not in the cohort of concern. </font> |
| </p> |
|
|
| {% else %} |
|
|
| <p> |
| <font color="red"> The MOS based on the mutagenic TTC is less than one; therefore, further analysis is needed to address systemic biocompatibility endpoints. For example, a compound-specific tolerable intake value could be independently derived and compared to the exposure estimate provided above. </font> |
| </p> |
|
|
| {% endif %} |
|
|
| <button type="button" onclick="javascript:history.back()">Back</button> |
|
|
| </body> |
| </html> |
|
|
