Merge branch 'development' into smiles

color_module/static/COU.html

@@ -1,9 +1,17 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-COU</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+    
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 <h2 id="context-of-use-cou">Context of Use (COU)</h2>
 <p>The Color Hazard and RISk calculator (CHRIS) is (proposed to be) qualified to conduct screening level risk assessments to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)<a href="#fn1" class="footnote-ref" id="fnref1" role="doc-noteref"><sup>1</sup></a>. These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or other additives and impurities associated with CAs in a device would require additional justification and/or testing to demonstrate acceptable biological risk. The output of CHRIS is a conservative margin of safety (MOS = toxicological safety limit ÷ exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric medical device component. Based on the MOS value, the calculator determines if further assessment of one or more biocompatibility endpoints is necessary for the CA and/or associated impurities.</p>
@@ -32,7 +40,7 @@
 <li>The polymer does not swell or degrade in-vivo, nor does the presence of CA impact the integrity of the polymer.</li>
 <li>The total amount of CA is present in dilute concentrations (&lt;= 2 % m/v) within the colored component.</li>
 <li>The CA is homogeneously distributed throughout the polymer.</li>
-<li>The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (&gt;= 50x).</li>
+<li>The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (&lt;= 50x).</li>
 </ol>
 <p>While these assumptions are typically valid for color additive containing device components, users of CHRIS must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system. Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA. These polymers are listed below. To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified. For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature. For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water. Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol. Therefore, for substances with a molecular weight &gt; 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight &lt; 100 g/mol, CHRIS currently cannot be used to estimate exposure.</p>
 <ul>

color_module/static/COU.md

@@ -1,16 +1,30 @@
 ```{=html}
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-COU</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+    
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 ```
 
 ## Context of Use (COU)
 
-The Color Hazard and RISk calculator (CHRIS) is (proposed to be) qualified to conduct screening level risk assessments to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)[^1].  These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or other additives and impurities associated with CAs in a device would require additional justification and/or testing to demonstrate acceptable biological risk.  The output of CHRIS is a conservative margin of safety (MOS = toxicological safety limit ÷ exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric medical device component.  Based on the MOS value, the calculator determines if further assessment of one or more biocompatibility endpoints is necessary for the CA and/or associated impurities.
+The Color Hazard and RISk calculator (CHRIS) is (proposed to be) qualified to conduct screening level risk assessments 
+to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)[^1]. These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or 
+other additives and impurities associated with CAs in a device would require additional justification and/or testing to 
+demonstrate acceptable biological risk.  The output of CHRIS is a conservative margin of safety (MOS = toxicological 
+safety limit &#247; exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric 
+medical device component.  Based on the MOS value, the calculator determines if further assessment of one or more 
+biocompatibility endpoints is necessary for the CA and/or associated impurities.
 
 Because CHRIS only addresses CAs, a favorable outcome by CHRIS does not imply acceptable biological risk for the final finished form of a medical device.  CHRIS is also not intended to establish device classification or identify biocompatibility requirements.  However, in addition to providing guidance to device manufacturers on acceptable levels of CA in a particular device, CHRIS can potentially be used to:
 
@@ -37,7 +51,7 @@ CHRIS provides clinically relevant, yet still conservative, exposure dose estima
 1. The polymer does not swell or degrade in-vivo, nor does the presence of CA impact the integrity of the polymer.
 1. The total amount of CA is present in dilute concentrations (<= 2 % m/v) within the colored component.
 1. The CA is homogeneously distributed throughout the polymer.
-1. The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (>= 50x).
+1. The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (<= 50x).
 
 While these assumptions are typically valid for color additive containing device components, users of CHRIS must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system.  Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA.  These polymers are listed below.  To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified.  For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature.  For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water.  Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol.  Therefore, for substances with a molecular weight > 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight < 100 g/mol, CHRIS currently cannot be used to estimate exposure.
 

color_module/static/FAQ.html

@@ -1,9 +1,16 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-FAQ</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 <h2 id="frequently-asked-questions">Frequently asked questions</h2>
 <h3 id="what-is-the-primary-purpose-of-chris">What is the primary purpose of CHRIS?</h3>
@@ -23,10 +30,10 @@
 <p>For any impurities present, CHRIS compares the total amount of impurities to the appropriate TTC value. The user should also review and confirm compliance with the relevant Code of Federal Regulations (CFR) listings as part of the submission package, i.e. in addition to any output of CHRIS. Examples of CFR listings for color additives specifically addressed by CHRIS are given below:</p>
 <ul>
 <li>Titanium dioxide (CAS#:13463-67-7) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-D/section-73.3126">21 CFR 73.3126</a> (medical devices); <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-A/section-73.575">21 CFR 73.575</a> (foods)</li>
-<li>Carbon black (CAS#:1333-86-4) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3054">21 CFR 178.3297</a> (indirect food substances); <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297">21 CFR 21 CFR 74.3054</a> (medical devices)</li>
+<li>Carbon black (CAS#:1333-86-4) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297">21 CFR 178.3297</a> (indirect food substances); <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3054">21 CFR 21 CFR 74.3054</a> (medical devices)</li>
 <li>Pigment brown 24 (CAS#:68186-90-3) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297">21 CFR 178.3297</a> (indirect food substances)</li>
 <li>Zinc Oxide (CAS#:1314-13-2) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-B/section-73.1991">21 CFR 73.1991</a> (drugs); <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-C/section-73.2991">21 CFR 73.2991</a> (cosmetics)</li>
-<li>Pigment Red 101 (CAS#: 1309-37-1) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297">21 CFR 186.1374</a> (indirect food substances)</li>
+<li>Pigment Red 101 (CAS#: 1309-37-1) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-186/subpart-B/section-186.1374">21 CFR 186.1374</a> (indirect food substances)</li>
 <li>Pigment blue 15 (CAS#:147-14-8) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3045">21 CFR 74.3045</a> (medical devices)</li>
 <li>Phthalocyanine green (CAS#:1326-53-6) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-D/section-73.3124">21 CFR 73.3124</a> (medical devices)</li>
 <li>Pigment Yellow 138 (CAS#:30125-47-4) - <a href="https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297">21 CFR 178.3297</a> (indirect food substances)</li>

color_module/static/FAQ.md

@@ -1,10 +1,17 @@
 ```{=html}
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-FAQ</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 ```
 
@@ -42,10 +49,10 @@ Provisional tolerable intake values (TIs) were derived for color additives commo
 For any impurities present, CHRIS compares the total amount of impurities to the appropriate TTC value. The user should also review and confirm compliance with the relevant Code of Federal Regulations (CFR) listings as part of the submission package, i.e. in addition to any output of CHRIS. Examples of CFR listings for color additives specifically addressed by CHRIS are given below:
 
 * Titanium dioxide (CAS#:13463-67-7) - [21 CFR 73.3126](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-D/section-73.3126) (medical devices); [21 CFR 73.575](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-A/section-73.575) (foods)
-* Carbon black (CAS#:1333-86-4) - [21 CFR 178.3297](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3054) (indirect food substances); [21 CFR 21 CFR 74.3054](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297) (medical devices)
+* Carbon black (CAS#:1333-86-4) - [21 CFR 178.3297](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297) (indirect food substances); [21 CFR 21 CFR 74.3054](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3054) (medical devices)
 * Pigment brown 24 (CAS#:68186-90-3) - [21 CFR 178.3297](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297) (indirect food substances)
 * Zinc Oxide (CAS#:1314-13-2) - [21 CFR 73.1991](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-B/section-73.1991) (drugs); [21 CFR 73.2991](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-C/section-73.2991) (cosmetics)
-* Pigment Red 101 (CAS#: 1309-37-1) - [21 CFR 186.1374](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297) (indirect food substances)
+* Pigment Red 101 (CAS#: 1309-37-1) - [21 CFR 186.1374](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-186/subpart-B/section-186.1374) (indirect food substances)
 * Pigment blue 15 (CAS#:147-14-8) - [21 CFR 74.3045](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-74/subpart-D/section-74.3045) (medical devices)
 * Phthalocyanine green (CAS#:1326-53-6) - [21 CFR 73.3124](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73/subpart-D/section-73.3124) (medical devices)
 * Pigment Yellow 138 (CAS#:30125-47-4) - [21 CFR 178.3297](https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-178/subpart-D/section-178.3297) (indirect food substances)

color_module/static/README.html

@@ -1,9 +1,16 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-README</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 <h2 id="overview">Overview</h2>
 <p>The Color Hazard and RISk calculator (CHRIS) is a tool under development within the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). The tool enables the user to perform rapid, screening level toxicological risk assessments of color additives and additives and impurities associated with the color additive that might be released from a polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a tolerable exposure (TE) or threshold of toxicological concern (TTC) value. The tool assists the user in determining (a) whether the toxicological risk of a color additive associated substance should be further assessed and/or (b) the potential impact of the substance on device biocompatibility.</p>
@@ -14,7 +21,7 @@
 <li><p>If a color additive associated substance is present in multiple polymer medical device components, CHRIS will not screen the potential risk of the substance from all the polymer components that contain it. CHRIS exposure estimates from each component may be manually summated to estimate total exposure to each substance and manually compared to the TE or TTC for that substance.</p></li>
 <li><p>If the substance levels present in the device are unknown, the calculator currently cannot be used to screen the risk associated with the respective compound(s).</p></li>
 <li><p>CHRIS cannot be used to screen the potential risk of polymer medical device components that contact the body by the inhalation route.</p></li>
-<li><p>The exposure model employed by CHRIS assumes a plane sheet geometry as worst-case. This assumption should be valid for most medical device components; however, potential exceptions exist. Specifically, this assumption can underestimate exposure when the geometry of the exposed surface area is concave, e.g. body contact is limited to the lumen of a catheter. When the exposed surface area is concave, underestimating exposure can be mitigated by assuming the patient will be exposed to all surfaces of the component, i.e. exposed surface area = total component surface area.</p></li>
+<li><p>The exposure model employed by CHRIS assumes a plane sheet geometry as worst-case. This assumption should be valid for most medical device components; however, potential exceptions exist. Specifically, this assumption can underestimate exposure when the geometry of the exposed surface area is concave, e.g., body contact is limited to the lumen of a catheter. When the exposed surface area is concave, underestimating exposure can be mitigated by assuming the patient will be exposed to all surfaces of the component, i.e., exposed surface area = total component surface area.</p></li>
 </ol>
 <h2 id="assumptions">Assumptions</h2>
 <p>In addition to plane sheet geometry, four additional assumptions were made in the derivation of the exposure model, which include:</p>
@@ -33,9 +40,9 @@
 <p><em>Amount</em> - Enter the total mass of the substance in the component being evaluated expressed in milligrams.</p>
 <p><em>Total impurity concentration</em> - If you have selected a color additive, please enter the combined concentration of all impurities associated with the color additive as a percentage (% mass/mass).</p>
 <h3 id="polymer-matrix">Polymer matrix</h3>
-<p><em>Matrix</em> - Please select your polymer matrix from the list. If your polymer is not listed below, please select “Other polymer”. For polymer mixtures/blends, co-polymers, or composites (e.g. glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e. the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.</p>
+<p><em>Matrix</em> - Please select your polymer matrix from the list. If your polymer is not listed below, please select “Other polymer”. For polymer mixtures/blends, co-polymers, or composites (e.g., glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e., the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.</p>
 <p><em>Mass</em> - Enter the mass of the polymer matrix in grams.</p>
-<p><em>Density</em> - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g. +/- 10%) is acceptable.</p>
+<p><em>Density</em> - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g., +/- 10%) is acceptable.</p>
 <h3 id="device-characteristics">Device characteristics</h3>
 <p><em>Exposed surface area</em> - Enter the patient contacting surface area of the color additive containing component being evaluated in square centimeters. This includes both direct and indirect patient contact.</p>
 <p><em>Exposure type</em> - Select the appropriate exposure category: &gt; 30 days = long-term, &gt; 24 hours - 30 days = prolonged, ≤ 24 hours = limited. For limited exposures (≤ 24 hours), please enter the maximum exposure time in hours.</p>
@@ -44,7 +51,7 @@
 <p><em>Biostability of the matrix</em> - While many of the matrices listed within CHRIS will not appreciably swell or degrade in any physiological environment, this can not be generalized. For example, silicones may swell in lipid-rich environments. Chemical compatibility of the polymer matrix with the use environment can be assessed based on historical use and/or evaluation of swelling and/or degradation propensity in physiologically relevant media.</p>
 <p><em>Particle/aggregate size and distribution</em> - CHRIS relies on the color additive having a distribution that is macroscopically homogeneous within the matrix (e.g. CAs used for surface marking would be excluded); thus, any particles or aggregates must be small relative to the component and homogeneously distributed. This can be confirmed/justified through the use of particle coatings and/or dispersants in the concentrate to prevent aggregation and promote homogeneity, macroscopic observations of color uniformity, and/or microscopic observations to evaluate the potential for surface segregation phenomena, such as blooming.</p>
 <p><em>Dilute concentration</em> - The model relies on a concentration independent diffusion coefficient, which assumes any color additives are present only in dilute quantities. Confirming that the total amount of color additives present is ≤ 2 m/v % is sufficient to conform with this assumption. It may be possible to justify that the CHRIS calculation for a dilute compound will remain protective if the total concentration is in excess of 2 m/v %, if the presence of additional compound could reasonably be expected to inhibit rather than promote diffusion, e.g. second phase particulates.</p>
-<p><em>Matrix stability</em> - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g. during sterilization) or other physicochemical changes (e.g. excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.</p>
+<p><em>Matrix stability</em> - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g., during sterilization) or other physicochemical changes (e.g., excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.</p>
 <h3 id="exposure-assessment">Exposure Assessment</h3>
 <p>Once the fields described have been populated for the polymeric component being evaluated, click the <strong>Estimate exposure</strong> button. The risk assessment output includes the following information:</p>
 <ol type="1">

color_module/static/README.md

@@ -1,10 +1,17 @@
 ```{=html}
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <title>CHRIS-README</title>
+    <link rel="stylesheet" href="styles.css">
+    <meta charset="UTF-8">
+</head>
 
 <header>
     <img src="images/FDAlogo.png" style="float: left;" height="100"/>
     <img src="images/FDAgraphic.png" style="float: right;"  height="100"/>
     <br clear="all" />
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS)- color additives</h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 ```
 
@@ -24,7 +31,7 @@ The Color Hazard and RISk calculator (CHRIS) is a tool under development within
 
 (4) CHRIS cannot be used to screen the potential risk of polymer medical device components that contact the body by the inhalation route.
 
-(5) The exposure model employed by CHRIS assumes a plane sheet geometry as worst-case. This assumption should be valid for most medical device components; however, potential exceptions exist. Specifically, this assumption can underestimate exposure when the geometry of the exposed surface area is concave, e.g. body contact is limited to the lumen of a catheter. When the exposed surface area is concave, underestimating exposure can be mitigated by assuming the patient will be exposed to all surfaces of the component, i.e. exposed surface area = total component surface area.
+(5) The exposure model employed by CHRIS assumes a plane sheet geometry as worst-case. This assumption should be valid for most medical device components; however, potential exceptions exist. Specifically, this assumption can underestimate exposure when the geometry of the exposed surface area is concave, e.g., body contact is limited to the lumen of a catheter. When the exposed surface area is concave, underestimating exposure can be mitigated by assuming the patient will be exposed to all surfaces of the component, i.e., exposed surface area = total component surface area.
 
 ## Assumptions
 
@@ -53,17 +60,17 @@ The user inputs the following information into CHRIS: (a) the identity, molecula
 
 ### Polymer matrix
 
-*Matrix* - Please select your polymer matrix from the list. If your polymer is not listed below, please select "Other polymer". For polymer mixtures/blends, co-polymers, or composites (e.g. glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e. the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.
+*Matrix* - Please select your polymer matrix from the list. If your polymer is not listed below, please select "Other polymer". For polymer mixtures/blends, co-polymers, or composites (e.g., glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e., the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.
 
 *Mass* - Enter the mass of the polymer matrix in grams.
 
-*Density* - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g. +/- 10%) is acceptable.
+*Density* - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g., +/- 10%) is acceptable.
 
 ### Device characteristics
 
 *Exposed surface area* - Enter the patient contacting surface area of the color additive containing component being evaluated in square centimeters. This includes both direct and indirect patient contact.
 
-*Exposure type* - Select the appropriate exposure category: > 30 days = long-term, > 24 hours - 30 days = prolonged, ≤ 24 hours = limited. For limited exposures (≤ 24 hours), please enter the maximum exposure time in hours.
+*Exposure type* - Select the appropriate exposure category: > 30 days = long-term, > 24 hours - 30 days = prolonged, &#8804; 24 hours = limited. For limited exposures (&#8804; 24 hours), please enter the maximum exposure time in hours.
 
 ### Conformance to Assumptions
 
@@ -75,7 +82,7 @@ The exposure model relies on assumptions that are typically valid for bulk solut
 
 *Dilute concentration* - The model relies on a concentration independent diffusion coefficient, which assumes any color additives are present only in dilute quantities. Confirming that the total amount of color additives present is ≤ 2 m/v % is sufficient to conform with this assumption. It may be possible to justify that the CHRIS calculation for a dilute compound will remain protective if the total concentration is in excess of 2 m/v %, if the presence of additional compound could reasonably be expected to inhibit rather than promote diffusion, e.g. second phase particulates.
 
-*Matrix stability* - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g. during sterilization) or other physicochemical changes (e.g. excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.
+*Matrix stability* - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g., during sterilization) or other physicochemical changes (e.g., excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.
 
 ### Exposure Assessment
 

color_module/templates/index.html

@@ -3,10 +3,10 @@
 <head>
     <meta charset="UTF-8">
     <title>CHRIS</title>
-
   <script src="https://cdn.jsdelivr.net/npm/jquery@3.5.1/dist/jquery.slim.min.js" integrity="sha384-DfXdz2htPH0lsSSs5nCTpuj/zy4C+OGpamoFVy38MVBnE+IbbVYUew+OrCXaRkfj" crossorigin="anonymous"></script>
   <script src="https://cdn.jsdelivr.net/npm/popper.js@1.16.1/dist/umd/popper.min.js" integrity="sha384-9/reFTGAW83EW2RDu2S0VKaIzap3H66lZH81PoYlFhbGU+6BZp6G7niu735Sk7lN" crossorigin="anonymous"></script>
   <script src="https://cdn.jsdelivr.net/npm/bootstrap@4.6.1/dist/js/bootstrap.min.js" integrity="sha384-VHvPCCyXqtD5DqJeNxl2dtTyhF78xXNXdkwX1CZeRusQfRKp+tA7hAShOK/B/fQ2" crossorigin="anonymous"></script>
+
   <link rel= "stylesheet" type= "text/css" href= "{{ url_for('static',filename='styles.css') }}">
 
 </head>
@@ -16,20 +16,13 @@
 <br clear="all" />
 
 <header>
-  <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
+  <h1 style="text-align:center">CHRIS: FDA's <font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator</h1>
 </header>
 
-<p><strong>Disclaimer: This module only addresses risk associated with the presence of color additives and additives and impurities
-  associated with the color additive. Therefore, a favorable outcome does not imply acceptable biological risk for the final
-  finished form of a medical device. Further, a successful evaluation does not address local biocompatibility endpoints, and
-  therefore additional testing may be needed despite a positive outcome from CHRIS.  Because there may be additional restrictions
-  based on specific device guidance and code of federal regulation (CFR) listings, users should also review the relevant documents
-  for their device type and color additive. </strong></p>
+<p><strong>Disclaimer: CHRIS only addresses risk associated with the presence of color additives and additives and impurities associated with the color additive. Therefore, a favorable outcome by CHRIS does not imply acceptable biological risk for the final finished form of a medical device. Further, a successful CHRIS evaluation does not address local biocompatibility endpoints, and therefore additional testing may be needed despite a positive outcome from CHRIS.  Because there may be additional restrictions based on specific device guidance and code of federal regulation (CFR) listings, users should also review the relevant documents for their device type and color additive. </strong></p>
 
 
-<p> For details on how to use CHRIS, please read the <a href="{{url_for('.static', filename='README.html')}}"> instructions.</a> and
-  <a href="{{url_for('.static', filename='COU.html')}}"> context of use (COU)</a>. Answers to frequently asked questions can be
-  found <a href="{{url_for('.static', filename='FAQ.html')}}"> here</a>.</p>
+<p> For details on how to use CHRIS, please read the <a href="{{url_for('static', filename='README.html')}}"> instructions.</a> and <a href="{{url_for('static', filename='COU.html')}}"> context of use (COU)</a>. Answers to frequently asked questions can be found <a href="{{url_for('static', filename='FAQ.html')}}"> here</a>.</p>
 
 <body>
 
@@ -45,15 +38,15 @@ Identity: <select name="CA" id="CA" onchange="javascript:caCheck();">
     <option value="{{CA}}">{{CA}}</option>
   {% endfor %}
 </select> 
-<span id="otherID" style="visibility:hidden">
-    &nbsp; &rArr; Chemical name: <input name="chemName" id="chemName" type="text" value="ENTER CHEMICAL NAME" required><br>
-  </span>
+<span id="otherID" style="display:none">
+    &nbsp; &rArr; Chemical name: <input name="chemName" id="chemName" type="text" value="ENTER CHEMICAL NAME" required>
+  </span> <br>
 
-Molecular weight (g/mol): <input name="MW" id="MW" step="any" value="1100" min="100.0" max="1100.0" type="number" disabled><br>
+Molecular weight (g/mol): <input name="MW" id="MW" step="any" value="1100" min="100.0" max="1100.0" type="number" disabled required><br>
 
-Amount (mg): <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number"> <br>
+Amount (mg): <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number" required> <br>
 
-Total impurity concentration (%): <input name="impurity" id="impurity" value="0.1" step="any" min="0.000001" max='100.0' type="number"> <br>
+Total impurity concentration (%): <input name="impurity" id="impurity" value="0.1" step="any" min="0.000001" max='100.0' type="number" required> <br>
 
 <!-- Javascript to reveal/hide CA selection box -->
 
@@ -74,12 +67,14 @@ function caCheck() {
         document.getElementById('MW').disabled = false;
     } 
     if (iCA >= 11) {
-      document.getElementById('otherID').style.visibility = 'visible';
+      document.getElementById('otherID').style.display = "inline";
       document.getElementById('chemName').value = "ENTER CHEMICAL NAME";
     } else {
-      document.getElementById('otherID').style.visibility = 'hidden';
+      document.getElementById('otherID').style.display = "none";
     }
 }
+
+$(window).on('pageshow', function() { caCheck(); });
 </script>
 
 <!-- Modal -->
@@ -114,8 +109,8 @@ Matrix: <select name="polymer">
     <option value="{{polymer}}">{{polymer}}</option>
   {% endfor %}
 </select> <br>
-Mass (g): <input name="mass" id="mass" step="any" value="1.0" min="0.000001" type="number"> <br>
-Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value="1.0" min="0.01" type="number">
+Mass (g): <input name="mass" id="mass" step="any" value="1.0" min="0.000001" type="number" required> <br>
+Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value="1.0" min="0.01" type="number" required>
 
 <!-- Modal -->
 <div id="PolymerModal" class="modal fade" role="dialog">
@@ -144,13 +139,13 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
 
   <h3> Device characteristics <button type=button class="Info_btn" data-toggle="modal" data-target="#DeviceModal">&#9432;</button> </h3>
   Exposed surface area (cm<sup>2</sup>):
-  <input name="area" id="area" step="any" value="5.0" min="0.001" type="number"><br>
+  <input name="area" id="area" step="any" value="5.0" min="0.001" type="number" required><br>
   Exposure type: 
   <input type="radio" name="exposure" id="long-term" value="long-term" onclick="javascript:exposureCheck();" checked > long-term
   <input type="radio" name="exposure" id="prolonged" value="prolonged" onclick="javascript:exposureCheck();" > prolonged
   <input type="radio" name="exposure" id="limited" value="limited" onclick="javascript:exposureCheck();" > limited 
   <span id="limitedtime" style="visibility:hidden">
-    &nbsp; &rArr; Exposure time (h): <input name="exptime" id="time" step="any" min="0.001" max="24" value="24" type="number" ><br>
+    &nbsp; &rArr; Exposure time (h): <input name="exptime" id="time" step="any" min="0.001" max="24" value="24" type="number" required><br>
   </span>
 
 <!-- Modal -->
@@ -174,7 +169,6 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
   </div>
 </div>
 
-
 <!-- Assumptions input section -->
 
   <h3> Assumptions <button type=button class="Info_btn" data-toggle="modal" data-target="#AssumeModal">&#9432;</button> </h3>
@@ -209,12 +203,14 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
   </div>
 </div>
 
-
 <h3> Exposure assessment </h3>
 Click to screen your device: <button type="submit">Estimate exposure</button>
 
 </form>
 
+
+<p id="TestingOutput"> </p>
+
 <!-- Javascript to reveal/hide exposure time input box (limited contact) -->
 
 <script type="text/javascript">
@@ -226,10 +222,9 @@ function exposureCheck() {
         document.getElementById('time').value = '24';
     }
 }
+$(window).on('pageshow', function() { exposureCheck(); });
 </script>
 
 
-
-
 </body>
 </html>

color_module/templates/report.html

@@ -3,9 +3,10 @@
 <head>
     <meta charset="UTF-8">
     <title>CHRIS Report</title>
-<script src="https://polyfill.io/v3/polyfill.min.js?features=es6"></script>
-<script id="MathJax-script" async src="https://cdn.jsdelivr.net/npm/mathjax@3/es5/tex-mml-chtml.js"></script>
-<link rel= "stylesheet" type= "text/css" href= "{{ url_for('static',filename='styles.css') }}">
+
+    <script src="https://polyfill.io/v3/polyfill.min.js?features=es6"></script>
+    <script id="MathJax-script" async src="https://cdn.jsdelivr.net/npm/mathjax@3/es5/tex-mml-chtml.js"></script>
+    <link rel= "stylesheet" type= "text/css" href= "{{ url_for('static',filename='styles.css') }}">
 
 </head>
 
@@ -14,19 +15,20 @@
 <br clear="all" />
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) Report </h1>
+   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) Report </h1>
 </header>
 
 <body>
 
-<p> The following report was generated using CHRIS v.2.0 on
+<p> The following report was generated using CHRIS v.1.0 on 
 <script> document.write(new Date().toLocaleDateString()); </script>.
 </p>
 
-<h2>Exposure </h2>
+<h3>Exposure </h3>
 
 <p>
-<u> Diffusion calculation for {{chemName}} leaching from {{polymers[pIndex]}} estimates the worst case single day exposure = {{release}} mg. </u>
+<u> Diffusion calculation for {{chemName}} leaching from {{polymers[pIndex]}} estimates a worst case single day
+    exposure = {{release}} mg. </u>
 <p>
 
 <p>
@@ -35,12 +37,15 @@ This estimate was derived using solutions to the conservative plane sheet model
 \[
 M(\tau)= \left\{
   \begin{array}{cr} 
-      2 M_0 \sqrt{\tau/\pi} & \tau \leq 0.5 \\
-      M_0\left(1-8 \exp\left[-\tau \pi^2/4 \right]/\pi^2\right) & \tau > 0.5
+      2 M_0 \sqrt{\tau/\pi} & \tau \leq 0.2 \\
+      M_0\left(1-8 \exp\left[-\tau \pi^2/4 \right]/\pi^2\right) & \tau > 0.2
       \end{array} \right.
 \] 
 
-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:
+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>
@@ -51,18 +56,22 @@ where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and
 \( t \) = {{time}} h <br>
 <p>
 
-<h2> Assumptions </h2>
+<h3> Assumptions </h3>
 
 {% 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>
+<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>
+<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] %}
@@ -70,7 +79,8 @@ where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and
 {% endif %}
 
 {% if not assume[1] %}
-<font color="red"> &bull; Any color additive particles/aggregates are much smaller than the smallest component dimension (&le; 50x). <br> </font>
+<font color="red"> &bull; Any color additive particles/aggregates are much smaller than the smallest component dimension
+    (&le; 50x). <br> </font>
 {% endif %}
 
 {% if not assume[2] %}
@@ -87,18 +97,20 @@ where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and
 
 {% endif %}
 
-<h2> Screening level toxicological risk assessment </h2>
+<h3> Screening level toxicological risk assessment </h3>
 
 {% if caIndex > 10 %}
 
 <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}}.
+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>
+<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>
@@ -108,29 +120,37 @@ The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}
 {% 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>
+<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 %}
 
 {% else %}
 
-The tolerable intake value for your color additive is {{TI}} mg/kg/day.  Assuming a 50 kg patient, the tolerable exposure value would be {{50*TI}} mg/day.  Based on the exposure estimation this results in a margin of safety (MOS) of {{MOS}}.
+The tolerable intake value for your color additive is {{TI}} mg/kg/day.  Assuming a 50 kg patient, the tolerable
+exposure value would be {{50*TI}} mg/day.  Based on the exposure estimation this results in a margin of safety (MOS)
+of {{MOS}}.
 
 {% if MOS >= 1 %}
 
 <p>
-<font color="green"> The MOS based on the color additive specific TI is greater than one; therefore, no further analysis is needed for systemic biocompatibility endpoints.  </font>
+<font color="green"> The MOS based on the color additive specific TI is greater than one; therefore, no further analysis
+    is needed for systemic biocompatibility endpoints.  </font>
 </p>
 
 <p>
-<font color="red"> *Note*: This calculation assumes an adult patient population with a worst-case body weight of 50 kg.  If the intended patient population of your device is different, please adjust the tolerable exposure calculation accordingly. </font>
+<font color="red"> *Note*: This calculation assumes an adult patient population with a worst-case body weight of 50 kg.
+    If the intended patient population of your device is different, please adjust the tolerable exposure calculation
+    accordingly. </font>
 </p>
 
 {% else %}
 
 <p>
-<font color="red"> The MOS based on the color additive specific TI is less than one; therefore, further analysis is needed to address systemic biocompatibility endpoints.   </font>
+<font color="red"> The MOS based on the color additive specific TI is less than one; therefore, further analysis is
+    needed to address systemic biocompatibility endpoints.   </font>
 </p>
 
 {% endif %}
@@ -140,7 +160,10 @@ The tolerable intake value for your color additive is {{TI}} mg/kg/day.  Assumin
 {% if isCA == true %}
 
 <p>
-<font color="red"> *Note*: This assessment assumes that the color additive complies with all relevant medical device specific guidance documents and all relevant Code of Federal Regulations (CFR) color additive listings, if they exist for the color additive.  Examples of CFR listings are provided in the <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >FAQ</a>.</font>
+<font color="red"> *Note*: This assessment assumes that the color additive complies with all relevant medical device
+    specific guidance documents and all relevant Code of Federal Regulations (CFR) color additive listings, if they
+    exist for the color additive.  Examples of CFR listings are provided in the
+    <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >FAQ</a>.</font>
 </p>
 
 {% endif %}
@@ -151,24 +174,34 @@ The tolerable intake value for your color additive is {{TI}} mg/kg/day.  Assumin
 
 {% if iMOS >= 1 %}
 
-<font color="green"> The total color additive impurity level is {{impurity}} mg.  When compared to TTC this results in an MOS = {{iMOS}}. Therefore, no further analysis is needed for the impact of impurities on systemic biocompatibility endpoints. </font>
+<font color="green"> The total color additive impurity level is {{impurity}} mg.  When compared to TTC this results in
+    an MOS = {{iMOS}}. Therefore, no further analysis is needed for the impact of impurities on systemic
+    biocompatibility endpoints. </font>
 
 <p>
 <font color="red"> *Note*: This assessment assumes that any impurities present are not in the cohort of concern. </font>
 </p>
 
 <p>
-<font color="red"> *Note*: Users should review and confirm compliance of impurity levels with any relevant Code of Federal Regulations (CFR) listings as part of the submission package, i.e. in addition to any output of CHRIS.  A list of relevant CFR listings is provided <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >here</a>.</font>
+<font color="red"> *Note*: Users should review and confirm compliance of impurity levels with any relevant Code of
+    Federal Regulations (CFR) listings as part of the submission package, i.e. in addition to any output of CHRIS.
+    A list of relevant CFR listings is provided
+    <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >here</a>.</font>
 </p>
 
 {% else %}
 
-<font color="red"> The total color additive impurity level is {{impurity}} mg.  When compared to TTC this results in an MOS = {{iMOS}}. Therefore, further analysis is needed to address the impact of impurities on systemic biocompatibility endpoints. Guidance on alternative methods to address impurities is provided <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >here</a>. </font>
+<font color="red"> The total color additive impurity level is {{impurity}} mg.  When compared to TTC this results in
+    an MOS = {{iMOS}}. Therefore, further analysis is needed to address the impact of impurities on systemic
+    biocompatibility endpoints. Guidance on alternative methods to address impurities is provided
+    <a href="static/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >here</a>. </font>
 
 
 {% endif %}
 
 {% endif %}
 
+<button type="button" onclick="javascript:history.back()">Back</button>
+
 </body>
 </html>

exposure_module/static/exposure_COU.html

@@ -1,6 +1,8 @@
 <!DOCTYPE html>
 <html lang="en">
 <head>
+    <title>Bulk-COU</title>
+    <link rel="stylesheet" href="../../static/styles.css">
     <meta charset="UTF-8">
 </head>
 

exposure_module/static/exposure_COU.md

@@ -2,6 +2,8 @@
 <!DOCTYPE html>
 <html lang="en">
 <head>
+    <title>Bulk-COU</title>
+    <link rel="stylesheet" href="../../static/styles.css">
     <meta charset="UTF-8">
 </head>
 

exposure_module/templates/exposure_index.html

@@ -208,6 +208,7 @@ function exposureCheck() {
         document.getElementById('time').value = '24';
     }
 }
+$(window).on('pageshow', function() { exposureCheck(); });
 </script>
 
 </body>

functions.py

@@ -12,21 +12,31 @@ def SigFigs(number, n):
     return round(number, n - int(math.floor(math.log10(math.fabs(number)))) - 1)
 
 def Piringer(Mw, Ap):
+
     if Mw > 1100.:
         Mw = 1100.
-    return 1e4 * np.exp(Ap - 0.1351 * Mw ** (2. / 3.) + 0.003 * Mw - 10454. / 310.)
+    T = 310.
+
+    # Semi-empirical model for D(Mw) given polymer property Ap- Toxicol. Sci. 2019, 172 (1), 201–212.
+    return 1e4 * np.exp(Ap - 0.1351 * Mw ** (2. / 3.) + 0.003 * Mw - 10454. / T)
 
 def WilkeChang(Mw):
+    # Semi-empirical model for D(Mw) assuming diffusion in water
+    Va = 4.76 + 1.32 * Mw # molecular volume as a function of Mw assuming linear alkanes as worst case
+    T = 310.
+    MwH2O = 18.
+    viscosity = 0.6913
+    alpha = 2.6
 
-    Va = 4.76 + 1.32 * Mw
-    return 7.4e-8 * (18. * 2.6) ** 0.5 * 310. / 0.6913 / Va ** 0.6
+    return 7.4e-8 * (MwH2O * alpha) ** 0.5 * T / viscosity / Va ** 0.6
 
 def SheetRelease(amount, vol, area, time, D):
 
+    # analytical solution(s) to Fick's law for a plane sheet
     L = vol / area
-    D = D * 3600.
-    tau = D * time / L ** 2.
-    if tau <= 0.5:
+    D = D * 3600. # convert seconds to hours
+    tau = D * time / L ** 2. # dimensionless time
+    if tau <= 0.2:
         release = 2. * amount * np.sqrt(tau / np.pi)
     else:
         release = amount * (1. - (8. / (np.pi ** 2.)) * np.exp(-tau * np.pi ** 2. / 4.))

templates/chemError.html

@@ -0,0 +1,23 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <meta charset="UTF-8">
+    <title>CHRIS</title>
+
+</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" />
+
+<body>
+
+<div style="font-size:5rem;text-align:center"> &#129318; </div>
+
+<p style="font-size:2rem;text-align:center">
+    Uh-oh! Something went wrong. We were unable to match your chemical.  Please return to the previous page and try a
+    different identifier.
+</p>
+
+
+</body>