incorporating Echo feedback

color3_module/colors.py

@@ -71,6 +71,10 @@ def app_post():
     caIndex = (np.where(CAs == CA)[0])[0]
 
     TI = caData[caIndex][1]
+    units = request.form['units']
+    if units == 'µg':
+        TI *= 1000
+
     impurity = 1.
     isCA = True
     chemName = ''
@@ -130,6 +134,9 @@ def app_post():
     else:
         TTC = 0.0015
 
+    if units == 'µg':
+        TTC *= 1000
+
     polytg = ''
     use_qrf = False
     if polymer == 'Other polymer':
@@ -185,7 +192,7 @@ def app_post():
     #print(release_list, file=sys.stderr)
     frac_list = [str(SigFigs(r/amount*100,2))+'%' for r in release_list]
     release_list = [SigFigs(r,2) for r in release_list]
-    df_rel = pd.DataFrame(np.transpose([tlist,release_list,frac_list]),columns=['Exposure time (days)','Cumulative release (mg)','Cumulative release (%)'])
+    df_rel = pd.DataFrame(np.transpose([tlist,release_list,frac_list]),columns=['Exposure time (days)',f'Cumulative release ({units})','Cumulative release (%)'])
     df_rel['Exposure time (days)'] = df_rel['Exposure time (days)'].astype(float)
     release_table = df_rel.sort_values(by='Exposure time (days)').to_html(index=False)
 
@@ -200,7 +207,7 @@ def app_post():
     #pngImageB64String = RatePlot(tarray, rates)
 
     return render_template('color3_report.html', caIndex=caIndex, TI=TI, isCA=isCA, show_properties=show_properties, polymers=polymers, pIndex=pIndex, release=release, release_table=release_table,
-                           area=area, vol=vol, amount=amount, diff=diff, time=time, exposure=exposure, TTC=TTC,
+                           area=area, vol=vol, amount=amount, diff=diff, time=time, exposure=exposure, TTC=TTC, units=units,
                            MOS=MOS, chemName=chemName, MW=MW, LogP=LogP, rho=rho, mp=mp, iupac=iupac, cas=cas, smiles=smiles, molImage=molImage,
                            ceramic=is_ceramic, impurity=impurity, iMOS=iMOS, methods=[method,polytg,density])
 

color3_module/templates/color3_index.html

@@ -46,7 +46,11 @@ Identity: <select name="CA" id="CA" onchange="javascript:caCheck();">
   Identifier: <input name="chemName" id="chemName" type="text" value="">
   </span> <br>
 
-Amount (mg): <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number" required> <br>
+  Amount: <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number" required> 
+  Amount units: <select name="units">
+    <option value="µg" selected>µg</option>
+    <option value="mg" >mg</option>
+  </select> <br>
 
 Total impurity concentration (%): <input name="impurity" id="impurity" value="0.1" step="any" min="0.000001" max='100.0' type="number" required> <br>
 
@@ -91,7 +95,8 @@ $(window).on('pageshow', function() { caCheck(); });
             Alternatively, CHRIS can attempt to identify the chemical using a common name for the chemical.
           If you are evaluating an additive associated with a color additive please select "Other color additive associated compound" and
           follow the same procedure for "Other color additive".
-        <p><em>Amount</em> - Enter the total mass of the substance in the component being evaluated expressed in milligrams.</p>
+        <p><em>Amount</em> - Enter the total mass of the substance in the component being evaluated expressed in micrograms or milligrams.</p>
+        <p><em>Amount units</em> - Select the appropriate units for the amount, micrograms (µg) or milligrams (mg).</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>
       </div>
       <div class="modal-footer">
@@ -151,7 +156,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
   <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" required><br>
+    &nbsp; &rArr; Exposure duration (h): <input name="exptime" id="time" step="any" min="0.001" max="24" value="24" type="number" required><br>
   </span>
 
 <!-- Modal -->
@@ -165,7 +170,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
       </div>
       <div class="modal-body">
         <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: > 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.</p>
+        <p><em>Exposure type</em> - 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 duration in hours.</p>
       </div>
       <div class="modal-footer">
         <button type="button" class="btn btn-default" data-dismiss="modal">Close</button>
@@ -176,7 +181,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
 </div>
 
 <h3> Exposure assessment <button type=button class="Info_btn" data-toggle="modal" data-target="#ExposureModal">&#9432;</button> </h3>
-  Cumulative exposure time(s): 
+  Cumulative exposure duration(s): 
   <input type="checkbox" id="exposure1d" name="exposure1d" value="exposure1d" checked=True, disabled=True>
   <label for="exposure1d">1 day</label>
   <input type="checkbox" id="exposure30d" name="exposure30d" value="exposure30d" checked=True>
@@ -199,8 +204,9 @@ Click to screen your device: <button type="submit">Estimate exposure</button>
         <h4 class="modal-title">Exposure assessment</h4>
       </div>
       <div class="modal-body">
-        <p><em>Cumulative exposure time(s)</em> Check the boxes for the exposure time(s) to use for cumulative release estimates. 1-day exposure is always calculated.
-        If the "Other duration" box is checked, enter the desired exposure time in days.</p>
+        <p><em>Cumulative exposure duration(s)</em> Check the boxes for the exposure duration(s) to use for cumulative release estimates. 1-day exposure is always calculated.
+        If the "Other duration" box is checked, enter the desired exposure duration in days (e.g., the maximum use duration of the device). 
+        Note that this calculation assumes a single device is used for the entire duration. If multiple devices are used concurrently or sequentially (e.g., daily replacement), this should be accounted for during toxicological risk assessment.</p>
       </div>
       <div class="modal-footer">
         <button type="button" class="btn btn-default" data-dismiss="modal">Close</button>
@@ -229,7 +235,7 @@ function polymerCheck() {
 $(window).on('pageshow', function() { polymerCheck(); });
 </script>
 
-<!-- Javascript to reveal/hide exposure time input box (limited contact) -->
+<!-- Javascript to reveal/hide exposure duration input box (limited contact) -->
 
 <script type="text/javascript">
 function exposureCheck() {

color3_module/templates/color3_report.html

@@ -32,6 +32,10 @@
 
 </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 - Color additives (v3)</h1>
 </header>
@@ -71,16 +75,16 @@
 <p>
 {% if methods[0]=="category" %}
 <u> Diffusion calculation for leaching from {{polymers[pIndex]}} estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="wc" %}
 <u> Diffusion calculation for leaching from the polymer (with worst-case diffusion in water assumed because no T<sub>g</sub> was specified) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="qrf" %}
 <u> Diffusion calculation for leaching from the polymer (with density = {{methods[2]}} g/cm<sup>3</sup> and T<sub>g</sub> = {{methods[1]}} &deg;C) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="qrf/wc" %}
 <u> Diffusion calculation for leaching from the polymer (with worst-case diffusion in water assumed because this system is outside the model training domain) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% endif %}
 <p>
 
@@ -104,13 +108,13 @@ where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and
 <p>
 \( A \) = {{area}} cm<sup>2</sup> <br>
 \( V \) = {{vol}} cm<sup>3</sup> <br>
-\( M_0 \) = {{amount}} mg <br>
+\( M_0 \) = {{amount}} {{units}} <br>
 \( D \) = {{diff}} cm<sup>2</sup>/s <br>
 \( t \) = {{time}} h <br>
 <p>
 
 <p>
-It can be helpful to examine the cumulative amount released over various exposure times:
+It can be helpful to examine the cumulative amount released over various exposure times. For example, the 30-day cumulative exposure may be compared to the TSL<sub>&le;30 d</sub> as recommended in ISO 10993-17:2023. Note that this calculation assumes a single device is used for the entire duration. If multiple devices are used concurrently or sequentially (e.g., daily replacement), this should be accounted for during toxicological risk assessment.
 </p>
 
 <div>
@@ -124,7 +128,7 @@ It can be helpful to examine the cumulative amount released over various exposur
 {% if caIndex > 10 %}
 
 <p>
-The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}} mg.  Based on the exposure estimation
+The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}} {{units}}/day.  Based on the exposure estimation
     this results in a margin of safety (MOS) of {{MOS}}.
 </p>
 
@@ -135,6 +139,10 @@ The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}
     for systemic biocompatibility endpoints.  </font>
 </p>
 
+<p>
+<font color="red"> *Note*: This assessment assumes that the amount (\( M_0 \)) accounts for the number of devices used concurrently (i.e., multiply the per-device amount by the number of devices used concurrently). </font>
+</p>
+
 <p>
 <font color="red"> *Note*: This assessment assumes that the chemical is not in the cohort of concern. </font>
 </p>
@@ -151,8 +159,8 @@ The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}
 
 {% 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)
+The tolerable intake value for your color additive is {{TI}} {{units}}/kg/day.  Assuming a 50 kg patient, the tolerable
+exposure value would be {{50*TI}} {{units}}/day.  Based on the exposure estimation this results in a margin of safety (MOS)
 of {{MOS}}.
 
 {% if MOS >= 1 %}
@@ -162,6 +170,10 @@ of {{MOS}}.
     is needed for systemic biocompatibility endpoints.  </font>
 </p>
 
+<p>
+<font color="red"> *Note*: This assessment assumes that the amount (\( M_0 \)) accounts for the number of devices used concurrently (i.e., multiply the per-device amount by the number of devices used concurrently). </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
@@ -194,10 +206,14 @@ of {{MOS}}.
 
 {% if iMOS >= 1 %}
 
-<font color="green"> The total additive impurity level is {{impurity}} mg.  When compared to TTC this results in
+<font color="green"> The total additive impurity level is {{impurity}} {{units}}.  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 the amount (\( M_0 \)) accounts for the number of devices used concurrently (i.e., multiply the per-device amount by the number of devices used concurrently). </font>
+</p>
+
 <p>
 <font color="red"> *Note*: This assessment assumes that any impurities present are not in the cohort of concern. </font>
 </p>
@@ -214,7 +230,7 @@ of {{MOS}}.
 {% else %}
 
 <p>
-<font color="red"> The total additive impurity level is {{impurity}} mg.  When compared to TTC this results in
+<font color="red"> The total additive impurity level is {{impurity}} {{units}}.  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="color_module/FAQ.html#how-does-chris-deal-with-color-additive-impurities" >here</a>. </font>

exposure3_module/exposure.py

@@ -109,6 +109,10 @@ def exp_post():
     else:
         TTC = 0.0015
 
+    units = request.form['units']
+    if units == 'µg':
+        TTC *= 1000
+
     polytg = ''
     use_qrf = False
     if polymer == 'Other polymer':
@@ -162,7 +166,7 @@ def exp_post():
     #print(release_list, file=sys.stderr)
     frac_list = [str(SigFigs(r/amount*100,2))+'%' for r in release_list]
     release_list = [SigFigs(r,2) for r in release_list]
-    df_rel = pd.DataFrame(np.transpose([tlist,release_list,frac_list]),columns=['Exposure time (days)','Cumulative release (mg)','Cumulative release (%)'])
+    df_rel = pd.DataFrame(np.transpose([tlist,release_list,frac_list]),columns=['Exposure time (days)',f'Cumulative release ({units})','Cumulative release (%)'])
     df_rel['Exposure time (days)'] = df_rel['Exposure time (days)'].astype(float)
     release_table = df_rel.sort_values(by='Exposure time (days)').to_html(index=False)
 
@@ -171,7 +175,7 @@ def exp_post():
     diff = SigFigs(diff, 2)
 
     return render_template('exposure3_report.html', show_properties=show_properties, polymers=polymers, pIndex=pIndex, release=release, release_table=release_table,
-                           area=area, vol=vol, amount=amount, diff=diff, time=time, exposure=exposure, TTC=TTC,
+                           area=area, vol=vol, amount=amount, diff=diff, time=time, exposure=exposure, TTC=TTC, units=units,
                            MOS=MOS, chemName=chemName, MW=MW, LogP=LogP, rho=rho, mp=mp, iupac=iupac, cas=cas, smiles=smiles, molImage=molImage,
                            LogP_origin=LogP_origin, rho_origin=rho_origin, mp_origin=mp_origin, ceramic=is_ceramic, methods=[method,polytg,density])
 

exposure3_module/templates/exposure3_index.html

@@ -41,7 +41,11 @@ For a history of updates, please see the <a href="{{url_for('.static', filename=
 
   Identifier: <input name="chemName" id="chemName" type="text" value="" required><br>
 
-  Amount (mg): <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number" required> <br>
+  Amount: <input name="amount" id="amount" value="1.0" step="any" min="0.000001" type="number" required> 
+  Amount units: <select name="units">
+    <option value="µg" selected>µg</option>
+    <option value="mg" >mg</option>
+  </select> <br>
 
   <!-- Modal -->
   <div id="LeachModal" class="modal fade" role="dialog">
@@ -59,7 +63,8 @@ For a history of updates, please see the <a href="{{url_for('.static', filename=
             be found for many chemicals using <a href="https://pubchem.ncbi.nlm.nih.gov">PubChem</a> or generated based on
             the molecular structure using tools such as <a href="https://cactus.nci.nih.gov/cgi-bin/osra/index.cgi">OSRA</a>.
             Alternatively, CHRIS can attempt to identify the chemical using a common name for the chemical.</p>
-          <p><em>Amount</em> - Enter the total mass of the substance in the component being evaluated expressed in milligrams.</p>
+          <p><em>Amount</em> - Enter the total mass of the substance in the component being evaluated expressed in micrograms or milligrams.</p>
+          <p><em>Amount units</em> - Select the appropriate units for the amount, micrograms (µg) or milligrams (mg).</p>
         </div>
         <div class="modal-footer">
           <button type="button" class="btn btn-default" data-dismiss="modal">Close</button>
@@ -118,7 +123,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
   <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" required><br>
+    &nbsp; &rArr; Exposure duration (h): <input name="exptime" id="time" step="any" min="0.001" max="24" value="24" type="number" required><br>
   </span>
 
 <!-- Modal -->
@@ -134,7 +139,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
         <p><em>Exposed surface area</em> - Enter the patient contacting surface area of the 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: > 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.</p>
+          For limited exposures (&#8804; 24 hours), please enter the maximum exposure duration in hours.</p>
       </div>
       <div class="modal-footer">
         <button type="button" class="btn btn-default" data-dismiss="modal">Close</button>
@@ -145,7 +150,7 @@ Density (g/cm<sup>3</sup>): <input name="density" id="density" step="any" value=
 </div>
 
 <h3> Exposure assessment <button type=button class="Info_btn" data-toggle="modal" data-target="#ExposureModal">&#9432;</button> </h3>
-  Cumulative exposure time(s): 
+  Cumulative exposure duration(s): 
   <input type="checkbox" id="exposure1d" name="exposure1d" value="exposure1d" checked=True, disabled=True>
   <label for="exposure1d">1 day</label>
   <input type="checkbox" id="exposure30d" name="exposure30d" value="exposure30d" checked=True>
@@ -168,8 +173,9 @@ Click to screen your device: <button type="submit">Estimate exposure</button>
         <h4 class="modal-title">Exposure assessment</h4>
       </div>
       <div class="modal-body">
-        <p><em>Cumulative exposure time(s)</em> Check the boxes for the exposure time(s) to use for cumulative release estimates. 1-day exposure is always calculated.
-        If the "Other duration" box is checked, enter the desired exposure time in days.</p>
+        <p><em>Cumulative exposure duration(s)</em> Check the boxes for the exposure duration(s) to use for cumulative release estimates. 1-day exposure is always calculated.
+        If the "Other duration" box is checked, enter the desired exposure duration in days (e.g., the maximum use duration of the device). 
+        Note that this calculation assumes a single device is used for the entire duration. If multiple devices are used concurrently or sequentially (e.g., daily replacement), this should be accounted for during toxicological risk assessment.</p>
       </div>
       <div class="modal-footer">
         <button type="button" class="btn btn-default" data-dismiss="modal">Close</button>
@@ -195,7 +201,7 @@ function polymerCheck() {
 $(window).on('pageshow', function() { polymerCheck(); });
 </script>
 
-<!-- Javascript to reveal/hide exposure time input box (limited contact) -->
+<!-- Javascript to reveal/hide exposure duration input box (limited contact) -->
 
 <script type="text/javascript">
 function exposureCheck() {

exposure3_module/templates/exposure3_report.html

@@ -74,16 +74,16 @@
 <p>
 {% if methods[0]=="category" %}
 <u> Diffusion calculation for leaching from {{polymers[pIndex]}} estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="wc" %}
 <u> Diffusion calculation for leaching from the polymer (with worst-case diffusion in water assumed because no T<sub>g</sub> was specified) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="qrf" %}
 <u> Diffusion calculation for leaching from the polymer (with density = {{methods[2]}} g/cm<sup>3</sup> and T<sub>g</sub> = {{methods[1]}} &deg;C) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% elif methods[0]=="qrf/wc" %}
 <u> Diffusion calculation for leaching from the polymer (with worst-case diffusion in water assumed because this system is outside the model training domain) estimates a worst case single day
-    exposure = {{release}} mg. </u>
+    exposure = {{release}} {{units}}. </u>
 {% endif %}
 <p>
 
@@ -104,13 +104,13 @@ where \( \tau= D t A^2 / V^2 \) and \( A \) and \( V \) are the surface area and
 <p>
 \( A \) = {{area}} cm<sup>2</sup> <br>
 \( V \) = {{vol}} cm<sup>3</sup> <br>
-\( M_0 \) = {{amount}} mg <br>
+\( M_0 \) = {{amount}} {{units}} <br>
 \( D \) = {{diff}} cm<sup>2</sup>/s <br>
 \( t \) = {{time}} h <br>
 </p>
 
 <p>
-It can be helpful to examine the cumulative amount released over various exposure times:
+It can be helpful to examine the cumulative amount released over various exposure times. For example, the 30-day cumulative exposure may be compared to the TSL<sub>&le;30 d</sub> as recommended in ISO 10993-17:2023. Note that this calculation assumes a single device is used for the entire duration. If multiple devices are used concurrently or sequentially (e.g., daily replacement), this should be accounted for during toxicological risk assessment.
 </p>
 
 <div>
@@ -122,7 +122,7 @@ It can be helpful to examine the cumulative amount released over various exposur
 <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}}.
+The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}} {{units}}/day.  Based on the exposure estimation this results in a margin of safety (MOS) of {{MOS}}.
 </p>
 
 {% if MOS >= 1 %}
@@ -131,6 +131,10 @@ The threshold for toxicological concern (TTC) for {{exposure}} contact is {{TTC}
 <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 amount (\( M_0 \)) accounts for the number of devices used concurrently (i.e., multiply the per-device amount by the number of devices used concurrently). </font>
+</p>
+
 <p>
 <font color="red"> *Note*: This assessment assumes that the chemical is not in the cohort of concern. </font>
 </p>