7.0 RELIABILITY OF THE 3T3 AND NHK NRU TEST METHODS 7-3

7.1 Substances Used to Determine the Reliability of the 3T3 and NHK\
NRU Test Methods 7-4

7.2 Reproducibility Analyses for the 3T3 and NHK NRU Test Methods 7-6

> 7.2.1 ANOVA Results for the 3T3 and NHK NRU Test Methods 7-6
>
> 7.2.2 CV Results for the 3T3 and NHK NRU Test Methods 7-17
>
> 7.2.3 Comparison of Laboratory-Specific Linear Regression Analyses for
> the Prediction of *In Vivo* Rodent LD~50~ Values from *In Vitro* NRU
> IC~50~ Values 7-24
>
> 7.2.4 Laboratory Concordance for the Prediction of GHS Acute Oral
> Toxicity Category 7-24

7.3 Historical Positive Control Data 7-27

> 7.3.1 ANOVA and Linear Regression Results for the 3T3 NRU\
> Test Method 7-30
>
> 7.3.2 ANOVA and Linear Regression Results for the NHK NRU\
> Test Method 7-32

7.4 Laboratory Concordance for Solvent Selection 7-34

7.5 Summary 7-37

***\[This Page Intentionally Left Blank\]***

7.0 RELIABILITY OF THE 3T3 AND NHK NRU TEST METHODS

This section discusses the reliability of the 3T3 and NHK NRU test
methods. Reliability is the degree to which a test method can be
performed reproducibly within and among laboratories over time (ICCVAM
2003). It is assessed by calculating intra- and inter-laboratory
reproducibility and repeatability. Reproducibility is the consistency of
individual test results obtained in a single laboratory (intralaboratory
reproducibility) or in different laboratories (interlaboratory
reproducibility) using the same protocol and test samples.
Repeatability, usually applied to results within a laboratory, is the
closeness of agreement between test results obtained within a single
laboratory when the procedure is performed on the same substance under
identical conditions within a given time. The NICEATM/ECVAM study was
not designed to assess intralaboratory repeatability.

For the NICEATM/ECVAM validation study, reliability was assessed by
determining both intra- and inter-laboratory reproducibility.
Intralaboratory reproducibility is the agreement of results produced
when qualified people within the same laboratory perform the test method
using the same test protocol at different times (ICCVAM 2003).
Interlaboratory reproducibility is the agreement of results from
different qualified laboratories using the same protocol and reference
substances. Interlaboratory reproducibility indicates the extent to
which a test method can be successfully transferred among laboratories.

Intra- and inter-laboratory reproducibility of the 3T3 and NHK NRU test
methods were determined using ANOVA and CV analysis as discussed in
**Section 5.3.3 (**see **Sections 7.2.1** and **7.2.2**).
Interlaboratory reproducibility of the 3T3 and NHK NRU test methods was
also assessed by comparing the laboratory-specific IC~50~-LD~50~
regressions (from **Table 6-1**) to one another for each test method
(see **Section 7.2.3**) and by evaluating laboratory concordance for the
GHS acute oral toxicity category predictions reported in **Sections
6.3.1** through **6.3.3** (see **Section 7.2.4**). Laboratory
concordance for the solvent selection process using the solubility
protocol (described in **Section 2.9**) is provided in **Section 7.4**.

**7.1 Substances Used to Determine the Reliability of the 3T3 and NHK
NRU Test Methods**

The SMT intended to use the IC~50~ results of all 72 reference
substances identified for testing in **Table 3-2** to determine the
reliability of the 3T3 and NHK NRU test methods. Unfortunately, IC~50~
results for all substances could not be obtained in all the
laboratories. **Table 7-1** shows the substances that failed to yield
sufficient cytotoxicity for the calculation of an IC~50~ and the number
of substances left to determine intralaboratory reproducibility. The
laboratories failed to obtain IC~50~ results for three to five
substances in the 3T3 NRU test method and two to three substances with
the NHK NRU test method.

For the 3T3 NRU test method, no laboratory achieved sufficient
cytotoxicity to obtain IC~50~ values for carbon tetrachloride or
methanol and only one laboratory obtained IC~50~ results for lithium
carbonate and xylene. Thus, interlaboratory reproducibility for the 3T3
NRU test method was assessed using the remaining 68 reference
substances. For the NHK NRU test method, no laboratory obtained IC~50~
values for carbon tetrachloride and only one laboratory achieved IC~50~
results for xylene and 1,1,1-trichloroethane. Interlaboratory
reproducibility for the NHK NRU test method was assessed using the
IC~50~ results for the remaining 69 reference substances.

Despite the fact that IC~50~ values were not obtained by all the
laboratories for all reference substances, **Table 7-2** shows that the
complete range of LD~50~ responses, as defined by the GHS classification
for acute oral toxicity in **Table 3-1**, was covered by the remaining
substances. The IC~50~ values also covered a wide range of responses
(see **Table 7-3**). IC~50~ values for the 3T3 NRU test method ranged
from 0.005 to 38,878 μg/mL. IC~50~ values for the NHK NRU test method
covered a larger range, from 0.00005 to 49,800 μg/mL.

**Table 7-1 Reference Substances That Failed to Yield IC~50~ Values^1^
And Number of Reference Substances Available for Intralaboratory
Reproducibility Analyses**

+-----------+----------------------+----+-----------------------+----+
| **Lab     | **3T3 NRU Test       |    | **NHK NRU Test        |    |
| oratory** | Method**             |    | Method**              |    |
+-----------+----------------------+----+-----------------------+----+
|           | **Reference          | ** | **Reference           | ** |
|           | Substances Lacking   | N^ | Substances Lacking    | N^ |
|           | IC~50~ Results**     | 2^ | IC~50~ Results**      | 2^ |
|           |                      | ** |                       | ** |
+-----------+----------------------+----+-----------------------+----+
| ECBC      | Carbon tetrachloride | 69 | Carbon tetrachloride  | 69 |
|           |                      |    |                       |    |
|           | Methanol             |    | Methanol              |    |
|           |                      |    |                       |    |
|           | Xylene               |    | Xylene                |    |
+-----------+----------------------+----+-----------------------+----+
| FAL       | Carbon tetrachloride | 67 | 1,1,1-Trichloroethane | 69 |
|           |                      |    |                       |    |
|           | Gibberellic acid     |    | Carbon tetrachloride  |    |
|           |                      |    |                       |    |
|           | Lithium carbonate    |    | Xylene                |    |
|           |                      |    |                       |    |
|           | Methanol             |    |                       |    |
|           |                      |    |                       |    |
|           | Xylene               |    |                       |    |
+-----------+----------------------+----+-----------------------+----+
| IIVS      | Carbon tetrachloride | 69 | 1,1,1-Trichloroethane | 70 |
|           |                      |    |                       |    |
|           | Lithium carbonate    |    | Carbon tetrachloride  |    |
|           |                      |    |                       |    |
|           | Methanol             |    |                       |    |
+-----------+----------------------+----+-----------------------+----+

> ^1^Due to insufficient cytotoxicity.
>
> ^2^Number of substances available for intralaboratory reproducibility
> analyses.

**Table 7-2 Number of Reference Substances Tested vs Number of Reference
Substances Yielding IC~50~ Values in Each** **GHS Toxicity Category^1^
for Two Sets of LD~50~** Values

+--------------+-----+-------+----------+--------+----------+--------+
| **GHS        | **I | *     | *        |        | *        |        |
| C            | nit | *Refe | *Results |        | *Results |        |
| ategory^1^** | ial | rence | from 3T3 |        | from NHK |        |
|              | O   | Oral  | NRU**    |        | NRU Test |        |
| **(LD~50~ in | ral | L     |          |        | Method** |        |
| mg/kg)**     | LD  | D~50~ | **Test   |        |          |        |
|              | ~50 | ^3^** | Method** |        |          |        |
|              | ~^2 |       |          |        |          |        |
|              | ^** |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+
|              |     |       | *        | **Ref  | *        | **Ref  |
|              |     |       | *Initial | erence | *Initial | erence |
|              |     |       | Oral     | Oral   | Oral     | Oral   |
|              |     |       | LD~      | LD~50  | LD~      | LD~50  |
|              |     |       | 50~^2^** | ~^3^** | 50~^2^** | ~^3^** |
+--------------+-----+-------+----------+--------+----------+--------+
| LD~50~ ≤ 5   | 12  | 7     | 12       | 7      | 12       | 7      |
+--------------+-----+-------+----------+--------+----------+--------+
| 5 \< LD~50~  | 12  | 12    | 12       | 12     | 12       | 12     |
| ≤ 50         |     |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+
| 50 \< LD~50~ | 12  | 12    | 12       | 12     | 12       | 12     |
| ≤ 300        |     |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+
| 300 \<       | 12  | 16    | 11       | 15     | 12       | 16     |
| LD~50~ ≤     |     |       |          |        |          |        |
| 2000         |     |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+
| 2000 \<      | 12  | 12    | 10       | 10     | 10       | 10     |
| LD~50~ ≤     |     |       |          |        |          |        |
| 5000         |     |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+
| LD~50~ \>    | 12  | 13    | 11       | 12     | 11       | 12     |
| 5000         |     |       |          |        |          |        |
+--------------+-----+-------+----------+--------+----------+--------+

^1^GHS-Globally Harmonized System of Classification and Labelling of
Chemicals (UN 2005).

^2^Number of reference substances that yielded an IC~50~ value in at
least one laboratory based on initial oral LD~50~ in **Table 3-2**.
Initial oral LD~50~ values, used during the reference substance
selection process, were those used by the Registry of Cytotoxicity (RC)
(from 1983/84 RTECS^®^) when applicable. The RC is a database of acute
oral LD~50~ values for rats and mice obtained from RTECS^®^ and IC~50~
values from *in vitro* cytotoxicity assays using multiple cell lines and
cytotoxicity endpoints for chemicals with known molecular weights (Halle
1998).

Values for reference substances not included in the RC came from HSDB or
RTECS^®^.

^3^Number of reference substances that yielded an IC~50~ value in at
least one laboratory based on reference oral LD~50~ in **Table 4-2**.
Reference oral LD~50~ values from rats and mice were derived after
evaluating LD~50~ values located through literature searches and
references from toxicity databases such as RTECS^®^.

**7.2 Reproducibility Analyses for the 3T3 and NHK NRU Test Methods**

Reproducibility of the 3T3 and NHK NRU test methods were performed using
ANOVA and CV as described in **Section 5.3.3**. **Table 7-3** reports
the results of these analyses for each reference substance and test
method.

7.2.1 [ANOVA Results for the 3T3 and NHK NRU Test Methods]{.underline}

ANOVA was performed as discussed in Section **5.3.3**. Since the sample
sizes from this study were small, usually three observations per
laboratory, the ANOVA results may be misleading. There may be some
differences that are statistically significant only because there are
too few observations within the laboratories to adequately characterize
the variability, and/or the within-laboratory variability estimate is
small.

*Differences Among the Laboratories for the 3T3 NRU Test Method*

The ANOVA results in **Table 7-3** indicate that there were
statistically significant (p \< 0.01) differences among the laboratories
for 26 reference substances. These chemicals are listed in **Table 7-4**
along with columns showing the laboratory statistically significantly
differing from the other two laboratories (as indicated by the contrast
results). Since significant laboratory differences may be produced by
insolubility or volatility, **Table 7-4** also indicates whether any
laboratory reported insolubility or volatility during conduct of the
test. Insolubility was suggested by the presence of precipitates in
either the stock solutions or in cell culture. Volatility was identified
by the use of plate sealers to contain volatile contamination of lower
concentration wells by higher concentrations. Insolubility and
volatility were reported for only nine of the 26 chemicals.

<table>
<colgroup>
<col style="width: 13%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="13"><strong>Table 7-3 Reproducibility Results for the 3T3
and NHK NRU Test Methods</strong></th>
</tr>
<tr class="odd">
<th rowspan="5"><strong>Reference Substance/Laboratory</strong></th>
<th colspan="6"><strong>3T3 NRU Test Method</strong></th>
<th colspan="6"><strong>NHK NRU Test Method</strong></th>
</tr>
<tr class="header">
<th rowspan="4"><strong>Arithmetic Mean IC<sub>50</sub>
(μg/mL)<sup>1</sup></strong></th>
<th rowspan="4"><strong>Arithmetic IntraLab %CV</strong></th>
<th rowspan="4"><strong>Arithmetic InterLab %CV</strong></th>
<th rowspan="4"><strong>Log Arithmetic Mean IC<sub>50</sub>
(μg/mL)<sup>1</sup></strong></th>
<th rowspan="4"><strong>ANOVA P<sup>2</sup></strong></th>
<th rowspan="4"><p><strong>Contrast</strong></p>
<p><strong>P<sup>3</sup></strong></p></th>
<th rowspan="4"><strong>Arithmetic Mean IC<sub>50</sub>
(μg/mL)<sup>1</sup></strong></th>
<th rowspan="4"><strong>Arithmetic IntraLab %CV</strong></th>
<th rowspan="4"><strong>Arithmetic InterLab %CV</strong></th>
<th rowspan="4"><strong>Log Arithmetic Mean IC<sub>50</sub>
(μg/mL)<sup>1</sup></strong></th>
<th rowspan="4"><strong>ANOVA P<sup>2</sup></strong></th>
<th rowspan="4"><p><strong>Contrast</strong></p>
<p><strong>P<sup>3</sup></strong></p></th>
</tr>
<tr class="odd">
</tr>
<tr class="header">
</tr>
<tr class="odd">
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Acetaminophen</td>
<td>50.1</td>
<td> </td>
<td>28</td>
<td>1.70</td>
<td>0.171</td>
<td> </td>
<td>526</td>
<td> </td>
<td>13</td>
<td>2.72</td>
<td>0.181</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>40.8</td>
<td>22</td>
<td> </td>
<td>1.61</td>
<td> </td>
<td>NA</td>
<td>558</td>
<td>15</td>
<td> </td>
<td>2.75</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>66.2</td>
<td>35</td>
<td> </td>
<td>1.82</td>
<td> </td>
<td>NA</td>
<td>447</td>
<td>19</td>
<td> </td>
<td>2.65</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>43.4</td>
<td>26</td>
<td> </td>
<td>1.64</td>
<td> </td>
<td>NA</td>
<td>571</td>
<td>14</td>
<td> </td>
<td>2.76</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Acetonitrile</td>
<td>8484</td>
<td> </td>
<td>21</td>
<td>3.93</td>
<td>0.553</td>
<td> </td>
<td>10104</td>
<td> </td>
<td>8</td>
<td>4.00</td>
<td>0.9641</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>6433</td>
<td>2</td>
<td> </td>
<td>3.81</td>
<td> </td>
<td>NA</td>
<td>10868</td>
<td>72</td>
<td> </td>
<td>4.04</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>9690</td>
<td>58</td>
<td> </td>
<td>3.99</td>
<td> </td>
<td>NA</td>
<td>10153</td>
<td>19</td>
<td> </td>
<td>4.01</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>9330</td>
<td>13</td>
<td> </td>
<td>3.97</td>
<td> </td>
<td>NA</td>
<td>9290</td>
<td>4</td>
<td> </td>
<td>3.97</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Acetylsalicylic acid</td>
<td>760</td>
<td> </td>
<td>56</td>
<td>2.88</td>
<td>&lt;0.001</td>
<td> </td>
<td>613</td>
<td> </td>
<td>15</td>
<td>2.79</td>
<td>0.060</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>646</td>
<td>10</td>
<td> </td>
<td>2.81</td>
<td> </td>
<td>0.581</td>
<td>631</td>
<td>3</td>
<td> </td>
<td>2.80</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>1234</td>
<td>24</td>
<td> </td>
<td>3.09</td>
<td> </td>
<td>&lt;0.001</td>
<td>694</td>
<td>14</td>
<td> </td>
<td>2.84</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>401</td>
<td>16</td>
<td> </td>
<td>2.60</td>
<td> </td>
<td>&lt;0.001</td>
<td>514</td>
<td>15</td>
<td> </td>
<td>2.71</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>5-Aminosalicylic acid</td>
<td>1698</td>
<td> </td>
<td>19</td>
<td>3.23</td>
<td>0.054</td>
<td> </td>
<td>52.3</td>
<td> </td>
<td>47</td>
<td>1.72</td>
<td>0.044</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>1467</td>
<td>14</td>
<td> </td>
<td>3.17</td>
<td> </td>
<td>0.092</td>
<td>29.9</td>
<td>22</td>
<td> </td>
<td>1.48</td>
<td> </td>
<td>0.025</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>2070</td>
<td>16</td>
<td> </td>
<td>3.32</td>
<td> </td>
<td>0.021</td>
<td>78.2</td>
<td>54</td>
<td> </td>
<td>1.89</td>
<td> </td>
<td>0.033</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>1557</td>
<td>12</td>
<td> </td>
<td>3.19</td>
<td> </td>
<td>0.312</td>
<td>48.8</td>
<td>16</td>
<td> </td>
<td>1.69</td>
<td> </td>
<td>0.832</td>
</tr>
<tr class="odd">
<td>Aminopterin</td>
<td>0.007</td>
<td> </td>
<td>54</td>
<td>-2.14</td>
<td>0.036</td>
<td> </td>
<td>682</td>
<td> </td>
<td>27</td>
<td>2.83</td>
<td>0.0250</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>0.005</td>
<td>20</td>
<td> </td>
<td>-2.28</td>
<td> </td>
<td>0.216</td>
<td>889</td>
<td>20</td>
<td> </td>
<td>2.95</td>
<td> </td>
<td>0.017</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>0.012</td>
<td>46</td>
<td> </td>
<td>-1.93</td>
<td> </td>
<td>0.013</td>
<td>545</td>
<td>8</td>
<td> </td>
<td>2.74</td>
<td> </td>
<td>0.041</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>0.005</td>
<td>23</td>
<td> </td>
<td>-2.33</td>
<td> </td>
<td>0.079</td>
<td>611</td>
<td>12</td>
<td> </td>
<td>2.79</td>
<td> </td>
<td>0.345</td>
</tr>
<tr class="odd">
<td>Amitriptyline HCl</td>
<td>7.23</td>
<td> </td>
<td>14</td>
<td>0.86</td>
<td>0.348</td>
<td> </td>
<td>9.76</td>
<td> </td>
<td>19</td>
<td>0.99</td>
<td>0.365</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>6.03</td>
<td>23</td>
<td> </td>
<td>0.78</td>
<td> </td>
<td>0.163</td>
<td>10.8</td>
<td>31</td>
<td> </td>
<td>1.03</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>7.86</td>
<td>28</td>
<td> </td>
<td>0.90</td>
<td> </td>
<td>0.469</td>
<td>7.57</td>
<td>72</td>
<td> </td>
<td>0.88</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>7.81</td>
<td>18</td>
<td> </td>
<td>0.89</td>
<td> </td>
<td>0.445</td>
<td>10.9</td>
<td>10</td>
<td> </td>
<td>1.04</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Arsenic trioxide</td>
<td>2.51</td>
<td> </td>
<td>61</td>
<td>0.40</td>
<td>0.004</td>
<td> </td>
<td>10.4</td>
<td> </td>
<td>91</td>
<td>1.02</td>
<td>&lt;0.001</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>2.41</td>
<td>33</td>
<td> </td>
<td>0.38</td>
<td> </td>
<td>0.527</td>
<td>7.77</td>
<td>33</td>
<td> </td>
<td>0.89</td>
<td> </td>
<td>0.694</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>1.04</td>
<td>7</td>
<td> </td>
<td>0.02</td>
<td> </td>
<td>0.002</td>
<td>2.55</td>
<td>75</td>
<td> </td>
<td>0.41</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>4.09</td>
<td>52</td>
<td> </td>
<td>0.61</td>
<td> </td>
<td>0.006</td>
<td>20.9</td>
<td>31</td>
<td> </td>
<td>1.32</td>
<td> </td>
<td>0.0006</td>
</tr>
<tr class="odd">
<td>Atropine sulfate</td>
<td>85.6</td>
<td> </td>
<td>49</td>
<td>1.93</td>
<td>0.049</td>
<td> </td>
<td>91.9</td>
<td> </td>
<td>13</td>
<td>1.96</td>
<td>0.9881</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>54.1</td>
<td>55</td>
<td> </td>
<td>1.73</td>
<td> </td>
<td>0.046</td>
<td>85.4</td>
<td>12</td>
<td> </td>
<td>1.93</td>
<td> </td>
<td>0.8903</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>133</td>
<td>31</td>
<td> </td>
<td>2.12</td>
<td> </td>
<td>0.024</td>
<td>104</td>
<td>85</td>
<td> </td>
<td>2.02</td>
<td> </td>
<td>0.9069</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>70.0</td>
<td>8</td>
<td> </td>
<td>1.85</td>
<td> </td>
<td>0.641</td>
<td>83.2</td>
<td>25</td>
<td> </td>
<td>1.92</td>
<td> </td>
<td>0.9832</td>
</tr>
<tr class="odd">
<td>Boric acid</td>
<td>2228</td>
<td> </td>
<td>69</td>
<td>3.35</td>
<td>0.010</td>
<td> </td>
<td>473</td>
<td> </td>
<td>8</td>
<td>2.67</td>
<td>0.9306</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>1497</td>
<td>32</td>
<td> </td>
<td>3.18</td>
<td> </td>
<td>0.189</td>
<td>440</td>
<td>31</td>
<td> </td>
<td>2.64</td>
<td> </td>
<td>0.9692</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>3987</td>
<td>17</td>
<td> </td>
<td>3.60</td>
<td> </td>
<td>0.004</td>
<td>517</td>
<td>73</td>
<td> </td>
<td>2.71</td>
<td> </td>
<td>0.7391</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>1202</td>
<td>48</td>
<td> </td>
<td>3.08</td>
<td> </td>
<td>0.021</td>
<td>464</td>
<td>2</td>
<td> </td>
<td>2.67</td>
<td> </td>
<td>0.7680</td>
</tr>
<tr class="odd">
<td>Busulfan</td>
<td>135</td>
<td> </td>
<td>119</td>
<td>2.13</td>
<td>0.002</td>
<td> </td>
<td>278</td>
<td> </td>
<td>11</td>
<td>2.44</td>
<td>0.659</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>40.0</td>
<td>48</td>
<td> </td>
<td>1.60</td>
<td> </td>
<td>0.012</td>
<td>253</td>
<td>27</td>
<td> </td>
<td>2.40</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>321</td>
<td>56</td>
<td> </td>
<td>2.51</td>
<td> </td>
<td>&lt; 0.001</td>
<td>268</td>
<td>72</td>
<td> </td>
<td>2.43</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>43.7</td>
<td>4</td>
<td> </td>
<td>1.64</td>
<td> </td>
<td>0.033</td>
<td>313</td>
<td>12</td>
<td> </td>
<td>2.50</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Cadmium chloride</td>
<td>0.565</td>
<td> </td>
<td>39</td>
<td>-0.25</td>
<td>0.124</td>
<td> </td>
<td>1.98</td>
<td> </td>
<td>10</td>
<td>0.30</td>
<td>0.733</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>0.480</td>
<td>14</td>
<td> </td>
<td>-0.32</td>
<td> </td>
<td>NA</td>
<td>2.20</td>
<td>37</td>
<td> </td>
<td>0.34</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>0.400</td>
<td>32</td>
<td> </td>
<td>-0.40</td>
<td> </td>
<td>NA</td>
<td>1.88</td>
<td>65</td>
<td> </td>
<td>0.27</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>0.817</td>
<td>53</td>
<td> </td>
<td>-0.09</td>
<td> </td>
<td>NA</td>
<td>1.86</td>
<td>8</td>
<td><strong> </strong></td>
<td>0.27</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Caffeine</td>
<td>161</td>
<td> </td>
<td>18</td>
<td>2.21</td>
<td>0.481</td>
<td> </td>
<td>661</td>
<td> </td>
<td>21</td>
<td>2.82</td>
<td>0.296</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>133</td>
<td>10</td>
<td> </td>
<td>2.12</td>
<td> </td>
<td>NA</td>
<td>817</td>
<td>31</td>
<td> </td>
<td>2.91</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>157</td>
<td>52</td>
<td> </td>
<td>2.20</td>
<td> </td>
<td>NA</td>
<td>591</td>
<td>32</td>
<td> </td>
<td>2.77</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>191</td>
<td>7.5</td>
<td> </td>
<td>2.28</td>
<td> </td>
<td>NA</td>
<td>574</td>
<td>1</td>
<td> </td>
<td>2.76</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Carbamazepine</td>
<td>109</td>
<td> </td>
<td>35</td>
<td>2.04</td>
<td>0.049</td>
<td> </td>
<td>128</td>
<td> </td>
<td>85</td>
<td>2.11</td>
<td>0.432</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>83.0</td>
<td>14</td>
<td> </td>
<td>1.92</td>
<td> </td>
<td>NA</td>
<td>66.1</td>
<td>13</td>
<td> </td>
<td>1.82</td>
<td></td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>152</td>
<td>37</td>
<td> </td>
<td>2.18</td>
<td> </td>
<td>NA</td>
<td>253</td>
<td>129</td>
<td> </td>
<td>2.40</td>
<td></td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>91.8</td>
<td>12</td>
<td> </td>
<td>1.96</td>
<td> </td>
<td>NA</td>
<td>63.9</td>
<td>8</td>
<td> </td>
<td>1.81</td>
<td></td>
<td>NA</td>
</tr>
<tr class="odd">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Carbon tetrachloride</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Chloral hydrate</td>
<td>187</td>
<td> </td>
<td>25</td>
<td>2.27</td>
<td>0.004</td>
<td> </td>
<td>137</td>
<td> </td>
<td>17</td>
<td>2.14</td>
<td>0.302</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>151</td>
<td>10</td>
<td> </td>
<td>2.18</td>
<td> </td>
<td>0.008</td>
<td>140</td>
<td>24</td>
<td> </td>
<td>2.15</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>241</td>
<td>10</td>
<td> </td>
<td>2.38</td>
<td> </td>
<td>0.002</td>
<td>159</td>
<td>32</td>
<td> </td>
<td>2.20</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>170</td>
<td>12</td>
<td> </td>
<td>2.23</td>
<td> </td>
<td>0.181</td>
<td>112</td>
<td>2</td>
<td> </td>
<td>2.05</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Chloramphenicol</td>
<td>161</td>
<td> </td>
<td>67</td>
<td>2.21</td>
<td>&lt;0.001</td>
<td> </td>
<td>366</td>
<td> </td>
<td>13</td>
<td>2.56</td>
<td>0.750</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>55.3</td>
<td>22</td>
<td> </td>
<td> 1.74</td>
<td> </td>
<td>&lt;0.001</td>
<td>318</td>
<td>45</td>
<td> </td>
<td>2.50</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>273</td>
<td>30</td>
<td> </td>
<td> 2.44</td>
<td> </td>
<td>0.001</td>
<td>414</td>
<td>44</td>
<td> </td>
<td>2.62</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>156</td>
<td>18</td>
<td> </td>
<td> 2.19</td>
<td> </td>
<td>0.165</td>
<td>367</td>
<td>22</td>
<td> </td>
<td>2.56</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Citric acid</td>
<td>829</td>
<td> </td>
<td>41</td>
<td>2.92</td>
<td>0.002</td>
<td> </td>
<td>424</td>
<td> </td>
<td>25</td>
<td>2.63</td>
<td>0.006</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>473</td>
<td>29</td>
<td> </td>
<td>2.68</td>
<td> </td>
<td>0.001</td>
<td>526</td>
<td>16</td>
<td> </td>
<td>2.72</td>
<td> </td>
<td>0.009</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>1148</td>
<td>13</td>
<td> </td>
<td>3.06</td>
<td></td>
<td>0.003</td>
<td>312</td>
<td>17</td>
<td> </td>
<td>2.49</td>
<td> </td>
<td>0.002</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>865</td>
<td>19</td>
<td> </td>
<td>2.94</td>
<td> </td>
<td>0.298</td>
<td>433</td>
<td>5</td>
<td> </td>
<td>2.64</td>
<td> </td>
<td>0.483</td>
</tr>
<tr class="even">
<td>Colchicine</td>
<td>0.047</td>
<td> </td>
<td>85</td>
<td>-1.33</td>
<td>0.001</td>
<td> </td>
<td>0.007</td>
<td> </td>
<td>22</td>
<td>-2.16</td>
<td>0.174</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.020</td>
<td>11</td>
<td> </td>
<td> -1.70</td>
<td> </td>
<td>0.0028</td>
<td>0.005</td>
<td>46</td>
<td> </td>
<td>-2.28</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>0.093</td>
<td>45</td>
<td> </td>
<td> -1.03</td>
<td> </td>
<td>0.0005</td>
<td>0.008</td>
<td>10</td>
<td> </td>
<td>-2.12</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.028</td>
<td>1</td>
<td> </td>
<td> -1.55</td>
<td> </td>
<td>0.0914</td>
<td>0.008</td>
<td>21</td>
<td> </td>
<td>-2.09</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Cupric sulfate pentahydrate</td>
<td>70.6</td>
<td></td>
<td>85</td>
<td>1.85</td>
<td>&lt;0.001</td>
<td></td>
<td>197</td>
<td></td>
<td>4</td>
<td>2.29</td>
<td>0.374</td>
<td></td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>82.7</td>
<td>4</td>
<td> </td>
<td>1.92</td>
<td></td>
<td>0.001</td>
<td>190</td>
<td>10</td>
<td> </td>
<td>2.28</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>123</td>
<td>44</td>
<td> </td>
<td>2.09</td>
<td> </td>
<td>&lt;0.001</td>
<td>195</td>
<td>6</td>
<td> </td>
<td>2.29</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>5.70</td>
<td>31</td>
<td> </td>
<td>0.76</td>
<td> </td>
<td>&lt;0.001</td>
<td>207</td>
<td>3</td>
<td> </td>
<td>2.32</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Cycloheximide</td>
<td>0.293</td>
<td> </td>
<td>104</td>
<td>-0.53</td>
<td>0.021</td>
<td> </td>
<td>0.082</td>
<td> </td>
<td>43</td>
<td>-1.09</td>
<td>0.302</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.125</td>
<td>45</td>
<td> </td>
<td>-0.90</td>
<td> </td>
<td>0.118</td>
<td>0.053</td>
<td>22</td>
<td> </td>
<td>-1.28</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>0.647</td>
<td>70</td>
<td> </td>
<td>-0.19</td>
<td> </td>
<td>0.007</td>
<td>0.120</td>
<td>78</td>
<td> </td>
<td>-0.92</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.109</td>
<td>23</td>
<td> </td>
<td>-0.96</td>
<td> </td>
<td>0.076</td>
<td>0.071</td>
<td>19</td>
<td> </td>
<td>-1.15</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Dibutyl phthalate</td>
<td>78.3</td>
<td> </td>
<td>124</td>
<td>1.89</td>
<td>&lt; 0.001</td>
<td> </td>
<td>32.6</td>
<td> </td>
<td>41</td>
<td>1.51</td>
<td>0.408</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>23.5</td>
<td>17</td>
<td> </td>
<td>1.37</td>
<td> </td>
<td>0.012</td>
<td>28.3</td>
<td>27</td>
<td> </td>
<td>1.45</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>191</td>
<td>50</td>
<td> </td>
<td>2.28</td>
<td> </td>
<td>&lt;0.001</td>
<td>47.4</td>
<td>73</td>
<td> </td>
<td>1.68</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>20.7</td>
<td>7</td>
<td> </td>
<td>1.32</td>
<td></td>
<td>0.005</td>
<td>22.0</td>
<td>6</td>
<td> </td>
<td>1.34</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Dichlorvos</td>
<td>20.3</td>
<td> </td>
<td>57</td>
<td>1.31</td>
<td>0.002</td>
<td> </td>
<td>11.1</td>
<td> </td>
<td>20</td>
<td>1.05</td>
<td>0.181</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>9.80</td>
<td>35</td>
<td> </td>
<td>0.99</td>
<td> </td>
<td>0.001</td>
<td>8.56</td>
<td>27</td>
<td> </td>
<td>0.93</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>32.8</td>
<td>6</td>
<td> </td>
<td>1.52</td>
<td> </td>
<td>0.002</td>
<td>12.4</td>
<td>30</td>
<td> </td>
<td>1.09</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>18.3</td>
<td>11</td>
<td> </td>
<td>1.26</td>
<td> </td>
<td>0.823</td>
<td>12.2</td>
<td>3</td>
<td> </td>
<td>1.09</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Diethyl phthalate</td>
<td>113</td>
<td> </td>
<td>28</td>
<td>2.05</td>
<td>0.127</td>
<td> </td>
<td>145</td>
<td> </td>
<td>44</td>
<td>2.16</td>
<td>0.049</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>85.5</td>
<td>34</td>
<td> </td>
<td>1.93</td>
<td> </td>
<td>0.092</td>
<td>174</td>
<td>8</td>
<td> </td>
<td>2.24</td>
<td> </td>
<td>0.196</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>147</td>
<td>26</td>
<td> </td>
<td>2.17</td>
<td> </td>
<td>0.070</td>
<td>71.5</td>
<td>94</td>
<td> </td>
<td>1.85</td>
<td> </td>
<td>0.018</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>106</td>
<td>24</td>
<td> </td>
<td>2.03</td>
<td> </td>
<td>0.846</td>
<td>189</td>
<td>18</td>
<td> </td>
<td>2.28</td>
<td> </td>
<td>0.127</td>
</tr>
<tr class="even">
<td>Digoxin</td>
<td>520</td>
<td> </td>
<td>62</td>
<td>2.72</td>
<td>0.043</td>
<td> </td>
<td>0.00314</td>
<td> </td>
<td>88</td>
<td>-2.50</td>
<td>&lt;0.001</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>351</td>
<td>39</td>
<td> </td>
<td>2.54</td>
<td> </td>
<td>0.167</td>
<td>0.00538</td>
<td>13</td>
<td> </td>
<td>-2.27</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>892</td>
<td>36</td>
<td> </td>
<td>2.95</td>
<td> </td>
<td>0.017</td>
<td>0.00005</td>
<td>36</td>
<td> </td>
<td>-4.29</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>317</td>
<td>21</td>
<td> </td>
<td>2.50</td>
<td> </td>
<td>0.144</td>
<td>0.00398</td>
<td>7</td>
<td> </td>
<td>-2.40</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="even">
<td>Dimethylformamide</td>
<td>5242</td>
<td> </td>
<td>6</td>
<td>3.72</td>
<td>0.296</td>
<td> </td>
<td>7856</td>
<td> </td>
<td>19</td>
<td>3.90</td>
<td>&lt;0.001</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>5343</td>
<td>10</td>
<td> </td>
<td>3.73</td>
<td> </td>
<td>NA</td>
<td>9353</td>
<td>2</td>
<td> </td>
<td>3.97</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>5483</td>
<td>9</td>
<td> </td>
<td>3.74</td>
<td> </td>
<td>NA</td>
<td>7817</td>
<td>1</td>
<td> </td>
<td>3.89</td>
<td> </td>
<td>0.508</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>4900</td>
<td>4</td>
<td> </td>
<td>3.69</td>
<td> </td>
<td>NA</td>
<td>6397</td>
<td>3</td>
<td> </td>
<td>3.81</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="even">
<td>Diquat dibromide monohydrate</td>
<td>15.1</td>
<td></td>
<td>120</td>
<td>1.18</td>
<td>0.017</td>
<td></td>
<td>4.73</td>
<td></td>
<td>37</td>
<td>0.67</td>
<td>0.217</td>
<td></td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>3.90</td>
<td>23</td>
<td> </td>
<td>0.59</td>
<td> </td>
<td>0.040</td>
<td>3.59</td>
<td>23</td>
<td> </td>
<td>0.56</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>36.1</td>
<td>98</td>
<td> </td>
<td>1.56</td>
<td> </td>
<td>0.006</td>
<td>6.77</td>
<td>55</td>
<td> </td>
<td>0.83</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>5.40</td>
<td>25</td>
<td> </td>
<td>0.73</td>
<td> </td>
<td>0.190</td>
<td>3.84</td>
<td>8</td>
<td> </td>
<td>0.58</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Disulfoton</td>
<td>98.6</td>
<td> </td>
<td>55</td>
<td>1.99</td>
<td>0.003</td>
<td> </td>
<td>378</td>
<td> </td>
<td>99</td>
<td>2.58</td>
<td>&lt;0.001</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>137</td>
<td>55</td>
<td></td>
<td>2.14</td>
<td> </td>
<td>NA</td>
<td>140</td>
<td>19</td>
<td> </td>
<td>2.15</td>
<td> </td>
<td>0.002</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>808</td>
<td>26</td>
<td> </td>
<td>2.91</td>
<td> </td>
<td>&lt;0.001</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>60.4</td>
<td>87</td>
<td> </td>
<td>1.78</td>
<td> </td>
<td>NA</td>
<td>186</td>
<td>32</td>
<td> </td>
<td>2.27</td>
<td> </td>
<td>0.018</td>
</tr>
<tr class="even">
<td>Endosulfan</td>
<td>8.02</td>
<td> </td>
<td>78</td>
<td>0.90</td>
<td>0.046</td>
<td> </td>
<td>2.35</td>
<td> </td>
<td>43</td>
<td>0.37</td>
<td>0.029</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>5.30</td>
<td>57</td>
<td> </td>
<td>0.72</td>
<td> </td>
<td>0.447</td>
<td>3.44</td>
<td>17</td>
<td> </td>
<td>0.54</td>
<td> </td>
<td>0.020</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>15.2</td>
<td>78</td>
<td> </td>
<td>1.18</td>
<td> </td>
<td>0.018</td>
<td>1.42</td>
<td>50</td>
<td> </td>
<td>0.15</td>
<td> </td>
<td>0.018</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>3.60</td>
<td>42</td>
<td> </td>
<td>0.56</td>
<td> </td>
<td>0.080</td>
<td>2.19</td>
<td>20</td>
<td> </td>
<td>0.34</td>
<td> </td>
<td>0.927</td>
</tr>
<tr class="even">
<td>Epinephrine bitartrate</td>
<td>59.4</td>
<td> </td>
<td>12</td>
<td>1.77</td>
<td>0.048</td>
<td> </td>
<td>90.6</td>
<td> </td>
<td>24</td>
<td>1.96</td>
<td>0.119</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>51.5</td>
<td>12</td>
<td> </td>
<td>1.71</td>
<td> </td>
<td>0.018</td>
<td>115</td>
<td>9</td>
<td> </td>
<td>2.06</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>63.4</td>
<td>11</td>
<td> </td>
<td>1.80</td>
<td> </td>
<td>0.165</td>
<td>81.7</td>
<td>35</td>
<td> </td>
<td>1.91</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>63.4</td>
<td>3</td>
<td> </td>
<td>1.80</td>
<td> </td>
<td>0.149</td>
<td>75.0</td>
<td>16</td>
<td> </td>
<td>1.88</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Ethanol</td>
<td>6731</td>
<td> </td>
<td>23</td>
<td>3.83</td>
<td>0.075</td>
<td> </td>
<td>10184</td>
<td> </td>
<td>18</td>
<td>4.01</td>
<td>0.035</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>5360</td>
<td>33</td>
<td> </td>
<td>3.73</td>
<td> </td>
<td>NA</td>
<td>8290</td>
<td>5</td>
<td> </td>
<td>3.92</td>
<td> </td>
<td>0.019</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>8420</td>
<td>14</td>
<td> </td>
<td>3.93</td>
<td> </td>
<td>NA</td>
<td>12013</td>
<td>19</td>
<td> </td>
<td>4.08</td>
<td> </td>
<td>0.029</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>6413</td>
<td>5</td>
<td> </td>
<td>3.81</td>
<td> </td>
<td>NA</td>
<td>10250</td>
<td>9</td>
<td> </td>
<td>4.01</td>
<td> </td>
<td>0.752</td>
</tr>
<tr class="even">
<td>Ethylene glycol</td>
<td>25292</td>
<td> </td>
<td>26</td>
<td>4.40</td>
<td>0.007</td>
<td> </td>
<td>42600</td>
<td> </td>
<td>15</td>
<td>4.63</td>
<td>0.063</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>18325</td>
<td>9</td>
<td> </td>
<td> 4.26</td>
<td> </td>
<td>0.004</td>
<td>38000</td>
<td>12</td>
<td> </td>
<td>4.58</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>31650</td>
<td>24</td>
<td> </td>
<td> 4.50</td>
<td> </td>
<td>0.010</td>
<td>49800</td>
<td>9</td>
<td> </td>
<td>4.70</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>25900</td>
<td>12</td>
<td> </td>
<td> 4.41</td>
<td> </td>
<td>0.505</td>
<td>40000</td>
<td>13</td>
<td> </td>
<td>4.60</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Fenpropathrin</td>
<td>27.2</td>
<td> </td>
<td>49</td>
<td>1.43</td>
<td>0.301</td>
<td> </td>
<td>2.60</td>
<td> </td>
<td>39</td>
<td>0.41</td>
<td>0.031</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>22.6</td>
<td>11</td>
<td> </td>
<td>1.35</td>
<td> </td>
<td>NA</td>
<td>3.73</td>
<td>27</td>
<td> </td>
<td>0.57</td>
<td> </td>
<td>0.013</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>42.4</td>
<td>63</td>
<td> </td>
<td>1.63</td>
<td> </td>
<td>NA</td>
<td>2.23</td>
<td>28</td>
<td> </td>
<td>0.35</td>
<td> </td>
<td>0.375</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>16.7</td>
<td>12</td>
<td> </td>
<td>1.22</td>
<td> </td>
<td>NA</td>
<td>1.82</td>
<td>17</td>
<td> </td>
<td>0.26</td>
<td> </td>
<td>0.044</td>
</tr>
<tr class="even">
<td>Gibberellic Acid</td>
<td>7842</td>
<td> </td>
<td>3</td>
<td>3.89</td>
<td>0.621</td>
<td> </td>
<td>2866</td>
<td> </td>
<td>2</td>
<td>3.46</td>
<td>0.862</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>8027</td>
<td>11</td>
<td> </td>
<td>3.90</td>
<td> </td>
<td>NA</td>
<td>2850</td>
<td>14</td>
<td> </td>
<td>3.45</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>2940</td>
<td>9</td>
<td> </td>
<td>3.47</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>7657</td>
<td>10</td>
<td> </td>
<td>3.88</td>
<td> </td>
<td>NA</td>
<td>2807</td>
<td>4</td>
<td> </td>
<td>3.45</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Glutethimide</td>
<td>192</td>
<td> </td>
<td>43</td>
<td>2.28</td>
<td>&lt; 0.001</td>
<td> </td>
<td>177</td>
<td> </td>
<td>5</td>
<td>2.25</td>
<td>0.968</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>167</td>
<td>4</td>
<td> </td>
<td>2.22</td>
<td> </td>
<td>0.029</td>
<td>187</td>
<td>34</td>
<td> </td>
<td>2.27</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>284.3</td>
<td>7</td>
<td> </td>
<td>2.45</td>
<td> </td>
<td>&lt;0.001</td>
<td>170</td>
<td>14</td>
<td> </td>
<td>2.23</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>125.3</td>
<td>7</td>
<td> </td>
<td>2.10</td>
<td> </td>
<td>&lt;0.001</td>
<td>176</td>
<td>16</td>
<td> </td>
<td>2.24</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Glycerol</td>
<td>28904</td>
<td> </td>
<td>33</td>
<td>4.46</td>
<td>0.846</td>
<td> </td>
<td>27108</td>
<td> </td>
<td>31</td>
<td>4.43</td>
<td>0.200</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>20000</td>
<td>15</td>
<td> </td>
<td>4.30</td>
<td> </td>
<td>NA</td>
<td>34267</td>
<td>45</td>
<td> </td>
<td>4.53</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>38878</td>
<td>73</td>
<td> </td>
<td>4.59</td>
<td> </td>
<td>NA</td>
<td>18023</td>
<td>46</td>
<td> </td>
<td>4.26</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>27833</td>
<td>39</td>
<td> </td>
<td>4.44</td>
<td> </td>
<td>NA</td>
<td>29033</td>
<td>16</td>
<td> </td>
<td>4.46</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Haloperidol</td>
<td>6.26</td>
<td> </td>
<td>24</td>
<td>0.80</td>
<td>0.006</td>
<td> </td>
<td>3.57</td>
<td> </td>
<td>7</td>
<td>0.55</td>
<td>0.935</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>5.30</td>
<td>12</td>
<td> </td>
<td>0.72</td>
<td> </td>
<td>0.030</td>
<td>3.69</td>
<td>27</td>
<td> </td>
<td>0.57</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>8.00</td>
<td>8</td>
<td> </td>
<td>0.90</td>
<td> </td>
<td>0.002</td>
<td>3.72</td>
<td>49</td>
<td> </td>
<td>0.57</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>5.50</td>
<td>12</td>
<td> </td>
<td>0.74</td>
<td> </td>
<td>0.061</td>
<td>3.29</td>
<td>35</td>
<td> </td>
<td>0.52</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Hexachlorophene</td>
<td>4.48</td>
<td> </td>
<td>27</td>
<td>0.65</td>
<td>0.174</td>
<td> </td>
<td>0.031</td>
<td> </td>
<td>41</td>
<td>-1.50</td>
<td>0.097</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>5.00</td>
<td>48</td>
<td> </td>
<td>0.70</td>
<td> </td>
<td>NA</td>
<td>0.027</td>
<td>16</td>
<td> </td>
<td>-1.57</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>5.30</td>
<td>33</td>
<td> </td>
<td>0.72</td>
<td> </td>
<td>NA</td>
<td>0.046</td>
<td>44</td>
<td> </td>
<td>-1.34</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>3.10</td>
<td>9</td>
<td> </td>
<td>0.49</td>
<td> </td>
<td>NA</td>
<td>0.021</td>
<td>11</td>
<td> </td>
<td>-1.67</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Lactic acid</td>
<td>3073</td>
<td> </td>
<td>12</td>
<td>3.49</td>
<td>0.160</td>
<td> </td>
<td>1308</td>
<td> </td>
<td>1</td>
<td>3.12</td>
<td>0.904</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>2943</td>
<td>11</td>
<td> </td>
<td>3.47</td>
<td> </td>
<td>NA</td>
<td>1290</td>
<td>4</td>
<td> </td>
<td>3.11</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>3487</td>
<td>16</td>
<td> </td>
<td>3.54</td>
<td> </td>
<td>NA</td>
<td>1320</td>
<td>5</td>
<td> </td>
<td>3.12</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>2790</td>
<td>9</td>
<td> </td>
<td>3.45</td>
<td> </td>
<td>NA</td>
<td>1313</td>
<td>11</td>
<td> </td>
<td>3.12</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Lindane</td>
<td>161</td>
<td> </td>
<td>58</td>
<td>2.21</td>
<td>0.066</td>
<td> </td>
<td>19.3</td>
<td> </td>
<td>20</td>
<td>1.29</td>
<td>0.203</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>125</td>
<td>95</td>
<td> </td>
<td>2.10</td>
<td> </td>
<td>NA</td>
<td>19.1</td>
<td>17</td>
<td> </td>
<td>1.28</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>266</td>
<td>36</td>
<td> </td>
<td>2.43</td>
<td> </td>
<td>NA</td>
<td>23.2</td>
<td>31</td>
<td> </td>
<td>1.37</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>90.4</td>
<td>122</td>
<td> </td>
<td>1.96</td>
<td> </td>
<td>NA</td>
<td>15.6</td>
<td>15</td>
<td> </td>
<td>1.19</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Lithium carbonate</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>477</td>
<td> </td>
<td>13</td>
<td>2.68</td>
<td>0.295</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>564</td>
<td>12</td>
<td> </td>
<td>2.75</td>
<td> </td>
<td>NA</td>
<td>411</td>
<td>29</td>
<td> </td>
<td>2.61</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>486</td>
<td>20</td>
<td> </td>
<td>2.69</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>535</td>
<td>6</td>
<td> </td>
<td>2.73</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Meprobamate</td>
<td>539</td>
<td> </td>
<td>54</td>
<td>2.73</td>
<td>&lt;0.001</td>
<td> </td>
<td>516</td>
<td> </td>
<td>61</td>
<td>2.71</td>
<td>0.027</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>353</td>
<td>14</td>
<td> </td>
<td>2.55</td>
<td> </td>
<td>0.001</td>
<td>761</td>
<td>15</td>
<td> </td>
<td>2.88</td>
<td> </td>
<td>0.0758</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>877</td>
<td>15</td>
<td> </td>
<td>2.94</td>
<td> </td>
<td>&lt;0.001</td>
<td>163</td>
<td>116</td>
<td> </td>
<td>2.21</td>
<td> </td>
<td>0.0098</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>386</td>
<td>2</td>
<td> </td>
<td>2.59</td>
<td> </td>
<td>0.005</td>
<td>624</td>
<td>14</td>
<td> </td>
<td>2.80</td>
<td> </td>
<td>0.1648</td>
</tr>
<tr class="odd">
<td>Mercury chloride</td>
<td>4.32</td>
<td> </td>
<td>33</td>
<td>0.64</td>
<td>0.021</td>
<td> </td>
<td>5.87</td>
<td> </td>
<td>15</td>
<td>0.77</td>
<td>0.120</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>3.50</td>
<td>5</td>
<td> </td>
<td>0.54</td>
<td> </td>
<td>0.083</td>
<td>6.87</td>
<td>15</td>
<td> </td>
<td>0.84</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>6.00</td>
<td>31</td>
<td> </td>
<td>0.78</td>
<td> </td>
<td>0.008</td>
<td>5.40</td>
<td>19</td>
<td> </td>
<td>0.73</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>3.50</td>
<td>3</td>
<td> </td>
<td>0.54</td>
<td> </td>
<td>0.110</td>
<td>5.35</td>
<td>2</td>
<td> </td>
<td>0.73</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Methanol</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>1616</td>
<td> </td>
<td>42</td>
<td>3.21</td>
<td>0.007</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>NA</td>
<td> </td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>1133</td>
<td>19</td>
<td> </td>
<td>3.05</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>NA</td>
<td> </td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>2100</td>
<td>11</td>
<td> </td>
<td>3.32</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Nicotine</td>
<td>378</td>
<td> </td>
<td>25</td>
<td>2.58</td>
<td>0.128</td>
<td> </td>
<td>113</td>
<td> </td>
<td>17</td>
<td>2.05</td>
<td>0.700</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>272</td>
<td>24</td>
<td> </td>
<td>2.43</td>
<td> </td>
<td>NA</td>
<td>94.3</td>
<td>26</td>
<td> </td>
<td>1.97</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>412</td>
<td>33</td>
<td> </td>
<td>2.61</td>
<td> </td>
<td>NA</td>
<td>134</td>
<td>59</td>
<td> </td>
<td>2.13</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>450</td>
<td>12</td>
<td> </td>
<td>2.65</td>
<td> </td>
<td>NA</td>
<td>112</td>
<td>25</td>
<td> </td>
<td>2.05</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Paraquat</td>
<td>23.3</td>
<td> </td>
<td>8</td>
<td>1.37</td>
<td>1.000</td>
<td> </td>
<td>66.1</td>
<td> </td>
<td>40</td>
<td>1.82</td>
<td>0.047</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>21.3</td>
<td>34</td>
<td> </td>
<td>1.33</td>
<td> </td>
<td>NA</td>
<td>48.3</td>
<td>13</td>
<td> </td>
<td>1.68</td>
<td> </td>
<td>0.089</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>24.9</td>
<td>67</td>
<td> </td>
<td>1.40</td>
<td> </td>
<td>NA</td>
<td>96.6</td>
<td>39</td>
<td> </td>
<td>1.98</td>
<td> </td>
<td>0.018</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>23.7</td>
<td>64</td>
<td> </td>
<td>1.37</td>
<td> </td>
<td>NA</td>
<td>53.4</td>
<td>10</td>
<td> </td>
<td>1.73</td>
<td> </td>
<td>0.279</td>
</tr>
<tr class="odd">
<td>Parathion</td>
<td>61.8</td>
<td> </td>
<td>111</td>
<td>1.79</td>
<td>0.014</td>
<td> </td>
<td>31.4</td>
<td> </td>
<td>8</td>
<td>1.50</td>
<td>0.845</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>22.7</td>
<td>53</td>
<td> </td>
<td>1.36</td>
<td> </td>
<td>0.064</td>
<td>34.0</td>
<td>30</td>
<td> </td>
<td>1.53</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>141</td>
<td>70</td>
<td> </td>
<td>2.15</td>
<td> </td>
<td>0.005</td>
<td>31.2</td>
<td>38</td>
<td> </td>
<td>1.49</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>22</td>
<td>22</td>
<td> </td>
<td>1.34</td>
<td> </td>
<td>0.081</td>
<td>29.0</td>
<td>29</td>
<td> </td>
<td>1.46</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Phenobarbital</td>
<td>612</td>
<td> </td>
<td>21</td>
<td>2.79</td>
<td>0.232</td>
<td> </td>
<td>478</td>
<td> </td>
<td>39</td>
<td>2.68</td>
<td>0.027</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>634</td>
<td>21</td>
<td> </td>
<td>2.80</td>
<td> </td>
<td>NA</td>
<td>693</td>
<td>26</td>
<td> </td>
<td>2.84</td>
<td> </td>
<td>0.010</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>726</td>
<td>35</td>
<td> </td>
<td>2.86</td>
<td> </td>
<td>NA</td>
<td>360</td>
<td>27</td>
<td> </td>
<td>2.56</td>
<td> </td>
<td>0.072</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>476</td>
<td>23</td>
<td> </td>
<td>2.68</td>
<td> </td>
<td>NA</td>
<td>381</td>
<td>18</td>
<td> </td>
<td>2.58</td>
<td> </td>
<td>0.173</td>
</tr>
<tr class="odd">
<td>Phenol</td>
<td>70.9</td>
<td> </td>
<td>41</td>
<td> </td>
<td>0.011</td>
<td> </td>
<td>77.7</td>
<td> </td>
<td>22</td>
<td>1.89</td>
<td>0.094</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>50.2</td>
<td>22</td>
<td> </td>
<td>1.70</td>
<td> </td>
<td>0.022</td>
<td>59.1</td>
<td>36</td>
<td> </td>
<td>1.77</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>104</td>
<td>24</td>
<td> </td>
<td>2.02</td>
<td> </td>
<td>0.004</td>
<td>93.2</td>
<td>6</td>
<td> </td>
<td>1.97</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>58.1</td>
<td>12</td>
<td> </td>
<td>1.76</td>
<td> </td>
<td>0.206</td>
<td>80.8</td>
<td>6</td>
<td> </td>
<td>1.91</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Phenylthiourea</td>
<td>119</td>
<td> </td>
<td>90</td>
<td>2.08</td>
<td>0.007</td>
<td> </td>
<td>346</td>
<td> </td>
<td>19</td>
<td>2.54</td>
<td>0.133</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>30.1</td>
<td>66</td>
<td> </td>
<td>1.48</td>
<td> </td>
<td>0.004</td>
<td>363</td>
<td>16</td>
<td> </td>
<td>2.56</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>239</td>
<td>28</td>
<td> </td>
<td>2.38</td>
<td></td>
<td>0.006</td>
<td>401</td>
<td>21</td>
<td> </td>
<td>2.60</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>89</td>
<td>25</td>
<td> </td>
<td>1.95</td>
<td> </td>
<td>0.718</td>
<td>272</td>
<td>26</td>
<td> </td>
<td>2.44</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Physostigmine</td>
<td>28.8</td>
<td> </td>
<td>30</td>
<td>1.46</td>
<td>0.149</td>
<td> </td>
<td>172</td>
<td> </td>
<td>22</td>
<td>2.24</td>
<td>0.623</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>28.2</td>
<td>53</td>
<td> </td>
<td>1.45</td>
<td> </td>
<td>NA</td>
<td>164</td>
<td>3</td>
<td> </td>
<td>2.21</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>37.8</td>
<td>5</td>
<td> </td>
<td>1.58</td>
<td> </td>
<td>NA</td>
<td>213</td>
<td>112</td>
<td> </td>
<td>2.33</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>20.4</td>
<td>33</td>
<td> </td>
<td>1.31</td>
<td> </td>
<td>NA</td>
<td>139</td>
<td>6</td>
<td> </td>
<td>2.14</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Potassium chloride</td>
<td>3635</td>
<td> </td>
<td>7</td>
<td>3.56</td>
<td>0.846</td>
<td> </td>
<td>2279</td>
<td> </td>
<td>13</td>
<td>3.36</td>
<td>0.396</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>3352</td>
<td>14</td>
<td> </td>
<td>3.53</td>
<td> </td>
<td>NA</td>
<td>2560</td>
<td>17</td>
<td> </td>
<td>3.41</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>3842</td>
<td>31</td>
<td> </td>
<td>3.58</td>
<td> </td>
<td>NA</td>
<td>2287</td>
<td>28</td>
<td> </td>
<td>3.36</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>3710</td>
<td>11</td>
<td> </td>
<td>3.57</td>
<td> </td>
<td>NA</td>
<td>1990</td>
<td>8</td>
<td> </td>
<td>3.30</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>Potassium cyanide</td>
<td>64.3</td>
<td> </td>
<td>127</td>
<td>1.81</td>
<td>&lt;0.001</td>
<td> </td>
<td>45.1</td>
<td> </td>
<td>86</td>
<td>1.65</td>
<td>0.340</td>
<td> </td>
</tr>
<tr class="even">
<td>ECBC</td>
<td>15.3</td>
<td>25</td>
<td> </td>
<td>1.18</td>
<td> </td>
<td>0.001</td>
<td>29.3</td>
<td>24</td>
<td> </td>
<td>1.47</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>FAL</td>
<td>159</td>
<td>52</td>
<td> </td>
<td>2.20</td>
<td> </td>
<td>&lt;0.001</td>
<td>89.0</td>
<td>112</td>
<td> </td>
<td>1.95</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>IIVS</td>
<td>18.9</td>
<td>5</td>
<td> </td>
<td>1.28</td>
<td> </td>
<td>0.006</td>
<td>16.9</td>
<td>13</td>
<td> </td>
<td>1.23</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Procainamide HCl</td>
<td>443</td>
<td> </td>
<td>11</td>
<td>2.65</td>
<td>0.007</td>
<td> </td>
<td>1764</td>
<td> </td>
<td>16</td>
<td>3.25</td>
<td>0.053</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>400</td>
<td>4</td>
<td> </td>
<td>2.60</td>
<td> </td>
<td>0.008</td>
<td>1480</td>
<td>14</td>
<td> </td>
<td>3.17</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>431</td>
<td>1</td>
<td> </td>
<td>2.63</td>
<td> </td>
<td>0.396</td>
<td>1787</td>
<td>12</td>
<td> </td>
<td>3.25</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>497</td>
<td>8</td>
<td> </td>
<td>2.70</td>
<td></td>
<td>0.003</td>
<td>2027</td>
<td>11</td>
<td> </td>
<td>3.31</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>2-Propanol</td>
<td>3563</td>
<td> </td>
<td>23</td>
<td>3.55</td>
<td>0.001</td>
<td></td>
<td>5541</td>
<td> </td>
<td>26</td>
<td>3.74</td>
<td>0.033</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>2610</td>
<td>9</td>
<td> </td>
<td>3.42</td>
<td> </td>
<td>&lt; 0.001</td>
<td>5263</td>
<td>11</td>
<td></td>
<td>3.72</td>
<td> </td>
<td>0.797</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>3970</td>
<td>4</td>
<td> </td>
<td>3.60</td>
<td> </td>
<td>0.004</td>
<td>4273</td>
<td>27</td>
<td> </td>
<td>3.63</td>
<td> </td>
<td>0.026</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>4110</td>
<td>4</td>
<td> </td>
<td>3.61</td>
<td> </td>
<td>0.002</td>
<td>7087</td>
<td>7</td>
<td> </td>
<td>3.85</td>
<td> </td>
<td>0.018</td>
</tr>
<tr class="even">
<td>Propranolol HCl</td>
<td>14.9</td>
<td> </td>
<td>16</td>
<td>1.17</td>
<td>0.488</td>
<td> </td>
<td>36.9</td>
<td> </td>
<td>21</td>
<td>1.57</td>
<td>0.003</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>13.6</td>
<td>32</td>
<td> </td>
<td>1.13</td>
<td> </td>
<td>NA</td>
<td>38.27</td>
<td>12</td>
<td> </td>
<td>1.58</td>
<td> </td>
<td>0.325</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>13.5</td>
<td>51</td>
<td> </td>
<td>1.13</td>
<td> </td>
<td>NA</td>
<td>43.8</td>
<td>6</td>
<td> </td>
<td>1.64</td>
<td> </td>
<td>0.006</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>17.6</td>
<td>21</td>
<td> </td>
<td>1.25</td>
<td> </td>
<td>NA</td>
<td>28.6</td>
<td>11</td>
<td> </td>
<td>1.46</td>
<td> </td>
<td>0.001</td>
</tr>
<tr class="even">
<td>Propylparaben</td>
<td>29.9</td>
<td> </td>
<td>64</td>
<td>1.48</td>
<td>0.001</td>
<td> </td>
<td>16.8</td>
<td> </td>
<td>16</td>
<td>1.23</td>
<td>0.066</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>20.9</td>
<td>16</td>
<td> </td>
<td>1.32</td>
<td> </td>
<td>0.045</td>
<td>18.1</td>
<td>13</td>
<td> </td>
<td>1.26</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>51.8</td>
<td>29</td>
<td> </td>
<td>1.71</td>
<td> </td>
<td>&lt; 0.001</td>
<td>18.6</td>
<td>15</td>
<td> </td>
<td>1.27</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>17.1</td>
<td>12</td>
<td> </td>
<td>1.23</td>
<td> </td>
<td>0.003</td>
<td>13.8</td>
<td>9</td>
<td> </td>
<td>1.14</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium arsenite</td>
<td>0.873</td>
<td> </td>
<td>55</td>
<td>-0.06</td>
<td>0.028</td>
<td> </td>
<td>0.532</td>
<td> </td>
<td>44</td>
<td>-0.27</td>
<td>0.061</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.500</td>
<td>6</td>
<td> </td>
<td>-0.30</td>
<td> </td>
<td>0.032</td>
<td>0.790</td>
<td>32</td>
<td> </td>
<td>-0.10</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>1.40</td>
<td>57</td>
<td> </td>
<td>0.15</td>
<td> </td>
<td>0.012</td>
<td>0.336</td>
<td>56</td>
<td> </td>
<td>-0.47</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.700</td>
<td>17</td>
<td> </td>
<td>-0.15</td>
<td> </td>
<td>0.478</td>
<td>0.470</td>
<td>14</td>
<td> </td>
<td>-0.33</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium chloride</td>
<td>4764</td>
<td> </td>
<td>3</td>
<td>3.68</td>
<td>0.759</td>
<td> </td>
<td>2724</td>
<td> </td>
<td>51</td>
<td>3.44</td>
<td>0.045</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>4790</td>
<td>5</td>
<td> </td>
<td>3.68</td>
<td> </td>
<td>NA</td>
<td>3583</td>
<td>7</td>
<td> </td>
<td>3.55</td>
<td> </td>
<td>0.141</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>4625</td>
<td>13</td>
<td> </td>
<td>3.67</td>
<td> </td>
<td>NA</td>
<td>1118</td>
<td>124</td>
<td> </td>
<td>3.05</td>
<td> </td>
<td>0.017</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>4877</td>
<td>9</td>
<td> </td>
<td>3.69</td>
<td> </td>
<td>NA</td>
<td>3470</td>
<td>9</td>
<td> </td>
<td>3.54</td>
<td> </td>
<td>0.161</td>
</tr>
<tr class="even">
<td>Sodium dichromate dihydrate</td>
<td>0.602</td>
<td></td>
<td>9</td>
<td>-0.22</td>
<td>0.822</td>
<td></td>
<td>0.737</td>
<td></td>
<td>19</td>
<td>-0.13</td>
<td>0.258</td>
<td></td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.603</td>
<td>14</td>
<td> </td>
<td>-0.22</td>
<td> </td>
<td>NA</td>
<td>0.784</td>
<td>14</td>
<td> </td>
<td>-0.11</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>0.657</td>
<td>37</td>
<td> </td>
<td>-0.18</td>
<td> </td>
<td>NA</td>
<td>0.851</td>
<td>36</td>
<td> </td>
<td>-0.07</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.547</td>
<td>17</td>
<td> </td>
<td>-0.26</td>
<td> </td>
<td>NA</td>
<td>0.576</td>
<td>17</td>
<td> </td>
<td>-0.24</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium fluoride</td>
<td>79.8</td>
<td> </td>
<td>22</td>
<td>1.90</td>
<td>0.016</td>
<td> </td>
<td>47.4</td>
<td> </td>
<td>15</td>
<td>1.68</td>
<td>0.313</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>61.3</td>
<td>9</td>
<td></td>
<td>1.79</td>
<td> </td>
<td>0.007</td>
<td>48.7</td>
<td>14</td>
<td> </td>
<td>1.69</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>96.1</td>
<td>18</td>
<td> </td>
<td>1.98</td>
<td> </td>
<td>0.019</td>
<td>39.7</td>
<td>24</td>
<td> </td>
<td>1.60</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>82.0</td>
<td>7</td>
<td> </td>
<td>1.91</td>
<td> </td>
<td>0.463</td>
<td>53.7</td>
<td>13</td>
<td> </td>
<td>1.73</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium hypochlorite</td>
<td>1211</td>
<td> </td>
<td>57</td>
<td>3.08</td>
<td>0.040</td>
<td> </td>
<td>1580</td>
<td> </td>
<td>20</td>
<td>3.20</td>
<td>0.313</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>823</td>
<td>13</td>
<td> </td>
<td>2.92</td>
<td> </td>
<td>0.257</td>
<td>1863</td>
<td>31</td>
<td> </td>
<td>3.27</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>805</td>
<td>46</td>
<td> </td>
<td>2.91</td>
<td> </td>
<td>0.119</td>
<td>1243</td>
<td>46</td>
<td> </td>
<td>3.09</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>2005</td>
<td>44</td>
<td> </td>
<td>3.30</td>
<td> </td>
<td>0.015</td>
<td>1633</td>
<td>11</td>
<td> </td>
<td>3.21</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium oxalate</td>
<td>40.8</td>
<td> </td>
<td>23</td>
<td>1.61</td>
<td>0.643</td>
<td> </td>
<td>355</td>
<td> </td>
<td>1</td>
<td>2.55</td>
<td>0.926</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>42.0</td>
<td>41</td>
<td> </td>
<td>1.62</td>
<td> </td>
<td>NA</td>
<td>355</td>
<td>15</td>
<td> </td>
<td>2.55</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>31.0</td>
<td>28</td>
<td> </td>
<td>1.49</td>
<td> </td>
<td>NA</td>
<td>350</td>
<td>42</td>
<td> </td>
<td>2.54</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>49.5</td>
<td>53</td>
<td> </td>
<td>1.69</td>
<td> </td>
<td>NA</td>
<td>360</td>
<td>26</td>
<td> </td>
<td>2.56</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Sodium selenate</td>
<td>34.5</td>
<td> </td>
<td>60</td>
<td>1.54</td>
<td>&lt;0.001</td>
<td> </td>
<td>11.2</td>
<td> </td>
<td>40</td>
<td>1.05</td>
<td>0.134</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>12.7</td>
<td>13</td>
<td> </td>
<td>1.10</td>
<td> </td>
<td>&lt;0.001</td>
<td>7.47</td>
<td>12</td>
<td> </td>
<td>0.87</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>54.2</td>
<td>19</td>
<td> </td>
<td>1.73</td>
<td> </td>
<td>&lt; 0.001</td>
<td>16.1</td>
<td>59</td>
<td> </td>
<td>1.21</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>36.5</td>
<td>14</td>
<td> </td>
<td>1.56</td>
<td> </td>
<td>0.026</td>
<td>10.0</td>
<td>13</td>
<td> </td>
<td>1.00</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Strychnine</td>
<td>199</td>
<td> </td>
<td>83</td>
<td>2.30</td>
<td>&lt;0.001</td>
<td> </td>
<td>69.3</td>
<td> </td>
<td>39</td>
<td>1.84</td>
<td>0.364</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>389</td>
<td>21</td>
<td> </td>
<td>2.59</td>
<td> </td>
<td>&lt;0.001</td>
<td>100</td>
<td>76</td>
<td> </td>
<td>2.00</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>124</td>
<td>16</td>
<td> </td>
<td>2.09</td>
<td> </td>
<td>0.018</td>
<td>52.5</td>
<td>53</td>
<td> </td>
<td>1.72</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>83.5</td>
<td>6</td>
<td> </td>
<td>1.92</td>
<td> </td>
<td>&lt;0.001</td>
<td>55.1</td>
<td>6</td>
<td> </td>
<td>1.74</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Thallium Sulfate</td>
<td>7.50</td>
<td> </td>
<td>72</td>
<td>0.88</td>
<td>0.165</td>
<td> </td>
<td>0.16</td>
<td> </td>
<td>23</td>
<td>-0.80</td>
<td>0.405</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>2.80</td>
<td>24</td>
<td> </td>
<td>0.45</td>
<td> </td>
<td>NA</td>
<td>0.198</td>
<td>51</td>
<td> </td>
<td>-0.70</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>13.4</td>
<td>78</td>
<td> </td>
<td>1.13</td>
<td> </td>
<td>NA</td>
<td>0.153</td>
<td>20</td>
<td> </td>
<td>-0.82</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>6.30</td>
<td>28</td>
<td> </td>
<td>0.80</td>
<td> </td>
<td>NA</td>
<td>0.127</td>
<td>16</td>
<td> </td>
<td>-0.90</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Trichloroacetic acid</td>
<td>928</td>
<td> </td>
<td>27</td>
<td>2.97</td>
<td>0.005</td>
<td> </td>
<td>427</td>
<td> </td>
<td>24</td>
<td>2.63</td>
<td>0.134</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>762</td>
<td>13</td>
<td> </td>
<td>2.88</td>
<td> </td>
<td>0.022</td>
<td>348</td>
<td>18</td>
<td> </td>
<td>2.54</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>1220</td>
<td>6</td>
<td> </td>
<td>3.09</td>
<td> </td>
<td>0.002</td>
<td>541</td>
<td>28</td>
<td> </td>
<td>2.73</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>801</td>
<td>14</td>
<td> </td>
<td>2.90</td>
<td> </td>
<td>0.069</td>
<td>394</td>
<td>13</td>
<td> </td>
<td>2.60</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>1,1,1-Trichloroethane</td>
<td>15538</td>
<td> </td>
<td>52</td>
<td>4.19</td>
<td>&lt;0.001</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>8137</td>
<td>7</td>
<td> </td>
<td>3.91</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>21250</td>
<td>11</td>
<td> </td>
<td>4.33</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>9827</td>
<td>2</td>
<td> </td>
<td>3.99</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Triethylenemelamine</td>
<td>0.568</td>
<td> </td>
<td>135</td>
<td>-0.25</td>
<td>&lt;0.001</td>
<td> </td>
<td>1.95</td>
<td> </td>
<td>12</td>
<td>0.29</td>
<td>0.562</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.086</td>
<td>11</td>
<td> </td>
<td>-1.07</td>
<td> </td>
<td>&lt;0.001</td>
<td>1.69</td>
<td>57</td>
<td> </td>
<td>0.23</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>1.45</td>
<td>18</td>
<td> </td>
<td>0.16</td>
<td> </td>
<td>&lt;0.001</td>
<td>2.03</td>
<td>23</td>
<td> </td>
<td>0.31</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.169</td>
<td>29</td>
<td> </td>
<td>-0.77</td>
<td> </td>
<td>0.002</td>
<td>2.13</td>
<td>23</td>
<td> </td>
<td>0.33</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Triphenyltin hydroxide</td>
<td>0.022</td>
<td> </td>
<td>29</td>
<td>-1.66</td>
<td>0.688</td>
<td> </td>
<td>0.013</td>
<td> </td>
<td>55</td>
<td>-1.89</td>
<td>0.088</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>0.026</td>
<td>17</td>
<td> </td>
<td>-1.59</td>
<td> </td>
<td>NA</td>
<td>0.021</td>
<td>32</td>
<td> </td>
<td>-1.68</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>0.026</td>
<td>81</td>
<td> </td>
<td>-1.59</td>
<td> </td>
<td>NA</td>
<td>0.007</td>
<td>106</td>
<td> </td>
<td>-2.15</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>0.015</td>
<td>55</td>
<td> </td>
<td>-1.83</td>
<td> </td>
<td>NA</td>
<td>0.011</td>
<td>32</td>
<td> </td>
<td>-1.96</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Valproic acid</td>
<td>1177</td>
<td> </td>
<td>76</td>
<td>3.07</td>
<td>&lt; 0.001</td>
<td> </td>
<td>533</td>
<td> </td>
<td>28</td>
<td>2.73</td>
<td>0.081</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>547</td>
<td>12</td>
<td> </td>
<td>2.74</td>
<td> </td>
<td>NA</td>
<td>468</td>
<td>25</td>
<td> </td>
<td>2.67</td>
<td> </td>
<td>0.331</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>1807</td>
<td>10</td>
<td> </td>
<td>3.26</td>
<td> </td>
<td>NA</td>
<td>702</td>
<td>23</td>
<td> </td>
<td>2.85</td>
<td> </td>
<td>0.032</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>430</td>
<td>17</td>
<td> </td>
<td>2.63</td>
<td> </td>
<td>0.135</td>
</tr>
<tr class="even">
<td>Verapamil HCl</td>
<td>35.2</td>
<td> </td>
<td>10</td>
<td>1.55</td>
<td>0.230</td>
<td> </td>
<td>68.7</td>
<td> </td>
<td>14</td>
<td>1.84</td>
<td>0.624</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>32.0</td>
<td>18</td>
<td> </td>
<td>1.51</td>
<td> </td>
<td>NA</td>
<td>60.5</td>
<td>22</td>
<td> </td>
<td>1.78</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>34.6</td>
<td>5</td>
<td> </td>
<td>1.54</td>
<td> </td>
<td>NA</td>
<td>79.4</td>
<td>42</td>
<td> </td>
<td>1.90</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>38.9</td>
<td>11</td>
<td> </td>
<td>1.59</td>
<td> </td>
<td>NA</td>
<td>66.2</td>
<td>8</td>
<td> </td>
<td>1.82</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>Xylene</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
</tr>
<tr class="odd">
<td>ECBC</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="even">
<td>FAL</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td>NA</td>
<td>NA</td>
<td> </td>
<td>NA</td>
<td> </td>
<td>NA</td>
</tr>
<tr class="odd">
<td>IIVS</td>
<td>724</td>
<td>12</td>
<td> </td>
<td>2.86</td>
<td> </td>
<td>NA</td>
<td>486</td>
<td>38</td>
<td> </td>
<td>2.69</td>
<td> </td>
<td>NA</td>
</tr>
</tbody>
</table>

^1^Results reported on the same row with chemical names are the means of
all the laboratories. Results reported on the same row as laboratories
are the laboratory means.

^2^p \< 0.01 indicated statistical significance.

^3^Contrasts were performed if ANOVA was significant (p \< 0.01) to
determine which laboratory was different from the other two
laboratories. Significant contrasts were denoted by p \< 0.01. If only
two laboratories reported results, no contrast tests were necessary.

Abbreviations: Laboratories: ECBC- U.S. Army Edgewood Chemical
Biological Center; FAL -- FRAME Alternatives Laboratory; IIVS --
Institute for In Vitro Sciences. NA - no acceptable IC~50~ results
reported or calculation was not performed (e.g., for contrast results).

Table 7-4 Reference Substances with Significant Differences between
Laboratories for 3T3 NRU Test Method Results

+---------------------+-------------+-----------+-----------+---------+
| **Reference         | **          |           |           | **Insol |
| Substance**         | Significant |           |           | uble/** |
|                     | Contrast    |           |           |         |
|                     | R           |           |           | *       |
|                     | esults^1^** |           |           | *Volati |
|                     |             |           |           | le^2^** |
+---------------------+-------------+-----------+-----------+---------+
|                     | **ECBC**    | **FAL**   | **IIVS**  |         |
+---------------------+-------------+-----------+-----------+---------+
| Acetylsalicylic     |             | H         | L         |         |
| acid                |             |           |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Arsenic trioxide    |             | L         | H         | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Busulfan            |             | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Chloral hydrate     | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Chloramphenicol     | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Citric acid         | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Colchicine          | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Cupric sulfate      | X           | H         | L         |         |
| pentahydrate        |             |           |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Dibutyl phthalate   |             | H         | L         | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Dichlorvos          | L           | H         |           | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Disulfoton^3^       |             |           |           | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Ethylene glycol     | L           |           |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Glutethimide        |             | H         | L         |         |
+---------------------+-------------+-----------+-----------+---------+
| Haloperidol         |             | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Meprobamate         | L           | H         | X         |         |
+---------------------+-------------+-----------+-----------+---------+
| Phenylthiourea      | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Potassium cyanide   | L           | H         | X         | Prec    |
|                     |             |           |           | ipitate |
|                     |             |           |           | /Vol    |
|                     |             |           |           | atility |
+---------------------+-------------+-----------+-----------+---------+
| Procainamide HCl    | L           |           | H         |         |
+---------------------+-------------+-----------+-----------+---------+
| 2-Propanol          | L           | X         | H         | Vol     |
|                     |             |           |           | atility |
+---------------------+-------------+-----------+-----------+---------+
| Propylparaben       |             | H         | L         |         |
+---------------------+-------------+-----------+-----------+---------+
| Sodium selenate     | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Strychnine          | H           |           | L         | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Trichloroacetic     |             | H         |           |         |
| acid                |             |           |           |         |
+---------------------+-------------+-----------+-----------+---------+
| 1,1,1               |             |           |           | Prec    |
| -Trichloroethane^4^ |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Triethylenemelamine | L           | H         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Valproic acid^5^    |             |           |           | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+

^1^Laboratories significantly different from the other two at p \< 0.01.
H -- Laboratory reported the highest mean IC~50~. L -- Laboratory
reported the lowest mean IC~50~. X -- Laboratory reported a mean IC~50~
between the values of the other two laboratories.

^2^From **Table 5-8**. Precipitate reported by at least one laboratory
is indicated by "Precipitate". Use of plate sealers by at least one
laboratory to prevent volatile contamination of control wells indicated
by "Volatility".

^3^Significant ANOVA (p \< 0.01), but no contrast analysis since only
two laboratories (ECBC and IIVS) reported IC~50~ values.

^4^Significant ANOVA (p \< 0.01), but no contrast results since only two
laboratories (FAL and IIVS) reported IC~50~ values.

^5^Significant ANOVA (p \< 0.01), but no contrast results since only two
laboratories (ECBC and FAL) reported IC~50~ values.

Laboratories: ECBC- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

For the 26 substances that yielded significantly different results among
the laboratories, contrast analyses indicated that ECBC and FAL were
frequently different from the other laboratories. ECBC tended to report
the lowest IC~50~ values among the laboratories while FAL tended to
report the highest values of the three laboratories. ECBC reported
significantly different results from the other two laboratories for 15
of the 26 substances. For 13 of the 15 substances, ECBC reported the
lowest mean IC~50~ value among the three laboratories. FAL reported
significantly different results from the other two laboratories for 20
of the 26 substances. For 18 of the 20 substances, FAL reported the
highest mean IC~50~ value among the three laboratories. IIVS reported
significantly different results for 11 of the 26 substances, with no
great majority of highest or lowest IC~50~ values.

*Differences Among the Laboratories for the NHK NRU Test Method*

The ANOVA results in **Table 7-3** indicate that there were
statistically significant (p \< 0.01) laboratory differences for seven
substances. These substances are listed in **Table 7-5** along with
columns showing the laboratory statistically significantly differing
from the other two laboratories (as indicated by the contrast results),
and indications of whether any laboratory reported insolubility or
volatility during conduct of the assay. Insolubility was reported for
three of the seven substances.

Table 7-5 Reference Substances with Significant Differences between
Laboratories for NHK NRU Test Method Results

+---------------------+-------------+-----------+-----------+---------+
| **Reference         | **          |           |           | *       |
| Substance**         | Significant |           |           | *Solubi |
|                     | Contrast    |           |           | lity/** |
|                     | R           |           |           |         |
|                     | esults^1^** |           |           | **V     |
|                     |             |           |           | olatili |
|                     |             |           |           | ty^2^** |
+---------------------+-------------+-----------+-----------+---------+
|                     | **ECBC**    | **FAL**   | **IIVS**  |         |
+---------------------+-------------+-----------+-----------+---------+
| Arsenic trioxide    |             | L         | H         | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Citric acid         | H           | L         |           | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Digoxin             | H           | L         |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Dimethylformamide   | H           |           | L         |         |
+---------------------+-------------+-----------+-----------+---------+
| Disulfoton          | L           | H         |           | Prec    |
|                     |             |           |           | ipitate |
+---------------------+-------------+-----------+-----------+---------+
| Methanol^3^         |             |           |           |         |
+---------------------+-------------+-----------+-----------+---------+
| Propranolol HCl     |             | H         | L         |         |
+---------------------+-------------+-----------+-----------+---------+

^1^Laboratories significantly different from the other two at p \< 0.01.
H -- Laboratory reported the highest mean IC~50~. L -- Laboratory
reported the lowest mean IC~50~. X -- Laboratory reported a mean IC~50~
between the values of the other two laboratories.

^2^From **Table 5-8**. Precipitate reported by at least one laboratory
is indicated by "Precipitate". Use of plate sealers by at least one
laboratory to prevent volatile contamination of control wells indicated
by "Volatility".

^3^Significant ANOVA (p \< 0.01), but no contrast results since only two
laboratories (FAL and IIVS) reported IC~50~ values.

Laboratories: ECBC -- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

For the seven substances that yielded significantly different results
among the laboratories, ECBC and FAL were frequently different from the
other laboratories. ECBC tended to report the highest IC~50~ value among
the laboratories (4/7 substances) while FAL tended to report the lowest
values among the three laboratories (3/7 substances).

7.2.2 [CV Results for the 3T3 and NHK NRU Test Methods]{.underline}

CV was calculated as described in Section **5.3.3**. **Table 7-3**
provides the intra- and inter-laboratory CV values for individual
substances. **Table 7-6** summarizes the CV results for each test
method. **Table 7-6** shows that median and mean CV values were often
similar. Median CV values appeared always lower than the corresponding
means, which indicated that large individual CV values skewed the CV
distributions somewhat to the right.

*Intralaboratory CV*

**Table 7-6** shows that both test methods had similar ranges for the
intralaboratory CV. The mean intralaboratory CV values were the same,
26%. The median intralaboratory CVs were also similar: 23% for the 3T3
NRU test method and 24% for the NHK NRU test method. Of the three
laboratories, FAL had the highest mean and median CV for both test
methods and IIVS had the lowest mean and median CV for both test
methods.

*Interlaboratory CV*

The mean and median interlaboratory CV for the reference substances was
lower for the NHK NRU test method (mean = 28%; median = 21%) than for
the 3T3 NRU test method (mean = 46%; median = 40%) (see **Table 7-6**).

Table 7-6 Summary of CV Results for the 3T3 and NHK NRU Test Methods

  ----------------- ---------- ---------- ------------ ----------- ---------- ---------- ------------ -----------
  **CV**            **3T3 NRU                                      **NHK NRU                          
                    Test                                           Test                               
                    Method**                                       Method**                           

                    **N**      **Mean**   **Median**   **Range**   **N**      **Mean**   **Median**   **Range**

  Intralaboratory   202        26%        23%          1-122%      208        26%        24%          1-129%
  CV                                                                                                  

  ECBC              68         23%        17%          2-95%       69         23%        19%          2-76%

  FAL               66         33%        30%          1-98%       69         42%        32%          1-129%

  IIVS              68         21%        13%          1-122%      70         14%        13%          1-38%

  Interlaboratory   68         46%        40%          2-135%      68         28%        21%          1-99%
  CV                                                                                                  
  ----------------- ---------- ---------- ------------ ----------- ---------- ---------- ------------ -----------

Abbreviations: N- number of values. Laboratories: ECBC- U.S. Army
Edgewood Chemical Biological Center; FAL -- FRAME Alternatives
Laboratory; IIVS -- Institute for In Vitro Sciences.

Note: For the 3T3 NRU test method, the following laboratories/substances
did not obtain sufficient IC~50~ data for the calculation of an
intralaboratory CV: carbon tetrachloride at any laboratory; disulfoton
at FAL; gibberellic acid at FAL; lithium carbonate at FAL and IIVS;
methanol at any laboratory; 1,1,1-trichloroethane at ECBC; valproic acid
at IIVS; and xylene at ECBC and FAL. For the NHK assay, the following
laboratories/substances did not obtain sufficient IC~50~ data for the
calculation of an intralaboratory CV: carbon tetrachloride at any
laboratory; methanol at ECBC; 1,1,1-trichloroethane at FAL and IIVS; and
xylene at ECBC and FAL. For the 3T3 NRU test method, the following
substances did not obtain sufficient IC~50~ data for the calculation of
an interlaboratory CV: carbon tetrachloride, lithium carbonate;
methanol; and xylene. For the NHK assay, the following substances did
not yield sufficient IC~50~ data for the calculation of an
interlaboratory CV: carbon tetrachloride; 1,1,1-trichloroethane; and
xylene.

*Variation of CV with Chemical Property*

To identify the chemical characteristics that may yield high or low CV
values, CV values were analyzed to determine their association with the
following chemical attributes: physical state (i.e., solid or liquid),
solubility, volatility, chemical class, GHS acute oral toxicity class
(UN 2005), molecular weight, log Kow, IC~50~, and boiling point. For
categorical characteristics such as physical form, solubility (i.e.,
precipitate/no precipitate), volatile/not volatile, and chemical class,
the mean CV values and CV ranges for the groups were compared to one
another and to the overall mean CV and CV range for each test method. No
statistical analyses were performed. For chemical characteristics
measured by continuous variables, such as molecular weight, log K~ow~,
and IC~50~, and boiling point, Spearman correlation analyses were
performed.

*Results of Intralaboratory CV Analysis*

**Table 7-7** shows the analysis of intralaboratory CV. The analysis of
intralaboratory CV uses one mean intralaboratory CV for each reference
substances that was calculated from the intralaboratory CV values from
each laboratory. With the exception of the amides, which had relatively
low intralaboratory CV values (for both 3T3 and NHK NRU test methods),
and organophosphates and halogenated hydrocarbons (for the 3T3 NRU test
method only), which had relatively high intralaboratory CV values, there
seemed to be little difference in CV values for the categorical
physical/chemical/toxicological attributes. The mean intralaboratory CV
values for solids and liquids were similar (26 vs. 24% for the 3T3 NRU
test method; 27 vs. 23% for the NHK NRU test method). The mean
intralaboratory CV values for reference substances for which
precipitates were observed were similar to the mean intralaboratory CV
values for substances for which no precipitates were observed (29 vs.
23% for the 3T3 NRU test method; 24 vs. 27% for the NHK NRU test
method). The mean intralaboratory CV values for substances that
exhibited volatility (i.e., indicated by laboratory use of film plate
sealers to prevent contamination of control wells) were relatively
similar to those that did not (31 vs. 24% for the 3T3 NRU test method;
27 vs. 26% for the NHK NRU test method). Similarly, the substances
grouped by GHS toxicity category (UN 2005) had mean intralaboratory CV
values that were similar (19-33% for the 3T3 NRU test method; 18-31% for
the NHK NRU test method) to the overall mean CV values (26% for both the
3T3 and NHK NRU test methods).

Reference substances in the amide chemical class had unusually low mean
intralaboratory CV values for both the 3T3 NRU test method (13%) and NHK
NRU test method (10%) compared with the overall mean CV (26% for both
test methods), but there were only three substances in the class
(acetaminophen, dimethylformamide, and procainamide HCl). Reference
substances in the organophosphate chemical class had unusually high mean
intralaboratory CV values for the 3T3 NRU test method (46%), but not for
the NHK NRU test method (26%) compared with the overall mean CV (26% for
the 3T3 and NHK NRU test methods). There were only three substances in
the class (dichlorvos, disulfoton, and parathion), but two of the three
substances had relatively high mean intralaboratory CV values (17, 48
and 71%). Halogenated hydrocarbons also had high mean intralaboratory CV
for the 3T3 NRU test method (46%), but not for the NHK NRU test method
(14%) compared with the overall mean intralaboratory CV for each test
method (26%). However, the mean intralaboratory CV for the 3T3 NRU test
method was calculated from only two values; 7% for 1,1,1-trichloroethane
and 84% for lindane. No laboratory obtained sufficient toxicity for the
calculation of an IC~50~ for the carbon tetrachloride, the third
halogenated hydrocarbon.

**Table 7-7 Intralaboratory CV by Chemical Characteristics for the 3T3
and NHK NRU Test Methods**

  --------------------- ---------- ----------- ----------- ---------- ------------ ----------
  **Class/Attribute**   **3T3 NRU                          **NHK NRU               
                        Test                               Test                    
                        Method**                           Method**                

                        **N^a^**   **Range**   **Mean**    **N^b^**   **Range**    **Mean**

  All chemicals         70         1-122%      26%         71         1-129%       26%

  **Chemical form**                                                                

  Solid                 53         4-84        26          53         6-50         27

  Liquid                17         6-71        24          18         2-40         23

  **Solubility**                                                                   

  Precipitate^c^        24         7-84        29          2^a^       2-47         24

  No precipitate        46         4-55        23          50         7-57         27

  **Volatility^d^**                                                                

  Volatile              10         6-84        31          9          11-50        27

  Nonvolatile           62         4-71        24          63^b^      2-57         26

  **Chemical Class**                                                               

  Alcohols              9          6-42        22          10         10-37        21

  Carboxylic acids      12         10-41       20          12         7-48         26

  Heterocyclics         14         6-59        30          14         13-50        31

  Organophosphorous     3          17-71       46          3          20-32        26

  Amides                3          4-28        13          3          2-16         10

  Halogenated           2          7-84        46          2          7-21         14
  hydrocarbons                                                                     

  Inorganics            15         9-43        24          15         6-50         29

  **Toxicity Class**                                                               

  ≤ 5 mg/kg             7          9-71        33          7          20-40        30

  \> 5 - ≤ 50           12         13-59       32          12         12-50        31

  \> 50 - ≤ 300         12         11-84       33          12         17-37        25

  \> 300 - ≤ 2000       16         4-51        21          16         6-57         25

  \> 2000 - ≤ 5000      10^a^      9-32        19          10^a^      7-50         31

  \> 5000               13^b^      6-42        19          14         2-40         18

  **Correlations**      **N**      **r~s~**    **P value** **N**      **r~s~**     **P
                                                                                   value**

  Molecular weight      70^a,b^    0.323       0.006       71^b^      0.199        0.097

  Log K~ow~             50^e^      0.117       0.421       51^e^      0.311        0.026

  IC~50~                70^a,b^    -0.436      0.0002      71^b^      -0.362       0.002

  Boiling point         27         0.576       0.002       28         0.277        0.154
  --------------------- ---------- ----------- ----------- ---------- ------------ ----------

^a^One intralaboratory CV for each chemical was calculated by averaging
the CV values for the laboratories that reported sufficient data for the
calculation of a CV. No CV was calculable for carbon tetrachloride or
methanol.

^b^One intralaboratory CV for each chemical was calculated by averaging
the CV values for the laboratories that reported sufficient data for the
calculation of a CV. No CV was calculable for carbon tetrachloride.

^c^Denoted by laboratory reports of precipitate in the stock reference
substance solutions or in cell culture (see **Table 5-8**).

^d^Denoted by laboratory reports of using plate sealers to avoid
contamination of the VC wells (see **Table 5-8**).

^e^Number of reference substances with CV values and log K~ow~ data.

^f^Number of reference substances with CV values and boiling point data.

For the characteristics amenable to correlation analysis, none of the
correlation coefficients were large (absolute value of r~s~ \< 0.6), but
several were statistically significantly different from zero for the 3T3
NRU test method. Molecular weight (p = 0.006), IC~50~ (p = 0.0002), and
boiling point (p = 0.002) exhibited statistically significant
correlations (p \< 0.05) to intralaboratory CV for the 3T3 NRU test
method. For molecular weight, the higher molecular weight substances had
higher intralaboratory CV values. For IC~50~, however, the substances
with lower IC~50~ values had higher CV values. The inverse correlation
between intralaboratory CV values and IC~50~ is consistent with the
common observation that measurements with very low values tend to have
high CV values. The fact that substances with higher boiling points had
higher CV values was consistent with the categorical analysis of
volatility. The substances that exhibited volatile characteristics
(i.e., high reference substance concentration wells contaminated the VC
wells) in the 3T3 NRU test method had higher mean intralaboratory CV
values (31%) than the substances that did not exhibit volatile
characteristics (24%), but the difference did not seem large.

Likewise, for the NHK NRU test method, two of the characteristics
amenable to correlation analysis were statistically significantly
different from zero, but the correlation coefficients did not have large
magnitudes (absolute value of r~s~ \< 0.4). Log K~ow~ (p = 0.026) and
IC~50~ (p = 0.002) exhibited statistically significant correlations (p
\< 0.05) to intralaboratory CV for the NHK NRU test method. Log K~ow~
was positively correlated to the mean intralaboratory CV for each
substance, but IC~50~, was negatively correlated to the mean IC~50~ for
each substance.

*Results of Interlaboratory CV Analysis*

**Table 7-8** shows the analysis of interlaboratory CV. With the
exception of chemical class, there seemed to be little difference in
interlaboratory CV values for most of the categorical physical/chemical
characteristics. The mean interlaboratory CV values for solids and
liquids were similar (48 vs. 46% for the 3T3 NRU test method and 28 vs.
27% for the NHK NRU test method). The mean interlaboratory CV values for
substances for which precipitates were observed was similar to the mean
interlaboratory CV values for substances for which no precipitates were
observed (56 vs. 43% for the 3T3 NRU test method and 29 vs. 28% for the
NHK NRU test method). The mean interlaboratory CV values for substances
that exhibited volatile characteristics appeared similar to those that
did not (51 vs. 46% for the 3T3 NRU test method and 32 vs. 28% for the
NHK NRU test method).

Reference substances in the amide chemical class had unusually low mean
interlaboratory CV values for both the 3T3 NRU test method (15%) and NHK
NRU test method (16%) compared with the overall mean interlaboratory CV
(46% for the 3T3 NRU test method and 28% for the NHK NRU test method).
Chemicals in the organophosphate chemical class had unusually high mean
interlaboratory CV values for the 3T3 NRU test method (74%) and
moderately higher mean interlaboratory CV values for the NHK NRU test
method (42%) compared with the overall mean interlaboratory CV (46% for
the 3T3 NRU test method and 28% for the NHK NRU test method). The high
mean interlaboratory CV value for organophosphates in the NHK NRU test
method, however, was produced largely by the high interlaboratory CV of
99% for disulfoton. The interlaboratory CV values for dichlorvos and
parathion were 20% and 8%, respectively. Heterocyclic compounds also had
higher mean interlaboratory CV values for the 3T3 NRU test method but
not for the NHK NRU test method. As a group, the 14 heterocyclic
compounds had a mean interlaboratory CV of 61% while the overall mean
interlaboratory CV for the 3T3 NRU test method was 46%. Although there
were a few low CV values (e.g., 8, 18) in the heterocyclic group, there
were seven values greater than the overall mean CV of 46%. The median
interlaboratory CV for the heterocyclic group was 52%.

Table 7-8 Interlaboratory CV by Chemical Characteristics for the 3T3 and
NHK NRU Test Methods

  --------------------- ---------- ----------- ---------- ---------- ------------ ----------
  **Class/Attribute**   **3T3 NRU                         **NHK NRU               
                        Test                              Test                    
                        Method**                          Method**                

                        **N**      **Range**   **Mean**   **N**      **Range**    **Mean**

  All chemicals         68^a^      2-135%      46%        69^b^      1-99%        28%

  **Chemical Form**                                                               

  Solids                52         3-135       48         53         1-91         28

  Liquids               16         6-124       46         16         1-99         27

  **Solubility**                                                                  

  Precipitate^c^        22         3-127       56         19         1-99         29

  No precipitate        47         3-135       43         50         1-88         28

  **Volatility**                                                                  

  Volatile^d^           10         21-127      51         9          8-86         32

  Nonvolatile           58         3-135       46         60         1-99         28

  **Chemical Class**                                                              

  Alcohols              9          12-119      38         10         11-42        22

  Carboxylic acids      12         12-124      46         12         1-61         27

  Heterocyclics         14         8-135       61         14         5-85         32

  Organophosphorous     3          57-111      74         3          8-99         42

  Amides                3          6-28        15         3          13-19        16

  Halogenated           2          52-58       55         1          20           20
  hydrocarbons                                                                    

  Inorganics            14         3-127       48         15         4-91         29

  **Toxicity Class**                                                              

  ≤ 5 mg/kg             7          12-135      69         7          12-99        37

  \> 5 - ≤ 50           12         33-127      78         12         8-91         41

  \> 50 - ≤ 300         12         8-120       37         12         10-41        26

  \> 300 - ≤ 2000       15         11-85       38         15         1-61         20

  \> 2000 - ≤ 5000      9          3-69        29         9          1-85         27

  \> 5000               13         3-124       39         13         2-44         25

  **Correlations**                 **r~s~**    **P                   **r~s~**     **P
                                               value**                            value**

  Molecular weight      68         0.193       0.115      69         0.136        0.265

  Log K~ow~             49^e^      0.194       0.182      49         0.170        0.244

  IC~50~                68         -0.295      0.015      69         -0.271       0.024

  Boiling point         24^f^      0.467       0.021      26         -0.131       0.525
  --------------------- ---------- ----------- ---------- ---------- ------------ ----------

^a^The following chemicals did not have sufficient IC~50~ data for the
calculation of an interlaboratory CV: carbon tetrachloride, lithium
carbonate; methanol; and xylene.

^b^The following substances did not yield sufficient IC~50~ data for the
calculation of an interlaboratory CV: carbon tetrachloride;
1,1,1-trichloroethane; and xylene.

^c^Denoted by laboratory reports of precipitate in the stock reference
substance solutions or in cell culture (see **Table 5-8**).

^d^Denoted by laboratory reports of using plate sealers to avoid
contamination of the VC wells (see **Table 5-8**).

^e^Number of reference substances with CV values and log K~ow~ data.

^f^Number of reference substances with CV values and boiling point data.

Mean interlaboratory CV values tended to be large for chemicals in the
most toxic GHS acute categories, especially for the 3T3 NRU test method.
For the 3T3 NRU test method, the mean interlaboratory CV for chemicals
in the classes for LD~50~ ≤ 5 mg/kg (69%) and 5 \< LD~50~ ≤ 50 mg/kg
(78%) were much larger than the mean overall interlaboratory CV (46%,).
For the NHK NRU test method, the mean interlaboratory CV for chemicals
in the classes for 5 \< LD~50~ ≤ 5 mg/kg (37%) and 5 \< LD~50~ ≤ 50
mg/kg (41%) were much larger than the mean overall interlaboratory CV
(28%).

For the characteristics amenable to correlation analysis, none of the
correlation coefficients were large (absolute value of r~s~ \< 0.5), but
IC~50~ (p = 0.015) and boiling point (p = 0.021) exhibited statistically
significant correlations (p \< 0.05) to interlaboratory CV for the 3T3
NRU test method. There was a negative correlation between
interlaboratory CV and IC~50~, but the correlation between boiling point
and interlaboratory CV was positive. The positive correlation of CV with
boiling point was largely consistent with the categorical analysis of
volatility. The substances that exhibited volatile characteristics in
the 3T3 NRU test method had slightly higher mean CV than for the
substances that did not exhibit volatile characteristics (51 vs. 46%).
For the NHK NRU test method, only IC~50~ was significantly correlated (p
= 0.024) to interlaboratory CV with a negative correlation (r~s~ =
-0.271).

7.2.3 [Comparison of Laboratory-Specific Linear Regression Analyses for
the Prediction of *In Vivo* Rodent LD50 Values from *In Vitro* NRU IC50
Values]{.underline}

The laboratory-specific regressions presented in **Table 6-1** of
**Section 6.1.1** were compared to one another (for each test method)
with a goodness of fit F-test as described in **Section 5.3.3.** The
comparisons indicated that the laboratory-specific regressions for both
test methods were not significantly different (p \< 0.05) from one
another. The comparison of the laboratory-specific 3T3 NRU regressions
to one another yielded p = 0.796. The comparison of the
laboratory-specific NHK NRU regressions to one another yielded p =
0.985. Because the laboratory-specific regressions were not
statistically different, data were combined into a single regression for
each test method using a geometric mean of the laboratory-specific
IC~50~ values for each substance (see **Section 6.1.1**).

7.2.4 [Laboratory Concordance for the Prediction of GHS Acute Oral
Toxicity Category]{.underline}

This section provides the percentage of substances for which the
laboratory-specific IC~50~ data yielded the same (for all three
laboratories) GHS toxicity categorization when used with the regressions
evaluated in **Sections 6.3.1** through **6.3.3**. Data for the same
reference substances for each test method were evaluated to determine
the laboratory concordance for each regression. Forty-three substances
were evaluated for the 3T3 NRU test method and 44 substances were
evaluated for the NHK NRU test method. Of the original 72 substances
tested, epinephrine bitartrate, colchicine, and propylparaben were
excluded from all analyses because they were removed from the
calculation of the RC rat-only weight regressions due to the lack of rat
oral reference LD~50~ data. The 21 substances with specific mechanisms
of toxicity in **Table 6-3** were excluded from all analyses to be
consistent with those removed from the RC rat-only weight regression
excluding substances with specific mechanisms of toxicity. These
substances have known mechanisms of toxicity that are not expected to be
active in the 3T3 or NHK cell cultures. Carbon tetrachloride, methanol,
gibberellic acid, lithium carbonate, and xylene were excluded from the
3T3 NRU evaluations because at least one laboratory failed to attain
sufficient toxicity in any test for the calculation of an IC~50~. Carbon
tetrachloride, methanol, 1,1,1-trichloroethane, and xylene were excluded
from the NHK NRU analyses because at least one laboratory failed to
attain sufficient toxicity in any test for the calculation of an IC~50~.

*Laboratory Concordance for the 3T3 and NHK NRU Test Methods with the RC
Millimole Regression*

**Appendix J** (**Table J-1** for the 3T3 NRU test method and **Table
J-3** for the NHK NRU test method) shows the laboratory concordance of
the observed (i.e., *in vivo* categories for the initial LD~50~ values
in **Table 3-2**) and predicted GHS toxicity categories for each
substance determined in each *in vitro* NRU cytotoxicity test method
using the laboratory-specific geometric mean IC~50~ values and the RC
millimole regression, log LD~50~ (mmol/kg) = 0.435 x log IC~50~ (mM) +
0.625. The observed LD~50~ values are the rodent LD~50~ values from
**Table 3-2.**

For the 43 substances that yielded IC~50~ results in all laboratories
using the 3T3 NRU test method, the laboratories agreed on the GHS
toxicity category for 31 substances (72%). The 12 substances that
produced discordant results among the laboratories were cupric sulfate
pentahydrate, cycloheximide, dimethylformamide, diquat dibromide,
phenol, phenylthiourea, sodium arsenite, sodium oxalate, sodium
selenate, thallium sulfate, triethylenemelamine, and
1,1,1-trichloroethane. The laboratory predictions for these substances
disagreed by one GHS toxicity category.

For the 44 substances that yielded IC~50~ results in all laboratories
using the NHK NRU test method, the laboratories agreed on toxicity
category for 39 substances (89%). The five substances that produced
discordant results among the laboratories were arsenic trioxide,
digoxin, ethanol, 2-propanol, and sodium arsenite. The laboratory
predictions for these substances disagreed by one toxicity category.
Laboratory concordance was greater for the NHK assay than for the 3T3
assay (89% vs 72%).

*Laboratory Concordance of the 3T3 and NHK NRU Test Methods with the RC
Rat-Only Weight Regression*

**Appendix J** (**Table J-5** for the 3T3 NRU test method and **Table
J-6** for the NHK NRU test method) shows the laboratory concordance of
the observed (i.e., *in vivo* reference categories for LD~50~ values in
**Table 4-2**) and predicted GHS toxicity categories for each substance
as determined for each test method using the laboratory-specific
geometric mean IC~50~ in the RC rat-only weight regression, log LD~50~
(mg/kg) = log IC~50~ (μg/mL) x 0.372 + 2.024, from **Table 6-2.**

For the 43 substances that yielded IC~50~ results in all laboratories
using the 3T3 NRU test method, the laboratories agreed on the GHS
toxicity category for 34 substances (79%). The nine substances that
produced discordant results among the laboratories were boric acid,
cupric sulfate pentahydrate, cycloheximide, 2-propanol, propranolol HCl,
sodium selenate, thallium sulfate, triethylenemelamine, and
1,1,1-trichloroethane. The laboratory predictions for these substances
disagreed by one GHS toxicity category.

For the 44 substances that yielded IC~50~ results in all laboratories
using the NHK NRU test method, the laboratories agreed on toxicity
category for 39 substances (89%). The five substances that produced
discordant results among the laboratories were arsenic trioxide,
digoxin, glycerol, sodium chloride, and thallium sulfate. The laboratory
predictions for these substances disagreed by one toxicity category.
Laboratory concordance was greater for the NHK assay than for the 3T3
assay (89% vs 79%).

*Laboratory Concordance of the 3T3 and NHK NRU Test Methods with the RC
Rat-Only Weight Regression Excluding Substances with Specific Mechanisms
of Toxicity*

**Appendix J** (**Table J-7** for the 3T3 NRU test method and **Table
J-8** for the NHK NRU test method) shows the laboratory concordance of
the observed (i.e., *in vivo*) and predicted GHS toxicity categories for
each substance as determined for each test method using the
laboratory-specific geometric mean IC~50~ values in the RC rat-only
weight regression after exclusion of substances with specific mechanisms
of toxicity, log LD~50~ (mg/kg) = log IC~50~ (μg/mL) x 0.357 + 2.194
(**Table 6-2**).

For the 43 substances considered in the analysis of the 3T3 NRU test
method, the three laboratories agreed on the toxicity category for 36
(84%) of the substances. The seven substances that produced discordant
results among the laboratories were boric acid, cupric sulfate
pentahydrate, diquat dibromide, sodium hypochlorite, thallium sulfate,
1,1,1-trichloroethane, and valproic acid. The laboratory predictions for
these substances disagreed by one GHS toxicity category.

The extent of laboratory concordance for the RC rat-only weight
regression after excluding substances with specific mechanisms of
toxicity was the same for the NHK NRU test method (i.e., 84%, 37/44).
The seven substances that produced discordant results among the
laboratories were arsenic trioxide, digoxin, glycerol, hexachlorophene,
mercury chloride, sodium chloride, and sodium hypochlorite. The
laboratory predictions for these substances disagreed by one GHS
toxicity category.

**7.3 Historical Positive Control Data**

The reproducibility of the positive control (SLS) data was assessed by
CV analysis, ANOVA, and linear regression over time as described in
**Section 5.3.4**. The SLS data analyzed for variability are slightly
different from those used to determine the PC acceptance limits shown in
**Table 5-2**. To get an assessment of the true variation of SLS IC~50~
values, the reproducibility analyses included IC~50~ values from SLS
tests that failed the test acceptance criterion for the IC~50~
acceptance limits determined for each study phase. These additional SLS
tests, however, passed all other test acceptance criteria. If more than
one SLS test was performed in a single day (for each test method and
laboratory), the IC~50~ values were averaged to determine a single
IC~50~ for the day so that multiple results from a single day would not
overly influence the average for each phase.

**Figure 7-1** shows the average SLS IC~50~ values for each test method,
laboratory, and study phase. Graphically, it appears that the SLS IC~50~
for the 3T3 NRU test method was relatively consistent over the entire
period of the study (approximately 2.5 years). The intralaboratory CV
values (shown in **Figure 7-1**) for the individual study phases ranged
from 5% to 24%. With the exception of the Phase Ib CV at FAL, the CV
values for each laboratory and phase were less than 20%. The
interlaboratory CV values were even smaller: 6% for Phases Ia and Ib;
10% for Phase II; and 2% for Phase III.

**Figure 7-1** shows that the SLS IC~50~ for the NHK NRU test method
tended to vary with time, but, with the exception of the SLS IC~50~
results from FAL, there appeared to be no consistent trend. The IC~50~
values from FAL, which changed NHK cell culture methods after Phase Ib
(see **Section 5.1.3**), tended to decrease over time. Although the
change in cell culture methods reduced the magnitude of the IC~50~, the
variability (as evidenced by the intralaboratory CV values shown in
**Figure 7-1**) remained relatively high (CV ≥ 34% for all FAL study
phases). The CV values for all the laboratories and study phases
indicated that the SLS IC~50~ values for the NHK NRU test method was
more variable within laboratories than the SLS IC~50~ for 3T3 NRU test
method. CV values for the SLS IC~50~ for the NHK NRU test method ranged
from 11 to 51%, with nine of the 12 values greater than 20%. The
interlaboratory CV values, which were also greater than those for the
3T3 NRU test method, were: 39% for Phase Ia; 21% for Phase Ib; and 31%
for Phase II; and 8% for Phase III.

**Figure 7-1 SLS IC~50~ for Each Laboratory and Study Phase**

a 3T3 NRU Test Method

![](media/image1.pct){width="6.24375in" height="3.4930555555555554in"}

b NHK NRU Test Method

![](media/image2.pct){width="6.24375in" height="3.41875in"}

Bars show mean IC~50~ values. Error bars show standard deviation.
Percent values above error bars are intralaboratory CVs.

Laboratories: ECBC- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

7.3.1 [ANOVA and Linear Regression Results for the 3T3 NRU Test
Method]{.underline}

*SLS IC~50~ Variation with Time*

**Table 7-9** shows the ANOVA results for SLS from the 3T3 NRU test
method. When the IC~50~ values within each laboratory were compared by
study phase (i.e., the ANOVA factor was study phase), there were no
statistically significant differences (p \< 0.01) between study phases
for any laboratory. **Table 7-10** shows that the slopes of the linear
regressions of the IC~50~ values over time (expressed as index values)
were statistically different from zero for ECBC and FAL (p = 0.001 and
0.012, respectively). Since the slopes were so small (0.000204 and
-0.000324), they were considered to be unimportant. The slope of the
IIVS regression of SLS IC~50~ over time was not statistically different
from zero (p = 0.651; **Table 7-10**), which was entirely consistent
with the ANOVA (**Table 7-9**) indicating that SLS IC~50~ from IIVS did
not vary with study phase (p = 0.854). The ANOVA with study phase as the
factor (with laboratories combined) indicated that the 3T3 NRU IC~50~
values from all the laboratories were consistent over time since data
from the various study phases were not statistically significantly
different (p = 0.304).

*Comparison of SLS IC~50~ Among the Laboratories*

When all study phases from each laboratory were combined, ANOVA, with
laboratory as the factor, indicated that the SLS IC~50~ for the 3T3 NRU
test method differed in some statistically significant fashion among the
laboratories (p \< 0.006). However, the differences between laboratories
look rather small in **Figure 7-1** since the SDs for the laboratories
clearly overlap one another.

**Table 7-9 ANOVA Results for SLS IC~50~** from the 3T3 NRU Test Method

<table>
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<col style="width: 0%" />
<col style="width: 12%" />
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<tbody>
<tr class="odd">
<td rowspan="2"><p><strong>Study Phase/</strong></p>
<p><strong>Laboratory</strong></p></td>
<td colspan="4"><strong>ECBC</strong></td>
<td colspan="5"><strong>FAL</strong></td>
<td colspan="4"><strong>IIVS</strong></td>
</tr>
<tr class="even">
<td><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
<td colspan="2"><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
<td><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
</tr>
<tr class="odd">
<td colspan="6"><em>Test for differences between phases within each
laboratory</em></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase Ia</td>
<td>-0.876</td>
<td>0.042</td>
<td>6</td>
<td>0.031</td>
<td colspan="2">-0.811</td>
<td>0.046</td>
<td>9</td>
<td>0.015</td>
<td>-0.850</td>
<td>0.034</td>
<td>7</td>
<td>0.854</td>
</tr>
<tr class="odd">
<td>Phase Ib</td>
<td>-0.864</td>
<td>0.066</td>
<td>6</td>
<td></td>
<td colspan="2">-0.846</td>
<td>0.065</td>
<td>8</td>
<td></td>
<td>-0.838</td>
<td>0.025</td>
<td>5</td>
<td></td>
</tr>
<tr class="even">
<td>Phase II</td>
<td>-0.848</td>
<td>0.027</td>
<td>16</td>
<td></td>
<td colspan="2">-0.796</td>
<td>0.057</td>
<td>19</td>
<td></td>
<td>-0.854</td>
<td>0.025</td>
<td>8</td>
<td></td>
</tr>
<tr class="odd">
<td>Phase III</td>
<td>-0.842</td>
<td>0.036</td>
<td>36</td>
<td></td>
<td colspan="2">-0.851</td>
<td>0.066</td>
<td>27</td>
<td></td>
<td>-0.844</td>
<td>0.041</td>
<td>23</td>
<td></td>
</tr>
<tr class="even">
<td colspan="5"><em>Test for differences between laboratories (phases
combined)</em></td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>All Phases</td>
<td>-0.849</td>
<td>0.039</td>
<td>64</td>
<td>0.006</td>
<td colspan="2">-0.826</td>
<td>0.062</td>
<td>63</td>
<td></td>
<td>-0.847</td>
<td>0.035</td>
<td>44</td>
<td></td>
</tr>
<tr class="even">
<td colspan="5"><em>Test for differences between phases (laboratories
combined)</em></td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Phase Ia</td>
<td>-0.839</td>
<td>0.049</td>
<td>22</td>
<td>0.304</td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase Ib</td>
<td>-0.850</td>
<td>0.056</td>
<td>19</td>
<td></td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Phase II</td>
<td>-0.831</td>
<td>0.047</td>
<td>34</td>
<td></td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase III</td>
<td>0.845</td>
<td>0.045</td>
<td>86</td>
<td></td>
<td colspan="2"></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
</tbody>
</table>

^1^Statistically significant at p \< 0.01.

Abbreviations: N- number of values; SD -- standard deviation.
Laboratories: ECBC- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

**Table 7-10 Linear Regression Analysis of SLS IC~50~ Over Time^1^**

+----------------+------------------+-------------------+-------------+
| **Test         | **Slope**        | **P-value         | **          |
| Method/**      |                  | (Slope)^2^**      | Intercept** |
|                |                  |                   |             |
| **Laboratory** |                  |                   |             |
+----------------+------------------+-------------------+-------------+
| **3T3 NRU**    |                  |                   |             |
+----------------+------------------+-------------------+-------------+
| ECBC           | 0.000204         | 0.001             | -0.874      |
+----------------+------------------+-------------------+-------------+
| FAL            | -0.000324        | 0.012             | -0.796      |
+----------------+------------------+-------------------+-------------+
| IIVS           | 0.0000304        | 0.651             | -0.850      |
+----------------+------------------+-------------------+-------------+
| **NHK NRU**    |                  |                   |             |
+----------------+------------------+-------------------+-------------+
| ECBC           | -0.000559        | 0.002             | -1.901      |
+----------------+------------------+-------------------+-------------+
| FAL            | -0.00112         | \< 0.001          | -1.737      |
+----------------+------------------+-------------------+-------------+
| IIVS           | -0.000445        | 0.002             | -1.885      |
+----------------+------------------+-------------------+-------------+

^1^Time was expressed as index values. The index value of each test
reflected the order of testing without respect to the time lapsing
between tests.

^2^Statistically significant from zero at p \< 0.05.

Laboratories: ECBC- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

7.3.2 [ANOVA and Linear Regression Results for the NHK NRU Test
Method]{.underline}

*SLS IC~50~ Variation with Time*

**Table 7-11** shows the ANOVA results for the NHK NRU test method. When
the IC~50~ values within each laboratory were compared by study phase
(i.e., the ANOVA factor was phase), the phases were statistically
different (p \< 0.01) at each laboratory. The IC~50~ values from the
various study phases were also significantly different from one another
when the laboratory data were combined (p \< 0.001). Linear regression
analyses showed that the slopes for IC~50~ over time (expressed as an
index values) were statistically significantly greater than zero for
each laboratory (see **Table 7-10**). Since the slopes were so small
(-0.000559, -0.00112, and -0.000445), they were considered to be
unimportant.

**Table 7-11 ANOVA Results for SLS IC~50~** from the NHK NRU Test Method

<table style="width:100%;">
<colgroup>
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 9%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 9%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
</colgroup>
<tbody>
<tr class="odd">
<td rowspan="2"><p><strong>Study Phase/</strong></p>
<p><strong>Laboratory</strong></p></td>
<td colspan="4"><strong>ECBC</strong></td>
<td colspan="4"><strong>FAL</strong></td>
<td colspan="4"><strong>IIVS</strong></td>
</tr>
<tr class="even">
<td><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
<td><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
<td><strong>Log Mean IC<sub>50</sub> (mM)</strong></td>
<td><strong>SD</strong></td>
<td><strong>N</strong></td>
<td><strong>P<sup>1</sup></strong></td>
</tr>
<tr class="odd">
<td colspan="5"><em>Test for differences between phases within each
laboratory</em></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase Ia</td>
<td>-1.867</td>
<td>0.135</td>
<td>5</td>
<td>0.001</td>
<td>-1.656</td>
<td>0.125</td>
<td>5</td>
<td>&lt; 0.001</td>
<td>-1.904</td>
<td>0.060</td>
<td>12</td>
<td>&lt; 0.001</td>
</tr>
<tr class="odd">
<td>Phase Ib</td>
<td>-1.936</td>
<td>0.092</td>
<td>6</td>
<td></td>
<td>-1.829</td>
<td>0.141</td>
<td>10</td>
<td></td>
<td>-1.965</td>
<td>0.046</td>
<td>5</td>
<td></td>
</tr>
<tr class="even">
<td>Phase II</td>
<td>-2.007</td>
<td>0.109</td>
<td>11</td>
<td></td>
<td>-1.982</td>
<td>0.173</td>
<td>15</td>
<td></td>
<td>-1.863</td>
<td>0.058</td>
<td>12</td>
<td></td>
</tr>
<tr class="odd">
<td>Phase III</td>
<td>-1.990</td>
<td>0.098</td>
<td>31</td>
<td></td>
<td>-1.941</td>
<td>0.113</td>
<td>34</td>
<td></td>
<td>-1.972</td>
<td>0.070</td>
<td>19</td>
<td></td>
</tr>
<tr class="even">
<td colspan="5"><em>Test for differences between laboratories (phases
combined)</em></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>All Phases</td>
<td>-1.971</td>
<td>0.113</td>
<td>53</td>
<td>&lt; 0.001</td>
<td>-1.879</td>
<td>0.175</td>
<td>64</td>
<td></td>
<td>-1.924</td>
<td>0.073</td>
<td>48</td>
<td></td>
</tr>
<tr class="even">
<td colspan="5"><em>Test for differences between phases (laboratories
combined)</em></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Phase Ia</td>
<td>-1.833</td>
<td>0.143</td>
<td>22</td>
<td>&lt; 0.001</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase Ib</td>
<td>-1.891</td>
<td>0.125</td>
<td>21</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Phase II</td>
<td>-1.964</td>
<td>0.139</td>
<td>38</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Phase III</td>
<td>-1.971</td>
<td>0.100</td>
<td>84</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
</tbody>
</table>

^1^Statistically significant at p \< 0.01.

Abbreviations: N- number of values; SD -- standard deviation.
Laboratories: ECBC -- U.S. Army Edgewood Chemical Biological Center; FAL
-- FRAME Alternatives Laboratory; IIVS -- Institute for In Vitro
Sciences.

*Comparison of SLS IC~50~ Among the Laboratories*

The ANOVA results, with laboratory as a factor (**Table 7-11)**
indicated that the SLS IC~50~ was statistically different among the
laboratories when the data from the study phases were pooled (p \<
0.001). **Figure 7-1** shows that the SLS data from ECBC and IIVS were
rather similar for Phases Ia, Ib, and III. The SLS IC~50~ data from FAL
looks different from the other two laboratories for Phases Ia, Ib, and
II, but the bars and SDs for Phase III show that the data from all
laboratories were similar.

**7.4 Laboratory Concordance for Solvent Selection**

The solvents used to dissolve the reference substances are shown in
**Table 7-12**. For Phases Ib and II, the SMT selected the solvents to
use for cytotoxicity testing based on the solubility results provided by
BioReliance (see **Table 5-7**) using the solubility protocol in
**Appendix G2**. Despite the fact that the solubility of an individual
substance in 3T3 medium and NHK medium might be different, the SMT chose
the same solvent for both test methods, rather than choosing one for the
3T3 assay and one for the NHK assay. For example, if solubility in the
3T3 medium was ≥ 2 mg/mL and solubility in the NHK medium was \< 2
mg/mL, and the substance was soluble in DMSO at 200 mg/mL, then the SMT
selected DMSO as the solvent for cytotoxicity testing.

During Phases Ib and II, the SMT noted that BioReliance sometimes
achieved higher solubility than the cytotoxicity laboratories (e.g., see
the results for arsenic trioxide, aminopterin, and chloramphenicol in
**Table 5-7**). In an attempt to avoid the selection of a solvent for
which one or more laboratories could not achieve the desired solubility,
the SMT used the solubility data from all the laboratories to determine
solvent selections for cytotoxicity testing in Phase III. The SMT viewed
BioReliance's NHK and 3T3 media solubility results for each substance in
Phases Ib and II to be one result for media and took a similar approach
in Phase III when considering all the laboratory results to determine
the solvent to use for cytotoxicity testing. For example, if one
laboratory had achieved solubility at 2 mg/mL in medium, but the other
laboratories had not, and the substance was soluble in DMSO at 200
mg/mL, then the SMT selected DMSO as the solvent. **Table 7-12** shows
that cell culture medium was used to test as the solvent for 38
substances and DMSO was used as the solvent for 34 substances.

The solubility protocol used by the cytotoxicity laboratories failed to
guide the selection of a solvent for five substances because they were
insoluble at all concentrations tested in at least one laboratory.
Arsenic trioxide was insoluble at all the cytotoxicity laboratories.
IIVS also found sodium oxalate, strychnine, and triethylenemelamine
insoluble in any solvent, and FAL found thallium sulfate insoluble in
any solvent. To select a solvent for cytotoxicity testing of these
substances, the SMT used the solubility results from the laboratories
that did achieve solubility.

+--------------------+--------------+-----------+----------+----------+
| **Table 7-12       |              |           |          |          |
| Solvent            |              |           |          |          |
| Determinations by  |              |           |          |          |
| Laboratory**       |              |           |          |          |
+====================+==============+===========+==========+==========+
| **Reference        | **Solvent    | **ECBC**  | **FAL**  | **IIVS** |
| Substance**        | for          |           |          |          |
|                    | Testing^1^** |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Acetaminophen    | DMSO         | Medium    | Medium   | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Acetonitrile     | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Acetylsalicylic  | DMSO         | Medium    | DMSO     | Medium   |
| > acid             |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Aminopterin      | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > 5-Aminosalicylic | Medium       | Medium    | Medium   | Medium   |
| > acid             |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Amitriptyline    | DMSO         | DMSO      | DMSO     | DMSO     |
| > HCl              |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Arsenic III      | Medium       | ID        | ID       | ID       |
| > trioxide         |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Atropine sulfate | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Boric aid        | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Busulfan         | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Cadmium II       | DMSO         | DMSO      | DMSO     | DMSO     |
| > chloride         |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Caffeine         | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Carbamazepine    | DMSO         | Medium    | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Carbon           | DMSO         | Medium    | DMSO     | Medium   |
| > tetrachloride    |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Chloral hydrate  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Chloramphenicol  | DMSO         | DMSO      | DMSO     | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Citric acid      | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Colchicine       | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Cupric sulfate   | Medium       | Medium    | Medium   | Medium   |
| > pentahydrate     |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Cycloheximide    | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Dibutyl          | DMSO         | DMSO      | DMSO     | DMSO     |
| > phthalate        |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Dichlorvos       | DMSO         | Medium    | DMSO     | Medium   |
| > (DDVP)           |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Diethyl          | DMSO         | DMSO      | DMSO     | DMSO     |
| > phthalate        |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Digoxin          | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| >                  | Medium       | Medium    | Medium   | Medium   |
|  Dimethylformamide |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Diquat dibromide | Medium       | Medium    | Medium   | Medium   |
| > monohydrate      |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Disulfoton       | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Endosulfan       | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Epinephrine      | Medium       | Medium    | Medium   | Medium   |
| > bitartrate       |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Ethanol          | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Ethylene glycol  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Fenpropathrin    | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Gibberellic acid | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Glutethimide     | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Glycerol         | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Haloperidol      | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Hexachlorophene  | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Lactic acid      | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Lindane          | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Lithium I        | Medium       | Medium    | Medium   | Medium   |
| > carbonate        |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Meprobamate      | DMSO         | Medium    | Medium   | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Mercury II       | DMSO         | DMSO      | DMSO     | DMSO     |
| > chloride         |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Methanol         | DMSO         | Medium    | Medium   | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Nicotine         | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Paraquat         | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Parathion        | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Phenobarbital    | DMSO         | Medium    | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Phenol           | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Phenylthiourea   | DMSO         | DMSO      | Medium   | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Physostigmine    | DMSO         | Medium    | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Potassium I      | Medium       | Medium    | Medium   | Medium   |
| > chloride         |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Potassium        | Medium       | Medium    | Medium   | Medium   |
| > cyanide          |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Procainamide HCl | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > 2-Propanol       | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Propranolol HCl  | DMSO         | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Propylparaben    | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Sodium arsenite  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Sodium chloride  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Sodium           | Medium       | Medium    | Medium   | Medium   |
| > dichromate       |              |           |          |          |
| > dihydrate        |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Sodium fluoride  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Sodium           | Medium       | Medium    | Medium   | Medium   |
| > hypochlorite     |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Sodium oxalate   | Medium       | Medium    | Medium   | ID       |
+--------------------+--------------+-----------+----------+----------+
| > Sodium selenate  | Medium       | Medium    | Medium   | Medium   |
+--------------------+--------------+-----------+----------+----------+
| > Strychnine       | Medium       | Medium    | Medium   | ID       |
+--------------------+--------------+-----------+----------+----------+
| > Thallium I       | Medium       | Medium    | ID       | Medium   |
| > sulfate          |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Trichloroacetic  | Medium       | Medium    | Medium   | Medium   |
| > acid             |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > 1,1              | Medium       | Medium    | Medium   | Medium   |
| ,1-Trichloroethane |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > T                | DMSO         | Medium    | DMSO     | ID       |
| riethylenemelamine |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Triphenyltin     | DMSO         | DMSO      | DMSO     | DMSO     |
| > hydroxide        |              |           |          |          |
+--------------------+--------------+-----------+----------+----------+
| > Valproic acid    | DMSO         | Medium    | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Verapamil HCl    | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > Xylene           | DMSO         | DMSO      | DMSO     | DMSO     |
+--------------------+--------------+-----------+----------+----------+
| > DMSO Total       | 34           | 22        | 29       | 28       |
+--------------------+--------------+-----------+----------+----------+
| > Medium Total     | 38           | 49        | 41       | 40       |
+--------------------+--------------+-----------+----------+----------+

ID-insufficient data to select solvent.

^1^Solvents for testing as determined by the SMT and used in the study
by each laboratory: Medium = cell culture medium; DMSO = dimethyl
sulfoxide

ECBC -- US Army Edgewood Chemical Biological Center; FAL -- FRAME
Alternatives Laboratory; IIVS -- Institute for In Vitro Sciences

The cytotoxicity laboratories selected the same solvent for 55 of the 72
reference substances (76%). Excluding the five substances that were
found to be insoluble in any solvent by at least one laboratory, there
were 12 substances for which the cytotoxicity laboratories disagreed:
acetaminophen, acetylsalicylic acid, carbamazepine, carbon
tetrachloride, chloramphenicol, dichlorvos, meprobamate, methanol,
phenobarbital, phenylthiourea, physostigmine, and valproic acid. Every
laboratory reported relatively low solubility, ≤ 2 mg/mL, in medium for
these substances. Since 2 mg/mL in medium is the departure point for the
selection medium or DMSO, a small variation in results causes the
laboratories to select different solvents. The solubility of
acetaminophen, for example was reported as 2 mg/mL in culture media by
ECBC and FAL, but \< 2 mg/mL by IIVS. IIVS found it soluble in 200 mg/mL
DMSO and selected DMSO as the solvent. ECBC and FAL selected the culture
media as the solvent. The SMT selected DMSO as the solvent for
acetaminophen to be used by all laboratories.

5.  **Summary**

Intra- and inter-laboratory reproducibility were assessed using ANOVA,
CV analysis, comparison of the laboratory-specific IC~50~-LD~50~
regressions to one another (for each test method) and laboratory
concordance for the GHS acute oral toxicity category predictions. ANOVA
permits statistical comparisons of laboratories and experimental
averages, while controlling for other factors. CV analysis is an
empirical way of expressing the relative magnitudes of variability on a
standardized scale. ANOVA results for the reference substances showed
significant laboratory differences for 26 substances for the 3T3 NRU
test method and seven substances for the NHK test method.
Intralaboratory CV values were 1-122% for the 3T3 NRU test method and
1-129% for the NHK NRU test method. Mean intralaboratory CV values were
26% for both test methods, but the NHK NRU test method had a lower
interlaboratory CV (28% vs 46%). Interlaboratory CV values were 2-135%
for the 3T3 NRU test method and 1-99% for the NHK NRU test method. FAL
had the highest mean intralaboratory CV for both test methods (33% for
the 3T3 NRU test method and 42% for the NHK NRU test method).

An analysis to determine the relationship between the chemical
attributes and interlaboratory CV indicated that physical form,
solubility, and volatility had little effect on CV. CV seemed to be
related, however, to chemical class, GHS acute toxicity category,
IC~50~, and boiling point. Reference substances in the amide class had
unusually low mean interlaboratory CV values for both the 3T3 NRU test
method (15%) and NHK NRU test method (16%) compared with the overall
mean interlaboratory CV values (46% for the 3T3 NRU test method and 28%
for the NHK NRU test method). Reference substances in the
organophosphate and heterocyclic classes had unusually high mean
interlaboratory CV values for the 3T3 NRU test method (74% and 71%,
respectively), but not for the NHK NRU test method. Mean interlaboratory
CV values were large for substances in the most toxic GHS acute
categories, especially for the 3T3 NRU test method. The mean
interlaboratory CV for substances in the classes for LD~50~ ≤ 5 mg/kg
(69%) and 5 \< LD~50~ ≤ 50 mg/kg (78%) were larger than the mean overall
interlaboratory CV (46%,) for the 3T3 NRU test method. For the NHK NRU
test method, the mean interlaboratory CV was 37% for substances with
LD~50~ ≤ 5 mg/kg and 41% for substances with 5 \< LD~50~ ≤ 50 mg/kg
while the mean overall interlaboratory CV was 28%. A Spearman
correlation analysis indicated that IC~50~ was negatively correlated to
interlaboratory CV for both 3T3 (p = 0.015) and NHK (p = 0.024) NRU test
methods and that boiling point was positively correlated to
interlaboratory CV (p = 0.021) for the 3T3 NRU test method.

The analysis of interlaboratory reproducibility by evaluating the
similarity of the laboratory specific IC~50~-LD~50~ regressions
indicated that the laboratory regressions for both test methods were not
significantly different (p \< 0.05) from one another (p = 0.796 for the
3T3 NRU and p = 0.985 for the NHK NRU). The evaluation of laboratory
concordance for the prediction of GHS acute oral toxicity category when
the laboratory-specific IC~50~ data were applied to the same regression
yielded the following proportions of substances for which all
laboratories agreed on the GHS acute oral toxicity categorization:

-   78% (52/67) for the 3T3 NRU and 87% (59/68) for the NHK NRU with the
    RC regression

-   81% (52/64) for the 3T3 NRU and 91% (59/65) for the NHK NRU with the
    RC rat only weight regression

-   84% for the both test methods (36/43 for the 3T3 NRU and 37/44 for
    the NHK NRU) with the RC rat only weight regression excluding
    substances with specific mechanisms of action

ANOVA results for the positive control, SLS, IC~50~ in the 3T3 NRU test
method indicated that there were significant differences among
laboratories (p = 0.006) and but not between study phases within
laboratories (p \> 0.01). However, interlaboratory CV values, which
ranged from 2% to 10% for the study phases, indicated that the
laboratories were similar. Intralaboratory CV values for the study
phases ranged from 5% to 24%. SLS IC~50~ values for the NHK NRU test
method were more variable than those for the 3T3 NRU test method. ANOVA
results for SLS in the NHK NRU test method indicated that there were
significant differences between laboratories (p \< 0.001) and between
study phases within laboratories (p ≤ 0.001). A change in cell culture
methods at FAL decreased the SLS IC~50~ from Phase Ib to Phase II.
Intralaboratory CV values for the NHK NRU SLS IC~50~ during the various
study phases ranged from 11% to 51%. Interlaboratory CV values for SLS
in the NHK NRU test method ranged from 8% to 39%.

Cell culture medium was used as the solvent for testing 38 substances
and DMSO was used for 34 substances. The laboratory concordance in
selecting solvent for the reference substances using the solubility
protocol was 76% (55/72).

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