Table 1.

Dose-Setting Criteria for Male Rats

Compounda	Range-finder performed	MTD achieved (no, yes, exceeded)	Endpoint that was used to select dose levels	No. of dose levelsb
1	Yes	Yes	Body weight	3
2	Yes	No	Kidney pathology	3
3	Yes	No	Clinical signs	3
4	Yes	Yes	Body weight	3
5	No	Yes	Cholinesterase inhibition	4
6	Yes	Yes	Body weight	4
7	Yes	Yes	Liver weight	3
8	No	No	Clinical signs	3
9	Yes	Yesc	Clinical signs	3
10	No	Yesd	Limit dose (1000 mg/kg)	3
14	Yes	Yes	Clinical signs/body weight	4
15	Yes	Yes	Creatinine increases	4
16	Yes	Yes	Cholinesterase inhibition	4
17	Yes	Yes	Hepatocellular necrosis	4
18	Yes	Yes	Body weight	4
19	Yes	Yes	Body weight	4
20 (assay #1)	Yes	Exceeded	Body weight	4
20 (assay #2)	Yes	Yes	Body weight	4
21	No	Yese	Cholinesterase inhibition	3
22	No	Yese	Cholinesterase inhibition	3
23	Yes	Yes	Clinical signs	3

^aTest materials were arbitrarily assigned a “compound number,” which is consistent between this table and Table 2.

^bNumber of dose levels evaluated including controls in the male pubertal assay.

^cDose levels selected to avoid systemic toxicity that was observed at slightly higher dose levels in previous studies.

^dMaximum tolerated dose was achieved since testing was done at limit dose of 1000 mg/kg.

^eMaximum tolerated dose selected using read across to previously performed studies.