Table A.8.

Response–Response and Temporality concordance table for the tool compound rotenone

(a): Concentration at the target site	(b): KE1c (c): Inhibition of C I	(d): KE2c (e): Mitochondrial dysfunction	(f): KE3c (g): Impaired proteostasis	(h): KE4 (i): Degeneration of DA neurons of nigrostriatal pathway	(j): AO (k): Parkinsonian motor symptoms
5–10 nM in‐vitro [1]	+ 4–72 h [1]	+ 4–72 h [4]	+ 24 h [3]	–	–
20–30 nM ex‐vivo, rat brain concentration [4–5–2–6]	++ 4–72 h (4–5)	++ 4–72 h [4–5]	++ 24 h [3–2–6]	++a 5 weeks [2–6]	+++b 5 weeks [2–6]
100 nM in‐vitro [4]	+++ 4–72 h [4]	+++ 4–72 h [4]	+++ 24 h [3]	Above the maximum tolerated dose [2–6]	Above the maximum tolerated dose [2–6]

References: Choi et al., 2008 [1]; Betarbet et al., 2006 [2]; Chou et al., 2010 [3]; Barrientos and Moraes 1999 [4]; Okun et al., 1999 [5]; Betarbet et al., 2000 [6].

–: No data available.

+: Low severity score, ++ intermediate severity score, +++ high severity score.

^a50% of treated animals showed loss of DA neurons in SNpc.

^bAll animals affected in KE4 showed impaired motor symptoms.

^cKE 1, 2 and 3 showed a dose‐related severity in the effect and the score ++ was normalised vs. the KE4.