Table 7.
Laboratory-specific test procedures for guideline developmental neurotoxicity studies.
| Laboratory | Strain and treatment period | Motor activity | Acoustic Startle habituation a | Cognition | Brain neuropathology b | Brain morphometry c | |
|---|---|---|---|---|---|---|---|
| Acetamiprid | WIL Laboratories | Sprague-Dawley GD6 – LD21 | 60-min open-field (18.5 × 9.5 ×8 in.) photobeam SDI-System | SDI SR-Lab; accelerometer; 115 dB noise burst | Biel maze: multi-phase water-filled 8-unit T-maze | PND 11 (perfusion) PND 70 (perfusion)5 coronal sections | PND 11 and ∼PND 70: hemisphere height, FC, PC, three measures of hippocampus, height caudal pons, CB |
| Imidacloprid | Bayer Laboratory | Wistar GD0 – LD21 | 60-min figure-8 maze photobeam Coulbourn | Coulbourn; load-cell force transducer; 120 dB noise burst | Passive avoidance & M- water maze | PND 11 (immersion) PND 72 (perfusion)7 coronal sections | PND 11 and ∼PND 70: FC, PC, CP, CC, HG, CB |
| Thiacloprid | Charles River (formerly Argus) | Sprague-Dawley GD0 – LD21 | 60-min open-field (40.6 × 25.4 × 17.8 cm) | Coulbourn; load-cell force transducer; 120 dB noise burst | Passive avoidance & M- water maze | PND 11 (immersion) PND 70 (perfusion)11 coronal sections; | PND 11 and ∼PND 70: FC, PC, CS, CC, HG, CB |
| Clothianidin | Charles River (formerly Argus) | Sprague-Dawley GD0 – LD21 | 60-min open field (40.6 × 25.4 × 17.8 cm) | Coulbourn; load-cell force transducer; 120 dB noise burst | Passive avoidance and M- water maze | PND 11 (immersion) PND 83-87 (perfusion)11 coronal sections | PND 11 and ∼PND 85: FC, PC, CS, CC, HG, CB |
| Thiamethoxam | Syngenta Central Toxicology Laboratory | Wistar GD6 – LD21 | 50-min open-field (8.5 × 6×5 cm IR sensors) | SDI SR-Lab accelerometer; 110 dB noise burst | “Y”-shaped water maze | PND 11 (immersion) PND 62 (perfusion)7 coronal sections | PND 11 & ∼PND 62: FC, DC, PiC, CC, thalamus, HW, DG, CB |
| Dinotefuran | Charles River (formerly Argus) | Sprague-Dawley GD6 – LD21 | 60-min open field (40.6 × 25.4 × 17.8 cm) | Coulbourn; load-cell force transducer; 120 dB noise burst | Passive avoidance and M- water maze | PND 21 (perfusion) PND 69 (perfusion)9 coronal sections | PND 21 and ∼PND 70: FC, CS, CC, HG, CB |
a
Acoustic startle response amplitude measured as g (load cell) or V max (accelerometer).
b
In addition, neuropathology examination of peripheral nervous system tissues taken at ∼ PND 70–80 was conducted (including muscle, eye, spinal cord, proximal sciatic nerve, proximal tibial nerve and distal tibial nerve). See Supplementary Appendix I for example.
c
FC, frontal cortex; PC,parietal cortex; PiC (piriform cortex; DC, dorsal cortex; CP, caudate-putamen width; CS, corpus striatum: maximum diagonal measure of caudate-putamen & globus pallidus; CC, corpus callosum, HG hippocampal gyrus; HW, hippocampal width; DG, dentate gyrus; CB, cerebellum; C, cerebrum.