mg/kg/day. NOAEL 1 mg/kg/day. No neoplastic findings. Rat M / F 017716 (Jun 3 months PO in 2.4 / 2.8 35 / 38 Red blood cell parameters 1999); GLP; day Wistar rats; (marginal liver (marginal in ↓), ↑ 4.7 / 5.7 71 / 70 30 kinetic data weight) at HD. NOAEL 4 mg/kg/day. 0, 0.5, 1, 4 17 / 21 217 / 202 2003-1492 (Sep 6 months PO in SD 1.5 / 1.8 26 / 29 Atrophic changes in haematopoietic 2005); GLP; day rats; tissues/organs, spleen; lymphoid 8.6 / 9.4 (day 90) and 102 / 124 (day 90) 181 kinetic data tissues/organs; intestinal tract and 0, 0.3, 1.5 (↑ to 9 at 40 / 49 and 487 / 568 reproductive tissues; liver week 15), 3, 6 20 / 21 (hepatocyte focal and (mainly at 240 / 330 fatal doses) single cell necrosis). 33 / 33 342 / 418 Deaths at 9 mg/kg/day. NOEL 0.3 mg/kg/day. 95.0170 (Mar Previously N/A [C24 h (µg/mL) data: As above, and additional toxicity 1995); GLP evaluated 4 week associated with Baccilus piliformis 1.5; 1.2; 1.8] ≤ IV study in Wistar infection, and one case of CNS rats; haemorrhage (not associated with infection). Deaths at all doses 0, 3.2, 8, 20 (attributed to hepatic disease). NOEL not established.
mg/kg/day. NOAEL 1 mg/kg/day. No neoplastic findings. Rat M / F 017716 (Jun 1999); GLP; day 30 kinetic data 3 months PO in Wistar rats; 0, 0.5, 1, 4 2.4 / 2.8 4.7 / 5.7 17 / 21 35 / 38 71 / 70 217 / 202 Red blood cell parameters (marginal ↓), liver (marginal ↑ in weight) at HD. NOAEL 4 mg/kg/day. 2003-1492 (Sep 2005); GLP; day 181 kinetic data 6 months PO in SD rats; 0, 0.3, 1.5 (↑ to 9 at week 15), 3, 6 1.5 / 1.8 8.6 / 9.4 (day 90) and 40 / 49 20 / 21 33 / 33 26 / 29 102 / 124 (day 90) and 487 / 568 240 / 330 342 / 418 Atrophic changes in haematopoietic tissues/organs, spleen; lymphoid tissues/organs; intestinal tract and reproductive tissues; liver (hepatocyte focal and (mainly at fatal doses) single cell necrosis). Deaths at 9 mg/kg/day. NOEL 0.3 mg/kg/day. 95.0170 (Mar 1995); GLP Previously evaluated 4 week IV study in Wistar rats; 0, 3.2, 8, 20 N/A [C24 h (µg/mL) data: 1.5; 1.2; ≤ 1.8] As above, and additional toxicity associated with Baccilus piliformis infection, and one case of CNS haemorrhage (not associated with infection). Deaths at all doses (attributed to hepatic disease). NOEL not established.
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