95.0288 (May Second previously N/A [Mean concentration Deaths in HD rats (changes as 1995); GLP evaluated 4 week 1.1-5.1 µg/mL at described including cerebellar IV trial in Wistar various time-points haemorrhage; attributed to Baccilus rats; 0, 0.25, 1 over 0.5-24 h] piliformis infection). No effects in rats surviving the HD. NOEL 0.25 mg/kg/day. (Sep 2 year PO 3 / 4 51 / 60 Bone marrow (hypocellularity, 2009); GLP; day (carcinogenicity decrease in hematopoietic cells), 9 / 11 104 / 148 169 kinetic data in SD rats; submandibular lymph node 20 / 27 275 / 329 (decreased plasmacytosis), spleen 0, 0.5, 1.5, 4 (decreased lymphocytes and increased pigment (hemosiderin), liver (↑ focus of cellular alteration, hypertrophy, multinucleated hepatocytes). Mortality at MD and ↑ HD (♂ only). NOEL not established. Dog (beagle) M / F 017737 (Jul 3 month PO; 6.4 / 6.7 107 / 118 Atrophic changes in haematopoietic 1999); GLP; day tissues/organs, spleen; intestinal 0, 0.8, 2.5, 8 51 / 34 680 / 590 88 kinetic data tract and oral mucosae; and ↑ 103 / 72 (day 23) 1673 / 1185 (day 23) siderin storage in liver Kupffer cells. Deaths at HD. NOEL 0.8 mg/kg/day.
95.0288 (May 1995); GLP Second previously evaluated 4 week IV in Wistar rats; 0, 0.25, 1 N/A [Mean concentration 1.1-5.1 µg/mL at various time-points over 0.5-24 h] Deaths in HD rats (changes as described including cerebellar haemorrhage; attributed to Baccilus piliformis infection). No effects in rats surviving the HD. NOEL 0.25 mg/kg/day. (Sep 2009); GLP; day 169 kinetic data 2 year PO (carcinogenicity in SD rats; 0, 0.5, 1.5, 4 3 / 4 9 / 11 20 / 27 51 / 60 104 / 148 275 / 329 Bone marrow (hypocellularity, decrease in hematopoietic cells), submandibular lymph node (decreased plasmacytosis), spleen (decreased lymphocytes and increased pigment (hemosiderin), liver (↑ focus of cellular alteration, hypertrophy, multinucleated hepatocytes). Mortality ↑ at MD and HD (♂ only). NOEL not established. Dog (beagle) M / F 017737 (Jul 1999); GLP; day 88 kinetic data 3 month PO; 0, 0.8, 2.5, 8 6.4 / 6.7 51 / 34 103 / 72 (day 23) 107 / 118 680 / 590 1673 / 1185 (day 23) Atrophic changes in haematopoietic tissues/organs, spleen; intestinal tract and oral mucosae; and ↑ siderin storage in liver Kupffer cells. Deaths at HD. NOEL 0.8 mg/kg/day. trial
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