For exposure-response array data display purposes, the following results were coded (control and no effect findings were coded as "0", treatment-related increases were coded as "1", and treatment-related decreases were coded as "-1".

p. 7 haematological findings comments

"No change was noted at 10 and 60 mg/kg bw/day in both sexes compared with control. At 300 mg/kg bw/day, 35% decreased reticulocyte count and 25% decreased platelet count was noted in males at the end of the administration compared with control. The effects were not considered to be toxicologically relevant, since there were no histological changes and the changes were only observed in the males. A 40% decreased white blood cell count in females at 300 mg/kg bw/day was noted at the end of the administration compared with control. The effects were not considered to be toxicologically relevant, since there were no histological changes and the changes were only observed in the females. At the end of the recovery period, 8% increased red blood cell and 7% decresased MCV and 7% decresased MCH was noted in females of the 300 mg/kg bw/day group compared with control. See Table 5 under “Any other information on results including tables”. These changes were also not considered to be toxicologically relevant since the changes were not observed at the end of the administration period."

p. 8 Histopathological findings: non-neoplastic

"Changes considered as treatment-related were limited to both sexes at 300 mg/kg bw/day. After the end of the treatment period, centrilobular slight hepatocyte hypertrophy was observed in 2/5 males and 3/5 females in the 300 mg/kg bw/day group. This change may be related to the increased relative liver weight in the male 300 mg/kg bw/day group. The effect is considered to be treatment-related, but adaptive as no changes in the liver was observed in the recovery animals. In the same group, a slight fold of the duodenal mucosa was observed in one male. The relevance of this observation in unclear. In the dead female animal, the following changes were observed: erosion with hemorrhage in the fundic mucosa and erosion of the duodenal mucosa with hypertrophy of the duodenal glands, erosion of cecum, hypertrophy of the cortical cells in the fascicular zone, atrophy of the hematopoietic tissues, and necrosis of lymphocytes in thymus and mandibular lymph node. The erosion effects seen in the GI tract in several animals was related to the corrosive effect of the substance. See Table 8 under “Any other information on results including tables” and Table 4 of the attached study summary."

Male CD(SD) Rat