Necropsy Changes observed at the end of treatment period : From low dose ( 5 mg / kg COMPOUND_XXX ) and higher : e â € " Cysts ( mainly bilateral ) in the ovaries of single animals of group 2 and 3 e Diminished size of uterine horns , cervix and uterus body e Increased incidence and severity of ovarian follicular cysts Â ¢ Atrophy of uterine horn , body and cervix in most animals Findings from the mid dose of 15 mg / kg COMPOUND_XXX and higher : e Increased incidence and severity of focal / multifocal foam cell aggregates in all animals of group 3 Additional findings at the high dose ( 50 mg / kg COMPOUND_XXX ) : e Emaciation of single animals e â € " Gray - white foci in all lobes of the lungs in single animals e Diminished size of ovaries , thymus and iliac lymph nodes in single animals e Diffuse adrenocortical atrophy and associated lipid depletion e Diffuse hepatocellular hypertrophy e Vacuolation of Kupffer cells e Diffuse alveolar foam cell ( i.e. histiocytes ) aggregation ( with associated acute / mixed inflammation and hyperplasia of alveolar type II pneumocytes ) e Accumulation of multinucleated giant cells in the BALT of single animals e Hypocellularity of the femoral and sternal bone marrow and associated congestion in most rats e Lobuloalveolar histologic pattern in the mammary gland .
Necropsy Changes observed at the end of treatment period : From low dose ( 5 mg / kg COMPOUND_XXX ) and higher : e â € " Cysts ( mainly bilateral ) in the ovaries of single animals of group 2 and 3 e Diminished size of uterine horns , cervix and uterus body e Increased incidence and severity of ovarian follicular cysts Â ¢ Atrophy of uterine horn , body and cervix in most animals Findings from the mid dose of 15 mg / kg COMPOUND_XXX and higher : e Increased incidence and severity of focal / multifocal foam cell aggregates in all animals of group 3 Additional findings at the high dose ( 50 mg / kg COMPOUND_XXX ) : e Emaciation of single animals e â € " Gray - white foci in all lobes of the lungs in single animals e Diminished size of ovaries , thymus and iliac lymph nodes in single animals e Diffuse adrenocortical atrophy and associated lipid depletion e Diffuse hepatocellular hypertrophy e Vacuolation of Kupffer cells e Diffuse alveolar foam cell ( i.e. histiocytes ) aggregation ( with associated acute / mixed inflammation and hyperplasia of alveolar type II pneumocytes ) e Accumulation of multinucleated giant cells in the BALT of single animals e Hypocellularity of the femoral and sternal bone marrow and associated congestion in most rats e Lobuloalveolar histologic pattern in the mammary gland .
O O O O O O O O O O O B-DOSE_QUALIFICATION I-DOSE_QUALIFICATION O B-DOSE I-DOSE I-DOSE I-DOSE O O O O O O O O O B-FINDING O O O O O O B-SPECIMEN O O O O B-GROUP I-GROUP I-GROUP I-GROUP O B-FINDING I-FINDING O B-SPECIMEN I-SPECIMEN O B-SPECIMEN O B-SPECIMEN I-SPECIMEN O B-MANIFESTATION_FINDING O O O O B-SPECIMEN B-FINDING I-FINDING O O B-FINDING O B-SPECIMEN I-SPECIMEN O B-SPECIMEN O B-SPECIMEN O O O O O O B-DOSE_QUALIFICATION I-DOSE_QUALIFICATION O B-DOSE I-DOSE I-DOSE I-DOSE O O O O O B-MANIFESTATION_FINDING O O O O B-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING O O O O B-GROUP I-GROUP O O O O B-DOSE_QUALIFICATION I-DOSE_QUALIFICATION O B-DOSE I-DOSE I-DOSE I-DOSE O O O O B-FINDING O O O O O O O B-FINDING I-FINDING I-FINDING I-FINDING O O O O O B-SPECIMEN O O O O B-FINDING I-FINDING O B-SPECIMEN I-SPECIMEN B-SPECIMEN O B-SPECIMEN I-SPECIMEN I-SPECIMEN O O O O B-FINDING I-FINDING I-FINDING O O B-FINDING I-FINDING O B-FINDING I-FINDING I-FINDING O B-FINDING I-FINDING I-FINDING I-FINDING O B-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING O O O B-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING I-FINDING O O B-FINDING O B-FINDING I-FINDING I-FINDING O O B-SPECIMEN O O O O B-FINDING O O B-SPECIMEN O B-SPECIMEN I-SPECIMEN I-SPECIMEN O O B-FINDING O O O O B-FINDING I-FINDING I-FINDING O O B-SPECIMEN I-SPECIMEN O