TABLE 7.

Toxicological Findings in Rats and Dogs After Single (“Expanded”) and Repeated IV Administrations of Gadopiclenol

Species	Duration of Treatment	Dose Level, mmol/kg	Findings	Reversibility
Rat	1 d	0, 2.5, 5, 10	• At 10 mmol/kg (1 M), swelling of the limbs	Reversible
			• At 10 mmol/kg (M), increase in kidney weights and epithelial tubular cells vacuolation	Partially reversible
Rat	14 d	0, 2.5, 5, 10	• Dose-related decrease in body weight gain and food consumption	Partially reversible
			• Dose-related decreases in RBC, hematocrit, hemoglobin, and triglyceride levels	Reversible
			• Mild to severe tubular cell vacuolations in the renal cortex and urinary bladder	Partially reversible
			• At 5 and/or 10 mmol/kg per d, cell vacuolation findings present in liver, lungs, lymph nodes, and in tissues throughout the body, mainly as vacuolated/granular macrophages	Reversible
Rat	28 d	0, 2.5, 5, 10	• At highest dose level, swelling of the limbs and/or nose/muzzle, decreased activity, salivation, urination, and purple discoloration of the tail	Reversible
			• Dose-related decreases in RBC, hematocrit, hemoglobin, and triglyceride levels	Reversible
			• Minimal decreases in ALT in both sexes at high-dose level	Nonreversible
			• Mild to severe tubular cell vacuolations in the renal cortex and urinary bladder	Partially reversible
			• At 5 and/or 10 mmol/kg per d, cell vacuolation findings present in liver, lungs, lymph nodes, and in tissues throughout the body, mainly as vacuolated/granular macrophages	Reversible
Dog	1 d	0, 1, 2, 4	• At 4 mmol/kg (2 M), with peripapillary conus or swelling of the optic nerve	Reversible
			• Dose-dependent vacuolation of epithelial tubular cells	Reversible
Dog	14 d	0, 1, 2, 4	• At all tested doses, increase in kidney weight	Reversible
			• At all dose levels, mild to marked epithelial cell vacuolation of the cortical and medullary tubules	Reversible
Dog	28 d	0, 1, 2, 4	• At the highest dose, swelling of the face and ears during week 2 through 4 (1 M)	Reversible
			• Tan discoloration of kidneys at the high-dose (2 M and 1 F)	Reversible
			• At all tested doses, kidney weight increase	Reversible
			• At all dose levels, mild to marked epithelial cell vacuolation of the cortical and medullary tubules	Reversible
			• Minimal vacuolation in urinary bladder	Reversible

Note: The corresponding NOEL among the tested dose levels is highlighted. The corresponding NOAEL among the tested dose levels is indicated in bold and underlined.

IV, intravenous; ALT, alanine aminotransferase; F, female; M, male; RBC, red blood cell; NOEL, no-observed-effect level; NOAEL, no-observed-adverse-effect level.