Accrufer: genotox, carcinogenicity and repro: done or skipped?

“Ferric maltol was mutagenic in vitro in bacterial reverse mutation (Ames) assays. Ferric maltol increased revertant frequency in the absence and presence of metabolic activation. Fertility studies have not been conducted with ferric maltol. Maltol was mutagenic in the Ames assay and increased micronuclei in an in vivo clastogenicity assay in mice.”

“Maltol was not carcinogenic in a 18-month study in mice at doses up to 400 mg/kg (approximately 5.6 times the human daily dose). Maltol was not carcinogenic in a 2-year study in rats at doses up to 400 mg/kg (approximately 11.2 times the human daily dose).”

“In a multi-generation animal reproduction study in male and female rats, there were no effects on mating, fertility, or early embryonic development at doses up to 400 mg/kg/day (approximately 11.2 times the human daily dose).”

“No standalone safety pharmacology studies were conducted for ferric maltol, which is scientifically justified as the active moiety is iron.”

“Ferric maltol was mutagenic in vitro in bacterial reverse mutation (Ames) assays. Ferric maltol increased revertant frequency in the absence and presence of metabolic activation.”

“Maltol was clastogenic in vivo in a mouse micronucleus assay (increase in polychromatic erythrocytes) at intraperitoneal doses of 774 mg/kg.”

“Maltol was not carcinogenic in an 18-month study in mice at doses up to 400 mg/kg (approximately 5 times the human daily dose). Maltol was also not carcinogenic in a 2-year study in rats at doses up to 400 mg/kg (approximately 10 times the human daily dose).”

“The NDA contains a study report for a mouse 18-month carcinogenicity study of maltol at doses of 0, 100, 200 or 400 mg/kg/day by dietary administration (Report 75009).”

“No standalone safety pharmacology studies were conducted for ferric maltol, which is scientifically justified as the active moiety is iron.”