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

“Tapinarof was not mutagenic or clastogenic in the Ames bacterial reverse mutation assay, the in vitro mammalian chromosome aberration test, and the in vitro mouse lymphoma assay. Tapinarof was not genotoxic in two in vivo micronucleus assays in mice and rats.”

“No drug-related neoplasms were noted in mice after 98 (females) to 102 (males) weeks of daily topical administration at doses up to 3% tapinarof cream (44 times the MRHD based on AUC comparisons). No drug-related neoplasms were noted in female rats after 83 weeks of daily subcutaneous administration at doses up to 1 mg/kg/day tapinarof (9 times the MRHD based on AUC comparisons).”

“There were test article-related decreases in F1 pup survival and viability at ≥6 mg/kg/day that resulted in reduced litter sizes and decreased pup weights. The NOAEL was 1 mg/kg/day for tapinarof effects on prenatal and postnatal development of the offspring in rats.”

“Tapinarof inhibited hERG channel tail current in a concentration-dependent manner. The IC25, IC50 and IC75 values were estimated to be 1.72, 4.02, and 9.37 μM, respectively.”

“Tapinarof was not mutagenic or clastogenic in the Ames bacterial reverse mutation assay, the in vitro mammalian chromosome aberration test, and the in vitro mouse lymphoma assay. Tapinarof was not genotoxic in two in vivo micronucleus assays in mice and rats.”

“Tapinarof was not mutagenic or clastogenic in the Ames bacterial reverse mutation assay, the in vitro mammalian chromosome aberration test, and the in vitro mouse lymphoma assay. Tapinarof was not genotoxic in two in vivo micronucleus assays in mice and rats.”

“Tapinarof was not mutagenic or clastogenic in the Ames bacterial reverse mutation assay, the in vitro mammalian chromosome aberration test, and the in vitro mouse lymphoma assay. Tapinarof was not genotoxic in two in vivo micronucleus assays in mice and rats.”

“The subcutaneous carcinogenicity study in Wistar-Han rats is negative for drug-related neoplasms in female rats but the male portion of the study, while it did not show any statistical increase in tumors, was of an inadequate duration.”

“Long-term carcinogenicity studies were conducted in mice (daily topical administration at doses of 0.5, 1.5 and 3% tapinarof cream) and in rats (subcutaneous administration at doses of 0.1, 0.3, and 1 mg/kg/day tapinarof).”

“Tapinarof inhibited hERG channel tail current in a concentration-dependent manner. The IC25, IC50 and IC75 values were estimated to be 1.72, 4.02, and 9.37 μM, respectively.”