An embryo-fetal development study performed in rats with oral telotristat ethyl at doses up to 750 mg/kg/day (approximately 9 times the AUC area under the plasma concentration-time curve for the active metabolite at the RHD) during organogenesis produced no harm to embryo-fetal development.^L43342

In pregnant rabbits treated orally with telotristat ethyl during organogenesis, an increased incidence of post-implantation loss at doses of 250 and 500 mg/kg/day (approximately 15 times the AUC for the active metabolite at RHD) and a decrease in fetal weight at 500 mg/kg/day (approximately 33 times the AUC for the active metabolite at the RHD) was observed. The adverse effects on embryo-fetal development were associated with maternal toxicity (impaired weight gain and/or mortality) at 250 and 500 mg/kg/day. No adverse effects on embryo-fetal development were observed at 125 mg/kg/day (approximately 5 times the AUC for the active
metabolite at the RHD).^L43342

A pre-/postnatal development study was conducted in rats using oral administration of 100, 200, and 500 mg/kg/day telotristat ethyl during organogenesis through lactation. An increased incidence of pup mortality was observed during postnatal days 0 to 4 at the maternal dose of 500 mg/kg/day (approximately 5 times the AUC for the active metabolite at the RHD). No developmental abnormalities or effects on growth, learning, memory or reproductive performance were observed through the maturation of offspring at maternal doses of up to 500 mg/kg/day in surviving offspring.^L43342

In a 26-week study in transgenic (Tg.rasH2) mice, telotristat ethyl was not tumorigenic at oral doses up to 300 mg/kg/day (approximately 12 to 19 times the AUC for the active metabolite at the RHD).^L43342

In a 2-year carcinogenicity study in Sprague-Dawley rats, telotristat ethyl was not tumorigenic at oral doses up to 170 mg/kg/day (approximately 2 to 5 times the AUC for the active metabolite at the RHD).^L43342

Telotristat ethyl was negative in the in vitro Ames test, the in vitro chromosomal aberration test using Chinese hamster ovary cells, and the in vivo rat micronucleus test.^L43342

Telotristat ethyl at oral doses up to 500 mg/kg/day (approximately 5 times the AUC for the active metabolite at the RHD) was found to have no effect on the fertility and reproductive performance of male or female rats.^L43342