Effects of green tea catechin on embryo/fetal development in rats.

Evidence suggests that the health benefits associated with green tea consumption are related to tea catechins. The objective of this study was to evaluate potential maternal and fetal effects of standardized heat-sterilized green tea catechins (GTC-H). GTC-H was gavage administered to mated female rats from gestation day 6 through 17, at doses of 0, 200, 600, and 2000 mg/kg/day. There were no GTC-H-related deaths or macroscopic findings. During the entire gestation period in the high-dose (2000 mg/kg/day)-treated group and during days 6-9 and 6-18 in the 600 mg/kg/day group, mean body weight gain was lower. Mean feed consumption was lower during gestation days 6-9 in the 600 mg/kg/day group and during gestation days 6-9 and 9-12 in the 2000 mg/kg/day group. Compared to the control group, mean body weights in the 600 and 2000 mg/kg/day groups were up to 5.1% and 7.7% lower during gestation days 9-20. GTC-H administration did not affect mean gravid uterine weights or intrauterine growth and survival. There were no GTC-H-related fetal malformations or developmental variations. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) for GTC-H was 200mg/kg/day for maternal toxicity, and 2000 mg/kg/day for embryo/fetal development.

Safety studies of pseudo-ceramide SLE66. Part 3: Effects on embryo/fetal development in rats.

SLE66 a synthetic pseudo-ceramide, has been shown to reduce dryness/scaling/itching of human skin. Naturally occurring ceramides have been claimed to play a crucial role in cell proliferation, differentiation, and apoptosis including processes important for embryogenesis. The objective of this study was to evaluate the potential maternal and fetal effects of SLE66. SLE66 was administered orally (gavage) to mated female Crl:CD(SD)IGS BR rats (25/group) once daily from gestation day 6 through 19, at dose levels of 0 (control), 150, 400 or 1000 mg/kg/day. No treatment-related clinical or internal (macroscopic) findings were noted and all animals survived to the scheduled necropsy on gestation day 20. SLE66 administration did not affect mean maternal body weights, body weight gains, net body weights, net body weight gains, gravid uterine weights, or feed consumption. Similarly, SLE66 administration did not affect intrauterine growth and survival related parameters such as viable fetuses, pre-implantation loss, early and late resorptions, fetal weight and fetal sex. No SLE66-related fetal malformations or developmental variations were noted. Based on the results of this study, a dose level of 1000 mg/kg/day (highest dose used) was considered as the no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity.

Safety assessment of dietary diacylglycerol oil: a two-generation reproductive toxicity study in rats.

Diacylglycerol (DAG) oil is a novel edible oil with similar taste and usability characteristics as conventional edible oils. Recent studies suggest that DAG oil may be helpful in the prevention and management of obesity. The objective of the present two-generation study was to evaluate potential adverse effects of DAG oil on reproductive processes. DAG oil was administered via gavage to rats (30/sex/group) for at least 70 days prior to mating, at dose levels of 0, 1.25, 2.5 or 5.0 ml/kg/day (0, 1160, 2320 and 4630 mg/kg/day). An additional group received a triacylglycerol (TAG) oil with a similar fatty acid composition to DAG oil. The rats were treated throughout the mating, gestation and lactation periods. Administration of DAG or TAG oil did not reveal any toxicologically significant effects on reproductive performance (mating, fertility and copulation/conception indices). DAG oil did not affect mean gestation lengths, the process of parturition, spermatogenic parameters, organ weights, histopathologic findings, mean numbers of pups born, implantation sites and unaccounted sites. F1 and F2 pup viability, live litter sizes, body weights, mean age of attainment of balanopreputial separation and vaginal patency were similar to those in the control group. Based on the results of this study, a dose level of 5.0 ml/kg (4630 mg/kg/day) was considered as the no-observed-adverse-effect level for reproductive and systemic toxicity, and neonatal toxicity.

Effects of dietary diacylglycerol oil on embryo/fetal development in rats.

Diacylglycerol (DAG) oil is an edible oil with similar taste and usability characteristics as conventional edible oil. Recent studies suggest that use of DAG oil may be helpful in the prevention and management of obesity. This study evaluated the potential maternal and fetal effects of DAG oil, following exposure to pregnant rats, during the critical period of major organogenesis. DAG oil was administered via gavage to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) once daily from gestation day 6 through 17, at dose levels of 0, 1.25, 2.5 or 5.0 ml/kg/day (0, 1160, 2320 and 4630 mg/kg/day) with total volume made to 5 ml/kg/day with triacylglycerol (corn) oil. No mortality or treatment-related clinical or internal findings were noted in any of the groups. Compared to animals in control group, mean maternal body weights, body weight gains, net body weights, net body weight gains, gravid uterine weights, and food consumption were not affected by DAG oil administration. Similarly, intrauterine growth and survival were not affected by DAG oil administration. No DAG oil-related fetal malformations or developmental variations were noted. A maternal maximum tolerated dose for DAG oil was not achieved in this study. Based on the results of this study, a dose level of 5.0 ml/kg (4630 mg/kg/day) was considered as no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity.