Placental transport of brevetoxin-3 in CD-1 mice

Abstract

The purpose of this study was to examine the distribution of brevetoxin-3 administered to pregnant dams and to determine the extent of placental transport to fetuses. Twenty-nine pregnant CD-1 mice were administered (3)H-brevetoxin-3 ( approximately 1.3 microCi/animal; approximately 2.8 microg compound/kg) by intratracheal instillation on one of gestational days 15-18. Groups of four or five dams were killed at selected times through 48 h post-dosing. Four pregnant dams were administered (3)H-brevetoxin-3 on gestational day 15 or 16 via osmotic minipump to provide continuous delivery of compound ( approximately 0.13 microCi, 7.5 ng compound/day) over a 72-h period. Then the dams and fetuses were killed. Brevetoxin-associated radioactivity was detected in placentas and fetuses within 0.5h of intratracheal administration. Concentrations of brevetoxin equivalents in fetuses were approximately 0.3 ng/g throughout the 48-h post-dosing, resulting in a calculated dose to fetuses of 19 ng/gh. Following brevetoxin infusion, concentration of brevetoxin equivalents in fetuses was 0.1 ng/g, lower than that present in most maternal tissues. Results demonstrated placental transport of brevetoxin or its metabolites following maternal acute exposure and repeated low-dose exposure. The consequences of these findings for pregnant women exposed to brevetoxins by inhalation or ingestion remain to be determined.

Figure 1

a. Percentages of the administered brevetoxin dose present in selected maternal tissues up to 48 hours post dosing. Results are the means of 4 values except for all tissues at the 24 hour time point, where n = 5. b. Percentages of administered brevetoxin dose in maternal blood, reproductive tissues and fetuses as a function of time after dosing. Results are the means of 4 values except for all tissues at the 24 hour time point, where n = 5 and placentas at 48 hr where n = 2.

Figure 2

Concentrations of brevetoxin equivalents present in maternal blood, reproductive tissues and fetuses as a function of time after dosing. Results are the means of 4 values except for all tissues at the 24 hour time point, where n = 5 and placentas at 48 hr where n = 2.