Learning behavior in rat offspring after in utero and lactational exposure to either TCDD or PCB126

<p><b>OBJECTIVES</b>We studied and compared the possible effects of in utero and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) on learning behavior in offspring.</p><p><b>METHODS</b>Pregnant Long-Evans Hooded rats were administered either TCDD (50, 200, or 800 ng/kg) or PCB126 (500, 2,000 or 8,000 ng/kg) on gestational day 15. A procedure of schedule-controlled operant behavior was applied to examine learning behavior in the male and female offspring at 11 weeks of age for 30 days. Three indices, namely, response rates in a fixed ratio (FR) and in a differential reinforcement of low rates (DRL), and reward rate in the DRL component in multiple FR 20 DRL 20 s (mult-FR 20 DRL 20-s) test sessions, were used for the evaluation of learning behavior.</p><p><b>RESULTS</b>Toxic effects on learning behavior in male and female pups following in utero and lactational exposure to TCDD or PCB126 were observed mainly in the FR learning component. However, no linear dose-dependent effects of either of the two compounds were observed for the above three indices. The response rates of animals in the low-dose TCDD and PCB126 groups decreased and those in medium-dose TCDD and PCB126 groups appeared to induce hyperactive behavior. The high dose of PCB126 appeared to have a distinct toxicity from that of TCDD in terms of the acquisition of learning behavior.</p><p><b>CONCLUSIONS</b>Toxicities of PCB126 and TCDD in learning behavior might be similar to each other and the current toxic equivalency factor (TEF) of 0.1 for PCB126 can be considered to be appropriate for this endpoint.</p>

Determination of Dioxins in Human Hair: Estimation of External and Internal Exposure to Dioxins

Objectives: To clarify the origin of dioxin and related compounds (dioxins) in human hair, we determined the amounts of adsorbed dioxins in human hair, and the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats. Methods: Human hair specimens, packed in a glass column, were exposed to ambient air that was introduced into the column with an air pump for 24 h. Rats were administered TCDD by gavage at doses of 0.2, 0.8, and 1.6 μg/kg body weight. Four weeks after TCDD administration, hair from the back, serum, and adipose tissue were removed under diethyl ether anesthesia. The amounts of dioxins in these samples were analyzed by high resolution gas chromatography with mass spectroscopy. Results: Exposure of the hair specimens to ambient air for one day increased the total toxic equivalent (TEQ) value by 51%. In TCDD-treated rats, the amount of TCDD in hair increased in a dose-dependent manner, and showed a significant positive correlation with that in adipose tissue. Conclusions: Human hair was found to retain dioxins by both internal and external exposure, and the contribution of external exposure was estimated to be about 40% of the TEQ.

Maternal Exposure to 2,3,7,8-Tetrachlorodibenzo-\it{p}-Dioxin and the Body Burden in Offspring of Long-Evans Rats

Objectives: In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams and fetuses and developmental effects on pups. Materials and Methods: Pregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [3H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16 and GD21, and the tissue concentrations of TCDD were measured in dams and fetuses. Pups were sacrificed on postnatal day (PND) 49 and PND63 for males and PND70 for females, and the reproductive effects and tissue concentrations of TCDD were determined. Results: The sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg and at 12.5 and 50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg and in males and females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility, and ejaculated sperm count were not affected. Estrous cyclicity was not different from that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle and prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden and TCDD concentration in fetuses were 290 pg TCDD/g and 52 pg TCDD/g on GD16, respectively. Reduced prostate weight is a sensitive and commonly observed endpoint so that the body burdens of dams and fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the body burden in offspring of long-evans rats

<p><b>OBJECTIVES</b>In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams and fetuses and developmental effects on pups.</p><p><b>MATERIALS AND METHODS</b>Pregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [(3)H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16 and GD21, and the tissue concentrations of TCDD were measured in dams and fetuses. Pups were sacrificed on postnatal day (PND) 49 and PND63 for males and PND70 for females, and the reproductive effects and tissue concentrations of TCDD were determined.</p><p><b>RESULTS</b>The sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg and at 12.5 and 50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg and in males and females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility, and ejaculated sperm count were not affected. Estrous cyclicity was not different from that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle and prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden and TCDD concentration in fetuses were 290 pg TCDD/g and 52 pg TCDD/g on GD16, respectively. Reduced prostate weight is a sensitive and commonly observed endpoint so that the body burdens of dams and fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.</p>

Determination of dioxins in human hair: Estimation of external and internal exposure to dioxins

<p><b>OBJECTIVES</b>To clarify the origin of dioxin and related compounds (dioxins) in human hair, we determined the amounts of adsorbed dioxins in human hair, and the distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats.</p><p><b>METHODS</b>Human hair specimens, packed in a glass column, were exposed to ambient air that was introduced into the column with an air pump for 24 h. Rats were administered TCDD by gavage at doses of 0.2, 0.8, and 1.6 μg/kg body weight. Four weeks after TCDD administration, hair from the back, serum, and adipose tissue were removed under diethyl ether anesthesia. The amounts of dioxins in these samples were analyzed by high resolution gas chromatography with mass spectroscopy.</p><p><b>RESULTS</b>Exposure of the hair specimens to ambient air for one day increased the total toxic equivalent (TEQ) value by 51%. In TCDD-treated rats, the amount of TCDD in hair increased in a dose-dependent manner, and showed a significant positive correlation with that in adipose tissue.</p><p><b>CONCLUSIONS</b>Human hair was found to retain dioxins by both internal and external exposure, and the contribution of external exposure was estimated to be about 40% of the TEQ.</p>