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ABSTRACT: The objective of this study is to develop a gametogenesis protocol to serve as a model for evaluating the toxic effects of chemicals on oogenesis and spermatogenesis in the eastern oyster (Crassostrea virginica). The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) was selected as a "proof of principle" toxicant to examine developmental toxicity in this invertebrate system. The studies were designed to: (1) test the model using 2,3,7,8-TCDD and (2) to use histopathological evaluations to characterize the effects on oocyte and sperm development during stages of gametogenesis. 2,3,7,8-TCDD at 10 pg/g resulted in significant histopathological gonadal lesions by day 14 of gametogenesis in both female and male oysters. These lesions resulted in complete inhibition of gonadogenesis. Studies also showed that a total body dose of 2 and 10 pg/g 2,3,7,8-TCDD caused adverse responses resulting in abnormal gametogenesis in female and male oysters, respectively, such as: (1) incomplete oocyte division, (2) inhibition of oocyte growth and maturation, (3) unsynchronized sperm development, and (4) inhibition of spermatogenesis. The eastern oyster is one of the most responsive invertebrate models tested to date for reproductive effects of chemicals. Therefore, the eastern oyster can be used as a sensitive toxicological model for examining the effects of dioxin-like compounds and other xenobiotics on gametogenesis. The reported studies show that environmentally relevant concentrations of 2,3,7,8-TCDD (2-10 pg/g) have a significant adverse effect on oyster gametogenesis.
Aquatic Toxicology 03/2007; 81(1):10-26. · 3.76 Impact Factor
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ABSTRACT: Reproductive and developmental effects of diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were evaluated in a Japanese medaka (Oryzias latipes) multigeneration protocol. Each phthalate was administered via fish flake diets at a concentration of 20 microg/g (1 microg/g fish/day). Two controls were included, untreated and acetone carrier. The F(0) and F(1) generation adults were reared to sexual maturation and the test was ended prior to sexual maturation of the F(2) generation. Biochemical, individual, and population parameters were evaluated: testosterone metabolism, 7-ethoxyresorufin-o-deethylase (EROD) activity, survival, development, growth, gonadal-somatic index, histopathology, sex ratio, and fecundity. Male fish showed a two-fold induction of several testosterone metabolites in the DINP-treated group compared to the untreated control but not the acetone control. In a similar manner, in female fish only the DIDP-treated group expressed greater testosterone hydroxylase activity. There were neither sex- nor treatment-related differences in the results from the EROD assay. A statistically significant transient delay in red blood cell pigmentation was observed. The male-to-female ratio was consistent across treatments and the phenotypic and histological gender classifications were in agreement. Egg production was not significantly different among treatment groups. Neither phthalate elicited an effect on reproduction or development at various levels of biological organization.
Ecotoxicology and Environmental Safety 10/2006; 65(1):36-47. · 2.29 Impact Factor
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ABSTRACT: We determined the inducibility, as well as the persistence of the induction, of hepatic microsomal CYP1A1 and CYP1A2 (by western blot analysis), and their catalytic activities (as measured by resorufin ether O-dealkylation) in prepubertal (25-day-old) and adult (120-day-old) offspring of timed-pregnant Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment was subcutaneous, at a low dose of 0.1 microg/kg, on gestational days 7, 14, and 20, and on lactational days 7 and 14. CYP1A1 protein was induced significantly (23-fold) in prepubertal but not in adult offspring of TCDD-exposed dams, whereas ethoxyresorufin O-deethylase (EROD) activity, which is CYP1A1-preferential, was induced less extensively (5-fold) and slightly (1.7-fold) in the prepubertal and adult offspring, respectively. Benzyloxyresorufin O-debenzylase (BROD) activity, which is CYP2B-preferential but has been reported to be catalyzed by CYP1A1, was also induced 5- and 6-fold in prepubertal and adult offspring, respectively, of TCDD-exposed dams. However, the induced BROD activity was neither inhibited by antibody against CYP1A1 nor accompanied by an elevated level of microsomal CYP2B. CYP1A2 was induced slightly only in prepubertal offspring of TCDD-treated dams. There was suggestive evidence of enhanced lipid peroxidation in hepatic microsomes from prepubertal but not adult offspring of TCDD-treated dams. These data showed that in utero plus lactational TCDD exposure effected transient induction of hepatic microsomal CYP1A1 but sustained induction of BROD activity, which may be catalyzed by enzymes other than CYP1A or CYP2B.
Biochemical Pharmacology 06/2000; 59(9):1147-54. · 4.70 Impact Factor
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ABSTRACT: Definitive data on reproductive impairment of chronically exposed populations may be required to assess the appropriateness of the existing test methods for hazard identification and prioritization of endocrine modulators. Multigeneration toxicity testing protocols for wildlife receptors are lacking. To help address this gap we describe a multigeneration fish assay using the freshwater fish, Japanese medake (Oryzias latipes). This test species has been used for the evaluation of carcinogenic, teratogenic and reproductive effects and is sensitive to estrogen exposure producing ovo-testis, altered biochemical parameters and phenotypic characteristics. Due to the short life cycle, a multigeneration test with medaka can be conducted in 1 year. Endpoints evaluated include: survival, growth, sex ratio, fecundity, embryonic lesion occurrence, embryonic stage development, gonadal and hepatic somatic indices, histopathology and biochemical parameters. As new endpoints are developed they can be incorporated into the protocol. Results of a positive control (17 beta-estradiol) study are presented to give an indication of the baseline associated with various test endpoints and to highlight the importance of nutrition in the experimental design. 17 beta-Estradiol treatment induced vitellogenin production in male and female medaka, feminized males, and disrupted egg production. The proposed protocol provides researchers with an effective multigeneration fish test that can be used to examine potential effects of stressors at the population, individual, cellular and subcellular level.
Science of The Total Environment 09/1999; 233(1-3):211-20. · 3.29 Impact Factor
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ABSTRACT: Polychlorinated biphenyls (PCBs) are widespread environmental contaminants which can biomagnify to higher tropic level organisms including birds. Circulating thyroid hormones (TH) and growth are decreased by PCB exposure. The first set of studies investigated the effects of PCBs on an enzyme responsible for TH homeostasis, hepatic type I monodeiodinase (MDI) in chicken embryos. Fertile chicken eggs were injected with Aroclor 1242, Aroclor 1254, 2,2',6, 6'-tetrachlorobiphenyl (TCB), 3,3',4,4'-TCB, or 3,3',5,5'-TCB on Day 0 and studies were terminated on Incubation Day 21. Hepatic MDI activity was reduced in embryos treated with the Aroclor mixtures. No effects on MDI activities were observed after PCB isomer treatment. Liver weights from embryos treated with Aroclor 1242 were decreased. In the second study, chick embryos were exposed to these same PCBs in order to evaluate their effect on circulating THs and growth. Treatment with PCBs had no effect on body weight. Femur length were decreased with Arcolor 1242 treatment. A decrease in plasma concentration of thyroxine was observed after treatment with Aroclor 1242 and Aroclor 1254. Based on these findings, it is evident that PCBs alter the thyroid axis. Bird circulating TH levels, which are generally reported, may not be a good biomarker for low-dose exposure to PCBs. However, the reduction in MDI activity was more sensitive to PCB mixture exposure and may be a useful biomarker.
Ecotoxicology and Environmental Safety 07/1999; 43(2):195-203. · 2.29 Impact Factor
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ABSTRACT: Polychlorinated biphenyls (PCB) are ubiquitous environmental contaminants that bioaccumulate in avian species. Exposure to PCBs can result in decreased growth. Thyroid hormones and growth hormone (GH) are important for normal growth. The present studies employed the chicken embryo to investigate effects of Aroclor 1242, Aroclor 1254, 2,2',6,6'-tetrachlorobiphenyl (TCB), 3,3',4,4'-TCB, and 3,3',5,5'-TCB on growth and growth-related hormones. The following indices were measured: embryo mortality, body weights, bone length, pituitary GH content, and plasma concentrations of triiodothyronine (T3), thyroxine (T4), GH, and insulin-like growth factor-1 (IGF-1). Fertile eggs were injected with PCBs on Day 0 and indices determined on Day 17 of incubation. Unexpectedly, 3,3',5,5'-TCB or low-dose Aroclor 1242 treatment increased body weight and bone length (P < 0.05), whereas Aroclor 1242 (high dose), 3,3,4,4'-TCB, or Aroclor 1254 treatment reduced body weights and/or bone length (P < 0.05). Aroclor 1242 or 3,3',4,4'-TCB (low-dose treatment) elevated plasma T4 concentrations (P < 0.05). Both growth and pituitary GH content were increased (P < 0.05) by 3,3',5,5'-TCB (low dose) or Aroclor 1242 treatment. Despite marked differences in growth rates, plasma T3, GH, and IGF-I concentrations were unaffected by PCB treatment. Growth-related hormones may not be responsible for the growth depression observed after PCB treatment. Possibly the decrease in growth occurred because of general toxicity. The importance of chlorine position in causing thyroid hormone axis alterations was not clearly established.
General and Comparative Endocrinology 05/1997; 106(2):221-30. · 3.27 Impact Factor
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Bulletin of Environmental Contamination and Toxicology 08/1996; 57(1):84-90. · 1.02 Impact Factor
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ABSTRACT: Using radioiron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that benzene inhibited bone marrow function in female mice. Hydroquinone was marginally effective, but the inhibition occurred only at the highest dose tested (100 mg/kg). The combination of phenol and hydroquinone was more effective in reducing erythrocyte production than either chemical given alone. Catechol given alone was not inhibitory but when phenol was added to catechol, erythropoiesis was suppressed, as observed for the phenol and hydroquinone combination. It appears that benzene toxicity may be the result of cooperative inhibitory effects produced by its metabolites.
Chemico-Biological Interactions 02/1990; 74(1-2):55-62. · 2.46 Impact Factor
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ABSTRACT: Monochloroacetic acid (MCA) causes front paw rigidity in 10% of mice surviving a single oral toxic dose (320-380 mg/kg). Mice exhibiting front paw rigidity were killed at various times after MCA treatment and their brains were prepared for histological examination. As early as 48 hr post-treatment, RBCs were found outside capillaries in several brain regions, especially the cerebellum. At time points up to 8 weeks after MCA, extracapillary RBCs were seen to be undergoing lysis, and there was loss of cerebellar Purkinje cells. Three hours after oral administration of an LD80 of MCA (380 mg/kg), entry of iv-injected [14C]inulin or [3H]dopamine (1.0 microCi) into all brain regions was significantly increased compared to controls. Increased entry of [14C]inulin into the brains of mice occurred as early as 2 hr after MCA, coinciding with the onset of signs of toxicity, and remained elevated for up to 8 hr following treatment. Further studies revealed that only those mice which were moribund but not those which were unaffected by MCA (380 mg/kg) 4-6 hr after treatment had significantly increased brain levels of [14C]inulin or [3H]dopamine. However, mice which survived an LD80 of MCA and exhibited front paw rigidity 24 hr later also had brain radiotracer concentrations significantly greater than controls. Both the lethal effects of MCA and the physical deficits observed in survivors may be associated with impairment of blood-brain barrier function.
Fundamental and Applied Toxicology 11/1987; 9(3):469-79.
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ABSTRACT: A physiologically based pharmacokinetic model for the uptake, distribution and excretion of 2,3,7,8-tetrachloro-p-dioxin in the commercially important bivalve Mya arenaria is described. Exposure to dioxins in this filter-feeding bivalve takes place through the gills, digestive gland and direct contact of filtered ambient water with the mantle and outer surface of the gonads. Excretion of the absorbed dioxins occurs through the equilibration of the hemolymph and the filtered water in the gills, diffusion outflow from the exposed body surfaces to ambient water, urine, feces, spawning and diapedesis of macrophages. Biodegradation of the planar dioxin isomers has been considered negligible for this organism. The homogeneous compartments used in the model are mantle, digestive gland, kidney, gonads and muscle. Experimental data collected in order to determine the different parameters necessary to run the model include the lipid content and hemolymph flow to different organs. The model predictions have been tested using our experimental results on the distribution of radiolabeled dioxin in M. arenaria.
Marine Environmental Research. 34:321-325.
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ABSTRACT: The objective of this study is to develop a gametogenesis protocol to serve as a model for evaluating the toxic effects of chemicals on oogenesis and spermatogenesis in the eastern oyster (Crassostrea virginica). The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) was selected as a “proof of principle” toxicant to examine developmental toxicity in this invertebrate system. The studies were designed to: (1) test the model using 2,3,7,8-TCDD and (2) to use histopathological evaluations to characterize the effects on oocyte and sperm development during stages of gametogenesis. 2,3,7,8-TCDD at 10 pg/g resulted in significant histopathological gonadal lesions by day 14 of gametogenesis in both female and male oysters. These lesions resulted in complete inhibition of gonadogenesis. Studies also showed that a total body dose of 2 and 10 pg/g 2,3,7,8-TCDD caused adverse responses resulting in abnormal gametogenesis in female and male oysters, respectively, such as: (1) incomplete oocyte division, (2) inhibition of oocyte growth and maturation, (3) unsynchronized sperm development, and (4) inhibition of spermatogenesis. The eastern oyster is one of the most responsive invertebrate models tested to date for reproductive effects of chemicals. Therefore, the eastern oyster can be used as a sensitive toxicological model for examining the effects of dioxin-like compounds and other xenobiotics on gametogenesis. The reported studies show that environmentally relevant concentrations of 2,3,7,8-TCDD (2–10 pg/g) have a significant adverse effect on oyster gametogenesis.
Aquatic Toxicology.
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[show abstract]
[hide abstract]
ABSTRACT: Reproductive and developmental effects of diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were evaluated in a Japanese medaka (Oryzias latipes) multigeneration protocol. Each phthalate was administered via fish flake diets at a concentration of 20 μg/g (1 μg/g fish/day). Two controls were included, untreated and acetone carrier. The F0 and F1 generation adults were reared to sexual maturation and the test was ended prior to sexual maturation of the F2 generation. Biochemical, individual, and population parameters were evaluated: testosterone metabolism, 7-ethoxyresorufin-o-deethylase (EROD) activity, survival, development, growth, gonadal–somatic index, histopathology, sex ratio, and fecundity. Male fish showed a two-fold induction of several testosterone metabolites in the DINP-treated group compared to the untreated control but not the acetone control. In a similar manner, in female fish only the DIDP-treated group expressed greater testosterone hydroxylase activity. There were neither sex- nor treatment-related differences in the results from the EROD assay. A statistically significant transient delay in red blood cell pigmentation was observed. The male-to-female ratio was consistent across treatments and the phenotypic and histological gender classifications were in agreement. Egg production was not significantly different among treatment groups. Neither phthalate elicited an effect on reproduction or development at various levels of biological organization.
Ecotoxicology and Environmental Safety.
