Transfer and distribution of accumulated (14C)polychlorinated biphenyls from maternal to fetal and suckling rats

Takagi, Yasuhiro; Aburada, Satoshi; Hashimoto, Katsufumi; Kitaura, Toshiyuki

doi:10.1007/bf01054917

Cited by 50 publications

(22 citation statements)

References 22 publications

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“…Total PCB levels in maternal and fetal cord blood were reported to be 2.4 to 3.5 ppm (equivalent to 7 to 12 M) in mothers from Upstate New York (Bush et al, 1984(Bush et al, , 1985. Similar blood concentrations were also reported in animals (offsprings and dams) exposed to PCBs (Takagi et al, 1986;Nims et al, 1994). Specific PCB congeners such as PCBs 138 and 153, which bind to TTR effectively (IC50 ϭ 28 -90 nM), were detected as high as 1-2 ppm (equivalent to 3000 -6000 nM) in the plasma of mothers from industrialized areas in the Netherlands (Koopman- Esseboom et al, 1994a) and in the Aland/Turku Archipelago (Hagmar et al, 1998).…”

Section: Discussionsupporting

confidence: 53%

Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein

Chauhan

Kodavanti

McKinney

2000

Toxicology and Applied Pharmacology

166

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.ortho-Substituted polychlorinated biphenyls (PCBs) make up a large part of the PCB residue found in the environment and human tissues. Our laboratory as well as others have demonstrated that ortho-substituted congeners exhibit important biological activities by aryl hydrocarbon (Ah) receptor-independent mechanisms, including changes in second messenger systems necessary for normal cell function and growth. Previous structure-activity relationship (SAR) studies on second messengers and transthyretin (TTR; prealbumin) binding focused little attention on the ortho-substituted PCBs. Disruption of thyroid hormone (TH) transport is one potentially important mechanism by which PCBs can alter TH homeostasis. A more systematic study of PCB binding to TTR, a major TH transport protein, was undertaken, in which the role of ortho-substitution was more thoroughly investigated. Results from this study indicated that the ortho-only substituted series showed significant binding activity and the relative affinities were 2,2,6 > 2,2 ‫؍‬ 2,6 Ͼ Ͼ 2 ‫؍‬ 2,2,6,6. As anticipated on the basis of steric considerations, bromine was shown to be more active as an ortho-substituent where the relative affinity of 2,2-Br was equivalent to 2,2,6-Cl. The congener patterns (dimeta-substitution in one or both rings) most closely resembling the diiodophenolic ring of thyroxine (T 4 ) showed the highest binding activity. Multiple ortho-substituents were shown to decrease binding activity in such patterns. Congener patterns (single metasubstitution in one or both rings) more closely resembling the monoiodophenolic ring of T 3 showed significantly lower binding activity, consistent with the relatively low binding activity of T 3 and smaller size of chlorine compared to iodine. The addition of ortho-substitution to such patterns gave variable results depending on the substituent relationship (adjacency or nonadjacency) to the pattern. Some patterns such as 2,2,4,4,5,5 showed good binding activity and represent common congeners in the commercial Aroclor mixtures and in the environment. The binding potencies of ortho-PCBs to TTR may represent a signature SAR that predicts specific biologic/toxic effects. In this regard, the binding potencies were consistent with measured biological activities of these PCBs, including effects on cell dopamine content, Ca 2؉ homeostasis, and protein kinase C translocation in neuronal cells and brain homogenate preparations.

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Section: Discussionsupporting

confidence: 53%

Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein

Chauhan

Kodavanti

McKinney

2000

Toxicology and Applied Pharmacology

166

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“…PCBs administered to the dam are not fully transferred to offspring, either during gestation or via lactation, and amounts transferred to each pup are estimated to be approximately 500× less than maternal exposure (Takagi et al, 1986). Therefore, we estimate that our pups were exposed to a maximum of 0.2, 2 and 20 g/kg, in the range of estimated human exposures (Lackmann, 2002;Stellman et al, 1998).…”

Section: Animalsmentioning

confidence: 91%

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Steinberg

Juenger

Gore

2007

Hormones and Behavior

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Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

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“…Based on PCB (U-14 C-labelled KC-600) dynamics in pregnant and nursing rats (Takagi et al 1986), a conservative estimate for TEQ dose in our rat pups was calculated using preliminary measurement of a transfer of 3.2 and 4.9% of the total maternal dose to each rat pup by age 11 and 25 days, respectively, but assuming no loss by mothers via faeces and urine and no metabolic breakdown of contaminants in the pups.…”

Section: Estimation Of Contaminant Intake By Pupsmentioning

confidence: 99%

Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD

Ross¹,

Swart²,

Vliet

et al. 1997

Archives of Toxicology

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While the immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been well established, the eects of complex environmental mixtures of polyhalogenated aromatic hydrocarbons (PHAHs) are poorly understood. Many PHAHs, including the polychlorinated-biphenyls (PCBs), -dibenzofurans (PCDFs), and dibenzo-p-dioxins (PCDDs), possess`dioxin-like' activities, and accumulate in the aquatic food chain. Organisms occupying high trophic levels may therefore be exposed to concentrations which may present an immunotoxic risk. In this study, pregnant PVG rats were administered a daily oral dose of 1 ml of the following during pregnancy and lactation: (1) oil extracted from herring caught in the relatively uncontaminated Atlantic Ocean; (2) oil extracted from herring caught in the contaminated Baltic Sea; or (3) the Atlantic herring oil extract spiked with 2,3,7,8-TCDD. The daily intakes of aryl hydrocarbon (Ah)-receptor dependent toxic equivalents (TEQ) for mothers were 0.3 in the Atlantic group, 2.1 in the Baltic group, and 134 ng/kg body wt. in the 2,3,7,8-TCDD positive control group. Immune function and host resistance to rat cytomegalovirus (RCMV) were assessed in ospring aged 11, 25, 46 or 59 days. Rat pups in the positive control TCDD-spiked group exhibited immunosuppression characterized by reduced thymus weight and cellularity, reduced thymocyte and splenocyte proliferative responses to T-dependent mitogens in vitro, reduced virus-associated natural killer (NK) cell and speci®c antibody responses. While less pronounced, a similar pattern of eects was observed in the rat pups exposed only to the Baltic Sea herring oil. These immunotoxic eects were transient in both exposure groups, with a time-related recovery in immune function possibly due to the half-life of TCDD in rats and the waning exposure levels in the rapidly growing pups. We previously demonstrated that the same Baltic Sea herring led to impaired natural killer cell and Tlymphocyte function in harbour seals during the course of a long-term captive feeding study. The collective results of these studies in rats and seals indicate the immunotoxic potential of environmental mixtures at current levels in the aquatic environment, and suggest that the developing immune system of young mammals may be at particular risk.

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Transfer and distribution of accumulated (14C)polychlorinated biphenyls from maternal to fetal and suckling rats

Cited by 50 publications

References 22 publications

Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein

Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Impaired cellular immune response in rats exposed perinatally to Baltic Sea herring oil or 2,3,7,8-TCDD

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