Effects of waterborne exposure to 4-nonylphenol on plasma sex steroid and vitellogenin concentrations in sexually mature male carp (Cyprinus carpio).

4-Nonylphenol (NP) has been shown to elicit estrogenic responses both in vivo and in vitro. The mechanism by which NP exerts estrogenic and other endocrine-modulating effects in vivo remains unclear, however. The goal of this study was to evaluate the ability of NP to elicit estrogenic responses through indirect mechanisms of action involving the modulation of endogenous steroid hormone concentrations. Sexually mature male common carp (Cyprinus carpio) were exposed to aqueous NP concentrations ranging from <0.05 to 5.4 microg NP/l for 28-31 d. Approximately 0.5-3.5 ppm of NP was detected in pooled plasma samples or tissue samples from the carp studied. NP exposure did not significantly increase plasma concentrations of 17beta-estradiol (E2), testosterone (T) or vitellogenin (VTG). Excluding outliers, plasma E2 concentrations ranged from <175 to 700 pg E2/ml. T concentrations ranged from 940 to 24,700 pg T/ml plasma. The greatest VTG concentration detected was 52 microg/ml. One-third of the plasma samples tested contained <1 microg VTG/ml. Overall, the results of this study did not support the hypothesis that exposure to waterborne NP can modulate concentrations of steroid hormones in the plasma of sexually mature male carp. The results did, however, raise a number of questions regarding the utility of estradiol equivalent (EEQ) estimates as a means of predicting in vivo effects of estrogenic substances. Furthermore, they provide information regarding the concentrations and variability of E2, T, and VTG in the plasma of sexually mature male carp, which may aid in design and interpretation of future studies.

Internalization of ionotropic glutamate receptors in response to mGluR activation.

Activation of group 1 metabotropic glutamate receptors (mGluRs) stimulates dendritic protein synthesis and long-term synaptic depression (LTD), but it remains unclear how these effects are related. Here we provide evidence that a consequence of mGluR activation in the hippocampus is the rapid loss of both AMPA and NMDA receptors from synapses. Like mGluR-LTD, the stable expression of this change requires protein synthesis. These data suggest that expression of mGluR-LTD is at least partly postsynaptic, and that a functional consequence of dendritic protein synthesis is the regulation of glutamate receptor trafficking.

Bioconcentration of nonylphenol in fathead minnows (Pimephales promelas).

Bioconcentration of p-nonylphenol (NP) by fathead minnows was determined under laboratory conditions. Fish were exposed continuously for 42 days to 0.33, 0.93 and 2.36 microg NP/l in a flow-through system. NP was Soxhlet extracted from whole fish homogenates with dichloromethane (DCM). The resulting extract was concentrated and bulk lipids removed by gel permeation and silica-gel chromatography. Compounds were identified and quantified by reverse-phase high-pressure liquid chromatography (RP-HPLC) with fluorescence detection. Mass spectrometry was used for verification of peak assignments. Bioconcentration factors (BCFs) ranged from 245 to 380.

Effects of nonylphenol ethoxylate exposure on reproductive output and bioindicators of environmental estrogen exposure in fathead minnows Pimephales promelas.

Nonylphenol ethoxylates (NPEOs) were evaluated in the laboratory for potential effects on the reproductive physiology and fecundity of fathead minnows (Pimephales promelas). Groups of three adult male and three female fathead minnows were exposed in a continuous flow-through system to 0, 0.21, 0.65, 2.1, or 7.9 microg NPEO/L for 42 d. Rabbit anti-goldfish vitellogenin (VTG) antiserum was prepared and a competitive enzyme-linked immunosorbent assay (ELISA) was adapted for measurement of plasma VTG in fish following exposure. Plasma 17beta-estradiol (E2) and testosterone (T) were also quantified by ELISA at the end of the exposure. Neither survival nor fecundity of fathead minnows exhibited a concentration-dependent response to NPEOs. No significant differences were observed in plasma VTG concentrations among treatments for males or females. Mean plasma VTG concentrations in females ranged from 291.7 to 895.1 microg VTG/ml among treatments and did not overlap with mean concentrations measured in the plasma of males, which ranged from less than the method detection limit (0.27 microg VTG/ml) to 3.2 microg VTG/ml. Plasma E2 concentrations exhibited a significant difference between males and females within all NPEO treatments, but no differences were observed among treatments. Similarly, plasma T concentrations did not exhibit a concentration-dependent response to NPEOs.

Identification and quantification of estrogen receptor agonists in wastewater effluents.

Total concentrations of several known xenobiotic estrogen receptor (ER) agonists and natural and synthetic estrogen were measured in water by use of a combination of instrumental and bioanalytical approaches. Samples from 3 municipal wastewater treatment plants (WWTPs) in south central Michigan (upstream and effluent); 4 point source locations on the Trenton Channel of the Detroit River, MI; and 5 locations in Lake Mead, NV were analyzed. Organic compounds were extracted from 5 L water samples using solid-phase extraction disks and separated into three fractions based on polarity. Whole extracts and fractions were tested for ER agonist potency using the MVLN in vitro bioassay. ER agonist potency was characterized by comparing the magnitude of induction elicited by the extract or fraction to the maximum induction caused by 17beta-estradiol (E2). The greatest concentrations of ER agonists were associated with the most polar fraction (F3). Instrumental analyses and further fractionation were used to identify specific ER agonists associated with bioassay responses. Bioassay data were compared to extract concentrations in order minimize variability associated with the extraction procedure. Concentrations of endogenous estrogen, E2, and the synthetic estrogen ethynylestradiol (EE2) ranged from nondetectable to 14.6 ng/mL extract (nondetectable to 3.66 ng/L water) and represented from 88 to 99.5% of the total estrogen equivalents in the water samples analyzed. Concentrations of alkylphenols (APs) ranged from nondetectable to 148 microg/mL extract (nondetectable to 37,000 ng/L water). In general, alkylphenols contributed less than 0.5% of the total estrogen equivalents in the water samples. Both bioassay-directed fractionation results and comparison of ER agonist concentrations, adjusted for their known relative potencies, support the conclusion that E2 and EE2 were the dominant environmental estrogens in water samples from mid-Michigan and Lake Mead, NV.

Occupational exposures during the World Trade Center disaster response.

Upon the request of the New York City Department of Health, the Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health (NIOSH) monitored occupational exposures among emergency response workers during the rescue and recovery activities at the World Trade Center disaster site from September 18 through 4 October 2001. During this period, over 1,200 bulk and air samples were collected to estimate or characterize workers' occupational exposures. Samples were collected and analyzed for asbestos, carbon monoxide (CO), chlorodifluoromethane (Freon 22), diesel exhaust, hydrogen sulfide, inorganic acids, mercury and other metals, polynuclear aromatic hydrocarbons, respirable particulate not otherwise regulated (PNOR), respirable crystalline silica, total PNOR, and volatile organic compounds. Exposures to most of these potential hazards did not exceed NIOSH Recommended Exposure Limits or Occupational Safety and Health Administration Permissible Exposure Limits. However, one torch cutter was overexposed to cadmium and another worker (and possibly three others) was overexposed to CO. The elevated cadmium and CO levels were the result of workers using oxy-acetylene cutting torches and gasoline-powered cutting saws. Recommendations were made to ensure adequate ventilation and worker understanding when using these tools and, where possible, to substitute rechargeable, battery-powered cutting saws for gasoline-powered ones. Toxicology

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part IV: Results from representative chemicals, sensitivity analysis, and discriminatory power.

The Chemical Scoring and Ranking Assessment Model (SCRAM) has been described in Parts I-III of this series (Snyder et al.: , 1999a; 1999b; 1999c). SCRAM is a chemical scoring and ranking (CSR) system that scores chemicals on the basis of bioaccumulation potential, environmental persistence, and toxicity. Part IV describes various tests and descriptions of the performance of this system. A group of 21 representative chemicals was chosen and scored to test the system. For those chemicals, the percentages of the scores associated with fate-related properties and associated with data uncertainty were determined. The scoring of four of these chemicals is described in greater detail, and the suitability of the scores is discussed. An analysis of the sensitivity of the system to incomplete data sets is presented. And finally, the discriminatory power of the system is described.

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part II: Bioaccumulation potential and persistence.

Part I (Snyder et al.: , 1999a) of this series introduced SCRAM, a chemical scoring and ranking system for contaminants of the North American Great Lakes. Here, in Part II, scoring of the bioaccumulation potential and persistence of chemicals is discussed, including acceptable types of data, specific scoring instructions, and the basis for criteria and scores for these categories of the system. Difficulties encountered during the process of determining which types of data adequately represent the properties of interest are discussed. Also, justification is given for an emphasis on scoring on the basis of persistence.

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part III: Acute and subchronic or chronic toxicity.

In Part I of this series (Snyder: et al., 1999a), the Chemical Scoring and Ranking Assessment Model (SCRAM) was introduced. This system produces scores for chemicals based on their bioaccumulation potential, environmental persistence, and toxicity. In Part II, scoring of the potential for a chemical to persist in the environment and bioaccumulate was described (Snyder et al., 1999b). In Part III, scoring of chemical toxicity is discussed, including definitions and descriptions of effects that are scored, specific scoring instructions, the basis for the criteria and scores, and specific conditions or concerns regarding the types of data used for scoring. A score for each chemical screened is determined from available test data from acute or subchronic and chronic toxicity tests conducted on aquatic and terrestrial organisms. Subchronic and chronic human health effects, including carcinogenicity, are also considered. Part IV includes an evaluation of the performance of the scoring and ranking system (Snyder: et al., 1999c).

SCRAM: A scoring and ranking system for persistent, bioaccumulative, and toxic substances for the North American Great Lakes. Part I: Structure of the scoring and ranking system.

Hundreds of chemical contaminants have been identified in the Great Lakes System of North America. Depending on the agency or organization, various subset lists of these contaminants have been identified as chemicals of potential concern. However, there is no agreement on the method that should be used to make management decisions. Except for consensus on approximately 40 chemicals that most North American agencies agree can cause deleterious effects if released into the environment, no agreement has been reached regarding the priority that contaminants should receive for further action. That leaves hundreds of chemicals that have been, are being, or potentially could be released into the environment that have not been evaluated yet. A profile for potential chemicals of concern is generally thought to include persistence in the environment, potential to bioaccumulate, and ability to cause toxic effects at environmentally relevant concentrations. Except for the International Joint Commission's definition of persistence (> 8 weeks residence time in air, water, soil or sediment), there is little concurrence about what defines these characteristics. For instance, the State of Michigan currently has no established definitions or profiles of persistent, bioaccumulative, toxic substances. Furthermore, there is no standard process to rank chemicals relative to these characteristics. The Chemical Scoring and Ranking Assessment Model (SCRAM) has been developed to provide a process to rank-order chemicals based on these characteristics. The SCRAM system was developed primarily for use in the Great Lakes region of North America and particularly in Michigan, but it is not site-specific. Use of this system may assist in pollution prevention activities and other future chemical control efforts, allowing attention to be focused first on those chemicals likely to present the greatest hazard.

Effects of waterborne exposure to 4-nonylphenol and nonylphenol ethoxylate on secondary sex characteristics and gonads of fathead minnows (Pimephales promelas).

Fathead minnows were exposed to 4-nonylphenol (NP) or nonylphenol ethoxylate (NPEO) to determine the effects of these weak estrogen agonists on secondary sex characteristics and gonads of sexually mature males and females during 42-day continuous-flow exposures. Neither NP nor NPEO caused statistically significant effects on tubercles or fatpad size at the concentrations tested. Exposure to 1. 1 or 3.4 micrograms NP/L caused changes in the number and size of Sertoli cells and germ cell syncytia. Necrotic aggregates of various stages of germ cells in the spermatogenic sequence were observed in the testes of males exposed to NP. Electron microscopy of the testes of NP-exposed males revealed the presence of phagocytic cells in the lumina of seminiferous tubules. The cytoplasm of some Sertoli cells was distended with myelin figures and necrotic spermatozoa. No significant effects on the stages of follicular development were observed in females exposed to NP. There were no differences in the gonads or secondary sex characteristics of males or females exposed to 5.5 micrograms NPEO/L, the greatest concentration studied. The histologic responses observed are sensitive indicators of waterborne exposure to NP at environmentally relevant concentrations, but not as sensitive as induction of plasma vitellogenin. The secondary sex characteristics were not affected by concentrations of NP or NPEO as great as 3.4 or 5.5 micrograms/L, respectively. Histologic responses occurred at concentrations that were less than the final chronic value based on survival and approximately the same as those required to cause effects on egg production. The histologic effects caused by NP were similar to, but not exactly the same as those caused by exposure of fathead minnows to 17 beta-estradiol.

Evaluation of platelets collected by a new portable apheresis device.

We studied the efficiency of platelet collection by the Mobile Collection System (MCS) using two types of experimental protocols and evaluated the effect of storage at 22 degrees C on the platelet concentrates (PC). MCS is a new blood cell separator that combines discontinuous flow features with a new computerized operating system and can be used to harvest either full units of apheresis PC (SDP protocol) or half units of PC together with one to two units of plasma (PLP protocol). On the average, 1.98 x 10(11) +/- 0.46 x 10(11) (mean +/- SD) platelets were obtained by the PLP protocol and 3.01 x 10(11) +/- 0.70 x 10(11) and 4.2 x 10(11) +/- 1.12 x 10(11) by the early and later versions of the SDP protocols, respectively. The mean number of WBC per PC ranged from 3.3 to 4.7 x 10(8). During the storage period pH stayed above 7.0. On the average, the production of one molecule of lactate corresponded to the consumption of 0.538 molecules of glucose, indicating that less than 8% of glucose was consumed by the oxidative pathway. There were only small increases in LDH and B thromboglobulin concentrations. Furthermore, the ability of platelets to recover from osmotic shock and to aggregate following exposure to dual agonists declined only slightly during storage, indicating that both viability and function of platelets collected by the MCS were preserved during storage.

The 3 and 2 technique for Hodgkin's disease at Memorial Hospital.

This paper presents a technique for total nodal irradiation used at Memorial Hospital for the treatment of Stage IIIA and previously untreated Stage IIIB Hodgkin's disease. This method of treating large fields for this type of lymphoma overcomes problems of dosimetry and treatment tolerance. There are two courses of treatment used in which all lymph node bearing areas from the tips of the mastoids to the femoral triangles are irradiated. A comparison will be made between this technique and the conventional treatment fields for Hodgkin's disease.

Virulence and pathogenesis of yellow fever virus serially passaged in cell culture.

Viscerotropic virulence of the Asibi strain of yellow fever virus (YFV) for monkeys has been known to be lost after serial passage in HeLa cell monolayers. This phenomenon was investigated in several other mammalian and insect tissue cell lines. Assay in monkeys of original seed virus and of virus after 7 and 11 passages in a porcine kidney cell line (PK) indicated essentially equal infectivity and mortality. Moreover, monkeys receiving the passaged virus exhibited more rapid onset of disease and death than animals infected with original seed virus. Histological changes in animals inoculated with passaged virus were identical to those in animals receiving the seed virus. Virus from later passages in PK cells was also lethal for approximately 50% of the monkeys; however, evidence for progressive attenuation was seen in these preparations. Similar results were obtained with a mosquito (Aedes aegypti) cell line. In contrast to results obtained in PK and mosquito cells, YFV became essentially avirulent (nonlethal and less infective) for monkeys after only seven passages in HeLa cell cultures.

Experimental irradiated arthrospore vaccine against coccidioidomycosis in mice.

An experimental irradiated ((60)Co) arthrospore vaccine against coccidioidomycosis protected approximately 75% of mice from death after an intraperitoneal challenge sufficient to kill approximately 90% of the nonimmunized control mice. Although the majority of the immunized mice became infected with Coccidioides immitis, the histologic lesions were substantially less severe than those in the nonimmunized controls, particularly in the pulmonary region. Although arthrospores irradiated with 1, 2, or 3 million roentgens lost their ability to multiply in various laboratory media (probably through interference with cell division), partial conversion to the parasitic phase (spherule) was observed after animal inoculation (rounding out of arthrospores into immature spherules, but without development of endospores). Duration of viability of these structures has yet to be determined.