ISSN:0260-437X    

DOI:10.1002/jat.2550050402

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe acute toxicity of chemicals to rainbow trout, as shown by intraperitoneal injections (IP LD50), oral dosing (oral LD50) and aqueous exposure (LC50) was compared with published values for IP LD50s and oral LD50s of mice and rats. The method of comparison was by simple linear regression analyses of log‐transformed data, modified to recognize thatX(fish toxicity) was neither fixed nor measured without error.Within‐species comparisons demonstrated very strong linear correlations (r=0.866–0.998) between IP and oral LD50s. Variability was least for the fish data since it was all generated in one laboratory.Comparisons between species of IP and oral LD50S gave correlation coefficients ranging from 0.59 to 0.95 with the majority over 0.80. Correlations were best (r=0.83–0.94) between fish LD50s and rat and mice IP LD50s. Correlations were poorest between fish and mammalian oral LD50s (r=0.59–0.66) because the sample sizes and the ranges of values were very small. In all cases, the slopes were close to, or equalled, 1.0.Comparisons of fish LC50s to fish or mammalian LD50s were not as successful. Correlation coefficients ranged from 0.19 to 0.83. Presumably the cause was the aqueous exposure. Interactions of the chemicals with water (e.g. dissociation) and with lipid membranes (partitioning) should cause considerable variations in uptake efficiency. However, adjustments of LC50s for dissociation constants and partition coefficients did not improve these correlations, probably because there were few chemicals for which all data were available.These comparisons demonstrate a potential for a wider use of surrogate species in toxicity testing and for adapting existing data from mammalian toxicology to aquatic hazard as

ISSN:0260-437X    

DOI:10.1002/jat.2550050403

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThis report concerns an evaluation of threein vitroteratogenesis tests: theDugesiaregeneration assay, theHydrareaggregation assay and theXenopusembryo assay. Our approach involves the establishment and/or refinement of test protocols, definition of endpoints, and evaluation of test performance by comparison with available results ofin vivomammalian studies. Chemicals used for preliminary evaluation studies were the known mammalian teratogens, vinblastine sulfate (VIN) and hydroxyurea (HU), a coeffective teratogen, cadmium chloride (Cd), and an National Toxicology Program priority chemical, 9‐aminoacridine hydrochloride (9AA). TheDugesiaassay takes advantage of the ability of beheaded flatworms to regenerate and can be completed in 7–14 days. Concentrations of VIN of 3.2 mg 1−1inhibited auricle formation and further regeneration observed in 3–6 days. Similarly, eyespot and auricle formation was blocked by HU (180 mg 1−1). The duration of regeneration, measured as the time elapsed between decapitation and eyespot formation (control =5 days), was extended by 1–4 days during exposure to 9AA. Sublethal Cd had little effect on regeneration. TheHydraassay is an evaluation of the ability of dissociated cells to regenerate complete organisms when randomly reassociated. A teratogenic test substance is detected by observing the ratio of the minimal effective concentrations of a substance between intact organisms and regenerates. Compounds with a ratio>2.0 are potential teratogens. The ratios determined for 9AA, VIN, HU and Cd, respectively, were 10.0, 4.0, 2.7 and 1.2. These results indicate that the first three compounds tested positive for teratogenesis. TheXenopusassay has several endpoints, all of which can be compared with embryolethality in order to index teratogenic hazard. A 4‐day test encompasses development from the blastula stage, through hatching, to formation of swimming tadpoles. Reduced growth was noted during exposure to HU concentrations above 50 mg 1−1(embryolethality of HU was above 200 mg1−1). Significant skeletal abnormalities, recorded as moderate to severe spinal curvature and resultant loss of swimming ability, were observed during exposure to all four test chemicals. However, this phenomenon was apparent at non‐embryolethal concentrations only for HU and VIN. Further abnormalities, such as altered skin pigmentation and osmoregulatory failure

ISSN:0260-437X    

DOI:10.1002/jat.2550050404

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe FETAX (Frog Embryo Teratogenesis Assay —Xenopus) whole embryo bioassay has been developed to screen for environmental substances that cause birth defects. We have used this assay to test its effectiveness in working with actual water samples from the field. Tar Creek is contaminated by discharges from abandoned lead and zinc mines. In addition to high concentrations of zinc, iron and other metals, water samples are routinely low in pH and oxygen content. The pH values of three Tar Creek sample sites were below the established tolerance limits of the embryos. Therefore, one group of samples had no pH adjustment while a second group had the pH adjusted to 7.0. Two of the four sites contained agents that reduced embryonic growth and caused high rates of mortality. A third site contained teratogenic substances. We have determined that metal content is responsible, along with the low pH, for the biologic effects. We have identified high concentrations of toxic metals in Tar Creek by water analysis and were able to demonstrate, by removing metals via Chelex® 100 ion exchange chromatography, that the observed toxicity and teratogenicity were caused by metal ions.We have concluded that FETAX is an excellent test for complex mixtures. Physicochemical parameters, such as pH, oxygen and metals content, can be altered and the effect of these changes on toxicity and teratogenicity determined using FETAX. The interaction of toxic substances and low pH are important when considering embryo survival and developme

ISSN:0260-437X    

DOI:10.1002/jat.2550050405

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractA method for evaluating pollutant genotoxicity, embryotoxicity and teratogenicity using sea urchin embryos has been developed and was tested using benzo (α) pyrene (BP). Initial results suggested that the bioassay may be a sensitive indicator of pollutant toxicity and mutagenicity since several endpoints can be simultaneously assessed. The bioassay is rapid, inexpensive and appears applicable to a variety of toxicants and delivery methods. The test is based upon the standard 48 h sea urchin development assay and incorporates cytologic–cytogenetic analysis of embryos. Following toxic exposure of gametes, fertilization success is assessed. Embryos then develop for 48 h at which time survival and teratogenesis are evaluated. A subsample of embryos is stained and dissociated into monolayers and mitotic configurations are examined using light microscopy. Embryo mitotic rates are used as an indicator of overall embryonic health. Cytotoxic effects are concomitantly evaluated. Genotoxicity is measured using two methods: (1) anaphase aberration analysis, a technique which assesses abnormalities in the chromosome configurations (such as bridges and fragments) as the groups of chromosomes move to opposite poles and (2) micronucleus formation, a procedure examining the incidence of smaller, secondary nuclei composed of whole chromosomes or chromatid fragments. These two measurements preclude the need to examine individual chromosomes for deletions and exchanges, a laborious process in most aquatic organisms which possess numerous relatively small chromosomes.This genotoxicity–teratogenicity test appears promising for laboratory evaluations of individual substances or of complex chemical mixtures as weii as for environmental monitoring of nearshore areas. The standard development assay has been used to screen pharmaceuticals and environmental contaminants and some recent investigations have included mitotic aberration analysis. Experiments in our laboratory suggest that the genotoxicity–teratogenicity test may be a feasible approach to field monitoring. Mutagen loads of spawning adult urchins could be assessed by conducting cytologic–cytogenetic analysis of resulting embryos although initial studies suggest that this method is less sensitive than direct embryo e

ISSN:0260-437X    

DOI:10.1002/jat.2550050406

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractAn intermittent‐flow exposure system was designed to provide stable and manipulative concentrations of volatile and hydrophobic compounds to small aquatic animals for uninterrupted long periods. Test species for 28‐day experiments included two aquarium fishes, the Japanese medaka (Oryzias latipes) and the king cobra guppy (Poecilia reticulata). Test chemicals included trichloroethylene, vinylidene chloride, bis (2‐chloroethyl)ether, ethylene dichloride, and a mixture of carbon tetrachloride, trichloroethylene, chloroform, bromodichloromethane, chlorodibromomethane and bromoform. These compounds are drinking water biorefractories and are potentially carcinogenic. Concentrated aqueous toxicant solutions, delivered from a remote triple carboy dispensing system, were mixed with diluent water within an isolated chamber containing exposure aquaria and test fish. Toxicant concentrations measured throughout each exposure period proved to be stable within acceptable variability ranges as indicated by coefficients of variation generally less tha

ISSN:0260-437X    

DOI:10.1002/jat.2550050407

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractFor small fish species to be utilized as models for carcinogenicity testing they should be capable of developing neoplasms, preferably in multiple tissues, when exposed to known carcinogens. Seven species of small fish were exposed to methylazoxymethanol acetate (MAM‐Ac) and tumor development was monitored. Specimens 6–10 days old were exposed to nominal concentrations of MAM‐Ac up to 100 mg l−1for 2 h, then transferred to carcinogen‐free water. Hepatic neoplasms developed in the Japanese medaka, guppy, sheepshead minnow, Gulf killifish, inland silverside, rivulus, and fathead minnow. Additionally, neoplasms occurred in other organs and tissues of the medaka (retina, various mesenchymal tissues, exocrine pancreas, kidney, and nervous tissue), guppy (mesenchymal tissue, exocrine pancreas, and kidney), and sheepshead minnow (choroid gland, mesenchymal tissues, and nervous tissue). All tumors were diagnosed in specimens within 1 year post‐exposure. Early signs of liver tumors appeared in medaka and guppy at about 1 month post‐exposure. These studies show that both medaka and guppy would be good models because they appear sensitive to carcinogens, develop tumors in multiple tissues and are easy to breed and maintain. Certain other small fish species also may prove to be good models because of habitat preferences, breeding strategies, or genet

ISSN:0260-437X    

DOI:10.1002/jat.2550050408

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractWithin the last decade unusually high frequencies of neoplasms have been reported in feral fish populations from a variety of locations. At many of these locations organic carcinogens have been noted as a potential cause. We sought to identify toxic effects including neoplasia in fish exposed to an organic carcinogen, and to quantify these effects through time.We exposed guppies (Poecilia reticulata) to multiple doses of DEN, an organic carcinogen. Fish were then subsampled and examined for liver histopathology at 2‐month intervals over 12 months. Necrotic zones, macrophage centers, bile duct proliferations, enlarged lipid deposits, neoplastic foci, cholangiocarcinomas and hepatoblastomas were quantified by frequency of occurrence and the percentage of liver area involved.DEN toxicity resulted in necrotic zones that peaked in frequency at the first sample period (2 months). Lipid deposits increased, then plateaued in guppies, indicating a more chronic toxic effect. Similarly, macrophage centers increased through the sampling period. Bile duct proliferation appeared to be of two types: a reversible toxic response which peaked at 4 months and then declined and a less frequent irreversible proliferation which continued to develop into cholangiocarcinoma. Neoplastic foci of mixed hepatocytes and cholangiocytes increased in livers of exposed guppies from the second month, developing into hepatoblastomas, which occurred in almost 100% of exposed guppies by the twelfth month. The irreversible bile duct proliferations and the neoplastic foci had cellular densities different from corresponding control tissue and similar to cellular densities of cholangiocarcinomas and hepatoblastomas, respectivel

ISSN:0260-437X    

DOI:10.1002/jat.2550050409

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550050401

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY