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Pesticide induced ouabain resistant mutants in Chinese hamster V79 cells.

The effect of 3 insecticides (chlordane, dieldrin and carbaryl) and one herbicide (2,4-D-fluid) was studied on the induction of ouabain-resistant mutants in Chinese hamster V79 cells at concentrations approaching the Environmental Protection Agency (EPA) tolerance limits. The kinetics and dose range for cytotoxicity were determined by colony formation assay. Results showed that these compounds enhanced the number of ouabain-resistant mutants and acted as weak mutagens.

2,4-Dichlorophenoxyacetic Acid↗

Analysis of oxyhalide disinfection by-products and other anions of interest in drinking water by ion chromatography.

The US Environmental Protection Agency is developing regulations for various drinking water disinfection by-products (DBPs). This effort involves developing analytical methods for the DBPs formed as a result of different disinfection treatments and collecting occurrence data for these species. Ion chromatography is one method being used to analyze drinking water samples for the following inorganic DBPs: chlorite, chlorate and bromate. These anions, however, are difficult to separate from common interfering anions of chloride, carbonate and nitrate. A method is therefore presented by which tetraborate/boric acid is used to separate these anions. Method detection limits of the order of 10 micrograms/l, using conductivity and UV detection were obtained. Stability studies of chlorite showing the effectiveness of ethylenediamine as a preservative and summary data for an occurrence of nitrite, nitrate and the DBP precursor bromide are presented.

Anions↗

Detection of substituted benzenes in water at the pg/ml level using solid-phase microextraction and gas chromatography-ion trap mass spectrometry.

Solid-phase microextraction (SPME) is combined with gas chromatography-ion trap mass spectrometry (GC-IT-MS) for the analysis of benzene, toluene, ethyl benzene and xylene isomers (BTEX) in water. SPME is a recent technique for extracting organics from an aqueous matrix into a stationary phase immobilized on a fused-silica fiber. The analytes are thermally desorbed directly in the injector of a gas chromatograph. The wide linear dynamic range (five orders of magnitude) and pg sensitivity of the ion trap mass spectrometer in its full scan mode is an ideal detector for identifying and quantifying the analytes extracted with an SPME device. The combined method SPME-GC-IT-MS, using fibers coated with a 100-microns polydimethylsiloxane coating, showed a limit of quantitation (LOQ) of 50 pg/ml benzene in water. This corresponds to 5 pg of benzene absorbed onto the fiber. The limit of detection (LOD) was 15 pg/ml benzene. For o-xylene spiked at 50 pg/ml in water 50 pg were absorbed by the fiber indicating an LOQ and LOD 10 times better than for benzene. The detection limits obtained exceed the requirements of both the United States Environmental Protection Agency method 524.2 and the Ontario Municipal/Industrial Strategy for Abatement program, which range from 30 to 80 pg/ml and 500 to 1100 pg/ml, respectively. The linearity of the method extended over five orders of magnitude. Relative standard deviation ranged from 2.7 to 5.2% for 15 ng/ml BTEX in water and from 5.5 to 7.5% for 50 pg/ml BTEX in water. SPME-GC-IT-MS was used to evaluate the contamination level in laboratory, potable and wastewater sources.

Benzene Derivatives↗

Determination of phenols at the ng/1 level in drinking and river waters by liquid chromatography with UV and electrochemical detection.

Solid-liquid extraction of samples and liquid chromatography with UV and electrochemical detection with laboratory-made microcolumns were applied to the separation and identification of phenols and substituted phenols in waters. The compounds mainly studied were the eleven phenols considered as priority pollutants by the US Environmental Protection Agency. Chromatographic separation was carried out with several water-methanol isocratic mobile phases; use of the autoincrement mode of the electrochemical detector allowed the compounds in the samples to be confirmed. The chromatographic system worked automatically. The detection limits obtained with prior concentration of the samples were 40-600 ng/l, depending of the phenol. Electrochemical detection was used for the determination of phenols in river and drinking waters; phenols at the ng/l level was detected.

Chromatography, Liquid↗

The present lack of evidence for unique rodent germ-cell mutagens.

Six chemicals, diethylhexyl phthalate (DEHP), ethanol, cyclohexylamine (CHA), sodium saccharin (NaS), cadmium chloride (CdCl2) and triflupromazine (TFP), were suggested to be unique germ-cell mutagens (Auletta and Ashby, 1988) by the GeneTox Workgroups of the U.S. Environmental Protection Agency (EPA). If this is a correct classification it would have major consequences when screening for mutagenicity and when labelling genotoxic substances. However, our re-evaluation of the GeneTox literature, including some more recent publications, has failed to find substantive evidence that any of these chemicals have been unequivocally established as having unique mutagenic activity in germ cells. For DEHP, NaS and TFP the evidence for genotoxic/mutagenic effects is questionable, in both germinal and somatic cells. Ethanol and CdCl2 showed clastogenic activity, but it was not restricted to germ cells. Both, ethanol and cadmium salts, appear to induce aneuploidy. The unconfirmed clastogenic effect of CHA was restricted to rats, but it occurred in both bone marrow and spermatogonia. Therefore, the general observation that rodent germ-cell mutagens are also genotoxic in somatic cells in vivo (Brusick, 1980; Holden, 1982) remains valid.

Animals↗

Dioxins in U.S. food and estimated daily intake.

Congener-specific analyses for polychlorinated dioxins and dibenzofurans were performed on eighteen dairy, meat, and fish samples obtained from a supermarket in upstate New York. Dioxin toxic equivalents (TEqs) on a whole or wet weight basis for these food samples ranged from 0.02 to 1.5 parts per trillion (ppt). Data on American food consumption rates were used to estimate a U.S. range of dioxin intake from food. Based on these first congener-specific dioxin analyses of U.S. food, U.S. average daily intake of "International" dioxin toxic equivalents for an adult weighing 65 kilograms (kg) was estimated to be between 18 to 192 picograms TEq or 0.3 to 3.0 picograms per kilogram of body weight. Our previous results for cow's milk, human breast milk, and soy-based infant formula were used to calculate intake for infants. The relatively high level of dioxins commonly reported in human breast milk from America contributes from 35 to 53 picograms of dioxin toxic equivalents per kilogram of body weight to the nursing infant per day in its first year of life. This value greatly exceeds the U.S. Environmental Protection Agency estimated dose which would lead to one excess cancer per one million people of 0.006 pg of TCDD per kg of body weight per day over a seventy year lifetime or similar reference doses used by some other countries of up to 10/pg/kg/day over a 70 year lifetime.

Adult↗

Significance and behaviour of heavy metals in wastewater treatment processes. IV. Water quality standards and criteria.

Literature on the health aspects of the presence of heavy metals in water and wastewaters is reviewed and quality standards, criteria and legislation promulgated by the World Health Organisation, European Economic Community, U.S. Environmental Protection Agency and Government of the U.S.S.R. are assessed and compared. It is evident from the literature that standards applied differ according to the projected water use and that although standards for potable water are generally based on human health criteria, other factors including available technology and economics may be limiting. Emphasis has been placed on the protection of raw water quality as a result of the limited ability of potable water treatment processes to remove certain heavy metals. It is apparent that limitations on heavy metals in discharges from the chlor-alkali and cadmium salts and pigments industries are more stringent in the United States than in the European Economic Community. It is concluded that the finite availability of unpolluted freshwater will result in greater water re-use and that appropriate standards are required to protect potable supply, raw water and agricultural land from contamination by heavy metals.

Europe↗

Chernobyl--its impact on Austria.

The nuclear reactor accident of 26 April 1986 in Chernobyl, USSR, led to numerous investigations in Austria concerning radiation levels in the environment. Consequently measures were drawn up by the Austrian government in an effort to minimize the doses to the general public. The paper gives a general view of the programs set up by the Austrian Environmental Protection Agency and others in trying to assess basic measurement parameters.

Accidents↗

Heavy metal accumulation and transport through detention ponds receiving highway runoff.

Sediment accumulations and associated heavy metal concentrations into retention/detention ponds receiving highway runoff from several ponds and metal concentrations in various sediment layers were analyzed to determine the extent of vertical migration. Extraction of heavy metals had been evaluated using various solutions including the United States Environmental Protection Agency Toxicity Characteristics Leaching Procedures (TCLP). Also, sediments were incubated under various conditions of redox potential and pH to investigate the effects of changes in sediment conditions on the stability of metal-sediment associations.

Florida↗

Examination and chemical treatment of industrial solid wastes for safe land application. I. Evaluation of toxic elements present in solid wastes from a fertilizer and chemical plant.

Four solid wastes from a fertilizer/chemical plant located in the area of Thessaloniki are examined using the U.S. Environmental Protection Agency's (EPA) extraction procedure for toxicity in order to determine their content of toxic elements. Analyses of the extracts indicate that one of the samples generates arsenic at a concentration which exceeds the EPA criterion level for this element by nearly 50 times. Another sample is characterised by pH values that are below the EPA minimum values; however, the toxic element concentration does not exceed EPA limits. The extractability of toxic elements from the solid wastes using various extracting solutions is also examined in order to determine the chemical conditions under which the toxic compounds are soluble.

Greece↗

Toxicity of selected priority pollutants to various aquatic organisms.

Toxicity tests were conducted with selected compounds listed by the United States Environmental Protection Agency (EPA) as priority pollutants. Acute toxicity information was determined for acenaphthene, arsenic trioxide, cadmium chloride, mercury(II) chloride, silver nitrate, chlordane, endosulfan, and heptachlor. Acute tests were conducted using one or more of the following species: fathead minnows (Pimephales promelas), channel catfish (Ictalurus punctatus), rainbow trout (Salmo gairdneri), brown trout (Salmo trutta), brook trout (Salvelinus fontinalis), bluegills (Lepomis macrochirus), snails (Aplexa hypnorum), or chironomids (Tanytarsus dissimilis). Acute values from these tests ranged from a silver nitrate 96-hr LC50 of 6.7 micrograms/liter for fathead minnows to an arsenic trioxide 48-hr LC50 of 97,000 micrograms/liter for chironomids. In addition to acute tests, a fathead minnow embryo-larval exposure was conducted with silver nitrate to estimate chronic toxicity. The estimated maximum acceptable toxicant concentration for silver nitrate, based on fathead minnow survival, lies between 0.37 and 0.65 micrograms/liter.

Animals↗

Mutagenicity, carcinogenicity and reproductive effects of dibromochloropropane (DBCP).

Dibromochloropropane (DBCP), a brominated organochlorine nematocide, has been used since the mid-1950s. Its primary value was its effectiveness on perennial crops without damaging the plants. DBCP also had less acute toxicity than earlier soil fumigants such as ethylene dibromide. DBCP became widely used on citrus, grapes, peaches, pineapple, soybeans and tomatoes. In Central America and Israel, banana trees were treated with DBCP. By 1975, 25 million pounds were being produced in the U.S. per year. The majority of U.S. production was applied in the Pacific Coast states, particularly California's San Joaquin Valley, and the Southern Atlantic Coast states. Animal studies in the early 1960s revealed hepatic and renal effects and testicular atrophy in DBCP-treated rates. Testicular atrophy was noted at the lowest exposure level tested (5 ppm). In 1973, DBCP was found to cause gastric carcinoma in mice and rats, and mammary adenocarcinoma in rats. A later study linked DBCP to nasal cavity tumors in rats. DBCP is an in vitro mutagen after activation with microsomal enzymes. A dominant lethal effect has been observed in rats. DBCP also induces increases in sister-chromatid exchanges and chromosomal aberrations. Mean fetal weight and maternal weight gain is decreased in pregnant rats exposed to DBCP. In mid-1977, employees in a California pesticide formulation plant were discovered to be infertile. Further investigations documented azoospermia and oligospermia among many of the workers handling DBCP. These findings were duplicated in other DBCP production plants. In the United States, the Occupational Safety and Health Administration (OSHA) and the Environmental Protection Agency (EPA) rapidly restricted the use of DBCP. The application of DBCP to all but pineapples in Hawaii was banned by the EPA in 1979. In 1982, the EPA exempted the peach crop in the Southern Atlantic coast states from the ban on DBCP use. Prior to the 1977 events, no such agent in workplace concentrations had been shown to produce infertility and sterility in otherwise healthy men. Subsequently, the interest in DBCP had led to many other studies, and has contributed to a heightened awareness about workplace hazards to both the male and female reproductive systems. This article will review the current state of knowledge of the in vitro, animal, and human toxicology of DBCP.

Animals↗

Application of the carcinogenicity prediction and battery selection (CPBS) method to the Gene-Tox data base.

The carcinogenicity prediction and battery selection (CPBS) method (Chankong et al., 1985) utilizes the results of short-term tests to predict the carcinogenicity of chemicals and select batteries of tests that are capable of giving accurate predictions at reasonable costs. The CPBS method has been applied to the data compiled under the aegis of the Gene-Tox Program of the U.S. Environmental Protection Agency as a demonstration of the method on a typical data base. A number of batteries were selected by the methodology as having superior performance characteristics. The Bayesian predictions resulting from most of the selected 3-assay batteries were very good (greater than 90% of the carcinogens were correctly identified). It was also found that the 3-assay batteries of specified composition gave generally more accurate predictions than batteries of 4 or more assays of unspecified composition. A number of problems which may have affected our results have been identified: (1) the reliability of the sensitivities and specificities of the individual assays, (2) the prior probability that a chemical is a carcinogen was assumed to be 0.5, and (3) we have not (as yet) taken into account that some of the carcinogens are non-genotoxic and will produce false negative assays results. We are currently investigating approaches to take these factors into consideration. Our analysis also indicates that more testing of chemicals for carcinogenicity (especially probable non-carcinogens) is needed to further enhance the predictive capability of the CPBS method.

Carcinogens↗

DNA adduct formation by 12 chemicals with populations potentially suitable for molecular epidemiological studies.

DNA adduct formation, route of absorption, metabolism and chemistry of 12 hazardous chemicals are reviewed. Methods for adduct detection are also reviewed and approaches to sensitivity and specificity are identified. The selection of these 12 chemicals from the Environmental Protection Agency list of genotoxic chemicals was based on the availability of information and on the availability of populations potentially suitable for molecular epidemiological study. The 12 chemicals include ethylene oxide, styrene, vinyl chloride, epichlorohydrin, propylene oxide, 4,4'-methylenebis-2-chloroaniline, benzidine, benzidine dyes (Direct Blue 6, Direct Black 38 and Direct Brown 95), acrylonitrile and benzyl chloride. While some of these chemicals (styrene and benzyl chloride, possibly Direct Blue 6) give rise to unique DNA adducts, others do not. Potentially confounding factors include mixed exposures in the work place, as well the formation of common DNA adducts. Additional research needs are identified.

Animals↗

The ability of plant genotoxicity assays to predict carcinogenicity.

A number of assays have been developed which use higher plants for measuring mutagenic or cytogenetic effects of chemicals, as an indication of carcinogenicity. Plant assays require less extensive equipment, materials and personnel than most other genotoxicity tests, which is a potential advantage, particularly in less developed parts of the world. We have analyzed data on 9 plant genotoxicity assays evaluated by the Gene-Tox program of the U.S. Environmental Protection Agency, using methodologies we have recently developed to assess the capability of assays to predict carcinogenicity and carcinogenic potency. All 9 of the plant assays appear to have high sensitivity (few false negatives). Specificity (rate of true negatives) was more difficult to evaluate because of limited testing on non-carcinogens; however, available data indicate that only the Arabidopsis mutagenicity (ArM) test appears to have high specificity. Based upon their high sensitivity, plant genotoxicity tests are most appropriate for a risk-averse testing program, because although many false positives will be generated, the relatively few negative results will be quite reliable.

Carcinogens↗

Reevaluation of the 9 compounds reported conclusive positive in yeast Saccharomyces cerevisiae aneuploidy test systems by the Gene-Tox Program using strain D61.M of Saccharomyces cerevisiae.

The state of aneuploidy test methodology was appraised by the U.S. Environmental Protection Agency in 1986 in analyzing published data. In Saccharomyces cerevisiae 9 chemicals were reported to be conclusive positive for aneuploidy induction in either mitotic or meiotic cells. We reevaluated these 9 chemicals using Saccharomyces cerevisiae D61.M, a strain that detects mitotic chromosome malsegregation. Acetone (lowest effective dose (LED): 40 microliters/ml), bavistan (LED: 5 micrograms/ml), benomyl (LED: 30 micrograms/ml) and oncodazole (LED: 4 micrograms/ml) induced a dose-dependent increase in the frequencies of chromosomal malsegregation. Ethyl methanesulfonate (EMS; highest tested dose (HTD): 1000 micrograms/ml) and methyl methanesulfonate (MMS; HTD: 100 micrograms/ml) did not induce malsegregation but were both potent inducers of other genetic events, detected by an increase in the frequencies of cyhR cells. No increases in both endpoints (malsegregation and other genetic events) were observed after treatment of S. cerevisiae D61.M with cyclophosphamide (CP; HTD: 16 mg/ml) in the absence of S9, p-D,L-fluorophenylalanine (p-FPA; HTD: 250 micrograms/ml) and phorbol-12-myristate-13-acetate (TPA; HTD: 50 micrograms/ml). A marginal increase in the frequency of mitotic chromosome malsegregation was obtained with cyclophosphamide in the presence of S9. Thus our test results largely disagree with those previously published by various authors and taken as conclusive by EPA. We interpret the discrepancies to be due to lack of properly controlled testing (e.g., no check for multiple mutational events). Only with a careful test design it is possible to discriminate between chemicals inducing only chromosome loss and no other genetic effects (e.g., acetone, oncodazole), chemicals inducing a variety of genetic damage but no chromosome loss (e.g., EMS, MMS) and chemicals inducing neither chromosome loss nor other genetic events in yeast (e.g., TPA, p-FPA).

Acetone↗

The relationship of insects to the deterioration of stored grain by fungi.

The data presented tests the hypothesis that knowledge of basic biological relationships between insects and fungi in the stored grain ecosystem can open new paths for management of the system. Evidence indicates: (1) some storage insect species are disseminators of storage fungi and some are exterminators; (2) some storage fungi attract storage insects and promote their population increases and other repel and secrete toxins harmful to insects; (3) certain morphophysiologic, biochemical similarities of fungi and the early developmental stages of insects suggest that new protective chemicals, 'insecticidal fungicides', could be designed or specifically sought. A specific example of a naturally occurring compound with dual action, sorbic acid (2,4-hexadienoic acid), is given and its effect on both insects and fungi is discussed. Sorbic acid is the only compound in the U.S. presently labelled by the FDA (Food and Drug Administration) as GRAS (Generally Regarded as Safe) and registered by the EPA (Environmental Protection Agency) for use on grain (maize) in storage.

Animals↗

A computer program linking physiologically based pharmacokinetic model with cancer risk assessment for breast-fed infants.

The risk assessment process predicts the chances of adverse health effects that the toxicant possibly can do to the target organism under expected conditions of exposure. Regulators chose among several mathematical approaches to estimate the risk, but in each case it is necessary to link the dosemetrics of the toxicant with its predicted health effect. In this paper, a computer program is described that allowed us to link a physiologically based pharmacokinetic (PBPK) model for tetrachloroethylene (PCE) in the lactating mother with the estimate of extra cancer risk for breast-fed infants, according to the U.S. Environmental Protection Agency (EPA) methodology. When inhaled by a lactating woman, PCE may partition into breast milk and may be transferred to the breast-fed infant. We have developed and validated experimentally a PBPK model for lactational transfer of PCE in rats, including a quantitative description of a milk compartment and the nursing pup. Subsequently, the model has been scaled to describe human physiology, and was validated with literature data for human cases of PCE exposure. Finally, we linked the dosage predictions of the PBPK model with equations used by EPA to estimate the cancer risk from PCE. The model predictions are in good agreement with both the measured values and those reported in the literature for exposure to PCE. This comparison confirms the usefulness of PBPK modeling in risk assessments.

Air Pollutants↗