The physicochemical basis of QSARs for baseline toxicity.

The physico-chemical properties relevant to the equilibrium partitioning (bioconcentration) of chemicals between organisms and their respired media of water and air are reviewed and illustrated for chemicals that range in hydrophobicity. Relationships are then explored between freely dissolved external concentrations such as LC50s and chemical properties for one important toxicity mechanism, namely baseline toxicity or narcosis. The 'activity hypothesis' proposed by Ferguson in 1939 provides a coherent and compelling explanation for baseline toxicity of chemicals in both water- and air-respiring organisms, as well as a reference point for identifying more specific toxicity pathways. From inhalation studies with fish and rodents, narcosis is shown to occur at a chemical activity exceeding approximately 0.01 and there is no evidence of narcosis at activities less than 0.001. The activity hypothesis provides a framework for directly comparing the toxic potency of chemicals in both air- and water-breathing animals. The activity hypothesis is shown to be consistent with the critical body residue concept, but it has the advantage of avoiding the confounding effect of lipid content of the test organism. It also provides a theoretically sound basis for assessing the baseline toxicity of mixtures. It is suggested that since activity is readily calculated from fugacity, observed or predicted environmental abiotic and biotic fugacities can be used to evaluate the potential for baseline toxicity. Further, models employing fugacity or activity can be used to improve the experimental design of bioassays, thus possibly reducing unnecessary animal testing.

Evaluation of bioaccumulation and photo-induced toxicity of fluoranthene in larval and adult life-stages of Chironomus tentans.

Laboratory sediment tests were conducted to evaluate the bioaccumulation and photo-induced toxicity of fluoranthene in larval and adult life-stages of the midge, Chironomus tentans. In the first of 2 experiments, fourth-instar and adult C. tentans exposed to spiked sediments (204 microg fluoranthene/g dry weight) were collected for determination of fluoranthene tissue concentrations and toxicity after ultraviolet (UV) radiation treatment in the absence of sediment (water-only). Fluoranthene tissue concentrations in larvae collected after a 72-hour exposure period were 7 times greater than concentrations in adults collected on emergence from the same spiked sediments. Fluoranthene-exposed adults were tolerant of UV exposure (100% survival after 7 hours), whereas larvae were sensitive (0% survival after 1 hour). In the second experiment, C. tentans larvae were exposed for 96 hours to 2 sediment treatments (170 and 54 microg fluoranthene/g dry weight), after which fluoranthene tissue concentrations were determined and UV exposures conducted under water-only versus sediment conditions. Exposure to UV radiation, in conjunction with sediment, provided larvae with significant protection from photo-induced toxicity compared with the water-only exposure. Adults that emerged from the 2 sediment treatments were also analyzed for fluoranthene tissue residues and exposed to UV radiation. Fluoranthene tissue residues were higher in adult female than in adult male midges, but exuviae from both sexes contained higher fluoranthene concentrations than whole-body tissue, thus demonstrating that the molting process is a possible detoxification mechanism. Consistent with the greater tissue residue concentrations, female midges demonstrated a significant decrease in survival under UV exposure compared with male midges. These studies indicated that both the burrowing behavior of the larvae and the elimination of fluoranthene in molted exuviae are protective mechanisms against photo-enhanced PAH toxicity in this species.

An assessment of the toxicity of phthalate esters to freshwater benthos. 1. Aqueous exposures.

Tests were performed with the freshwater invertebrates Hyalella azteca, Chironomus tentans, and Lumbriculus variegatus to determine the acute toxicity of six phthalate esters, including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), di-n-hexyl phthalate (DHP), and di-2-ethylhexyl phthalate (DEHP). It was possible to derive 10-d LC50 (lethal concentration for 50% of the population) values only for the four lower molecular weight esters (DMP, DEP, DBP, and BBP), for which toxicity increased with increasing octanol-water partition coefficient (Kow) and decreasing water solubility. The LC50 values for DMP, DEP, DBP, and BBP were 28.1, 4.21, 0.63, and 0.46 mg/L for H. azteca; 68.2, 31.0, 2.64, and > 1.76 mg/L for C. tentans; and 246, 102, 2.48, and 1.23 mg/L for L. variegatus, respectively. No significant survival reductions were observed when the three species were exposed to either DHP or DEHP at concentrations approximating their water solubilities.

An assessment of the toxicity of phthalate esters to freshwater benthos. 2. Sediment exposures.

Seven phthalate esters were evaluated for their 10-d toxicity to the freshwater invertebrates Hyalella azteca and Chironomus tentans in sediment. The esters were diethyl phthalate (DEP), di-n-butyl phthalate (DBP), di-n-hexyl phthalate (DHP), di-(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), diisodecyl phthalate (DIDP), and a commercial mixture of C7, C9, and C11 isophthalate esters (711P). All seven esters were tested in a sediment containing 4.80% total organic carbon (TOC), and DBP alone was tested in two additional sediments with 2.45 and 14.1% TOC. Sediment spiking concentrations for DEP and DBP were based on LC50 (lethal concentration for 50% of the population) values from water-only toxicity tests, sediment organic carbon concentration, and equilibrium partitioning (EqP) theory. The five higher molecular weight phthalate esters (DHP, DEHP, DINP, DIDP, 711P), two of which were tested and found to be nontoxic in water-only tests (i.e., DHP and DEHP), were tested at single concentrations between 2,100 and 3,200 mg/kg dry weight. Preliminary spiking studies were performed to assess phthalate ester stability under test conditions. The five higher molecular weight phthalate esters in sediment had no effect on survival or growth of either C. tentans or H. azteca, consistent with predictions based on water-only tests and EqP theory. The 10-d LC50 values for DBP and H. azteca were >17,400, >29,500, and >71,900 mg/kg dry weight for the low, medium, and high TOC sediments, respectively. These values are more than 30x greater than predicted by EqP theory and may reflect the fact that H. azteca is an epibenthic species and not an obligative burrower. The 10-d LC50 values for DBP and C. tentans were 826, 1,664, and 4.730 mg/kg dry weight for the low, medium, and high TOC sediments, respectively. These values are within a factor of two of the values predicted by EqP theory. Pore-water 10-d LC50 values for DBP (dissolved fraction) and C. tentans in the three sediments were 0.65, 0.89, and 0.66 of the water-only LC50 value of 2.64 mg/L, thereby agreeing with EqP theory predictions to within a factor of 1.5. The LC50 value for DEP and C. tentans was >3,100 mg/kg dry weight, which is approximately 10x that predicted by EqP theory. It is postulated that test chemical loss and reduced organism exposure to pore water may have accounted for the observed discrepancies with EqP calculations for DEP

A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.

Because of their widespread occurrence and substantial biological activity, halogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) comprise one of the more important classes of contaminants in the environment. Some chemicals in this class cause adverse biological effects after binding to an intracellular cytosolic protein called the aryl hydrocarbon receptor (AhR). Toxic responses such as thymic atrophy, weight loss, immunotoxicity, and acute lethality, as well as induction of cytochrome P4501A1, have been correlated with the relative affinity of PCBs, PCDFs, and PCDDs for the AhR. Therefore, an important step in predicting the effects of these chemicals is the estimation of their binding to the receptor. To date, however, the use of quantitative structure activity relationship (QSAR) models to estimate binding affinity across multiple chemical classes has shown only modest success possibly due, in part, to a focus on minimum energy chemical structures as the active molecules. In this study, we evaluated the use of structural conformations other than those of minimum energy for the purpose of developing a model for AhR binding affinity that encompasses more of the halogenated aromatic chemicals known to interact with the receptor. Resultant QSAR models were robust, showing good utility across multiple classes of halogenated aromatic compounds.

Integrated assessment of contaminated sediments in the lower Fox River and Green Bay, Wisconsin.

Samples of sediment and biota were collected from sites in the lower Fox River and southern Green Bay to determine existing or potential impacts of sediment-associated contaminants on different ecosystem components of this Great Lakes area of concern. Evaluation of benthos revealed a relatively depauperate community, particularly at the lower Fox River sites. Sediment pore water and bulk sediments from several lower Fox River sites were toxic to a number of test species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata, Selenastrum capricornutum, and Photobacterium phosphorum. An important component of the observed toxicity appeared to be due to ammonia. Evaluation of three bullhead (Ictalurus) species from the lower Fox River revealed an absence of preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium bioassay indicated relatively little mutagenicity in sediment extracts. Apparent adverse reproductive effects were noted in two species of birds nesting along the lower Fox River and on a confined disposal facility for sediments near the mouth of the river, and there were measurable concentrations of potentially toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in sediments from several of the study sites. Based on toxic equivalency factors and the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota from the lower Fox River/Green Bay system was due to the planar PCBs. The results of these studies are discussed in terms of an integrated assessment focused on providing data for remedial action planning.

Uptake, elimination, and metabolism of three phenols by fathead minnows.

Uptake rates of total 14C in fathead minnows (Pimephales promelas) exposed to sublethal concentrations of radiolabeled test compounds followed the order: phenol > 2,4,5-trichlorophenol > p-nitrophenol. Mean whole body 14C concentration factors were 15,800, 1,850, and 180 for phenol, 2,4,5-trichlorophenol, and p-nitrophenol exposures, respectively. Only minor amounts of tissue 14C was parent compound after 28 days of exposure in fish exposed to phenol and p-nitrophenol, while 78.6% of the 14C was parent compound in 2,4,5-trichlorophenol exposed fish. Tissue 14C in fish exposed to 2,4,5-trichlorophenol was eliminated at a faster rate than in fish exposed to phenol or p-nitrophenol. Observed mean 14C depuration half-lives for lower and higher exposures combined were 387, 150, and 12 hours for phenol, p-nitrophenol, and 2,4,5-trichlorophenol, respectively. Parent compound comprised 1.5, 2.7, and 0.7% of total 14C for phenol, 2,4,5-trichlorophenol, and p-nitrophenol, respectively, after 28 days of depuration. The percentage of acetone-unextractable 14C increased from the end of uptake to the end of depuration for phenol and 2,4,5-trichlorophenol, and decreased slightly for p-nitrophenol. 14C contribution from polar metabolites increased relative to total 14C during the depuration phase for 2,4,5-trichlorophenol and p-nitrophenol.

Insecticides, polychlorinated biphenyls and metals in African lake ecosystems. I. Hartbeespoort Dam, Transvaal and Voëlvlei Dam, Cape Province, Republic of South Africa.

Concentrations and distribution of chlorinated hydrocarbon insecticides, polychlorinated biphenyls (PCB's) and some metals were determined in two South African lakes, Hartbeespoort Dam and Voëlvlei Dam. Water, bottom sediments, aquatic plants, aquatic insects, fish, fish-eating birds and their eggs were collected. Insecticides and PCB's were analyzed by thin layer and gas chromatography and mass-spectrometry. Analysis of metals was accomplished with atomic absorption spectrophotometry. Metals included arsenic, cadmium, copper, mangenese, lead, zinc, and mercury. The insecticide residue most commonly found in both dams were DDE, DDD, DDT, and dieldrin. Hartbeespoort had higher levesl than Voëlvlei of insecticides and PCB's in all types of samples common to both lakes. Concentrations of PCB's in all types of samples common to both lakes. Concentrations of PCB's having six or more chlorines increased with an increase in the trophic level. Concentrations of PCB's in the brains of the African birds were greater than the average total concentration of insecticides while the opposite was true for carcasses. Biological magnification of insecticides and PCB's occurred in both lakes. Hartbeespoort Dam had higher levels than Voëlvlei for all metals examined in bottom sediments and birds, except for copper in bird carcasses. Mercury levels in bird carcasses ranged from 2- to 5-fold greater than in fish while lead concentrations ranged from 2- to 10-fold greater.

Gas-liquid chromatographic determination of alachlor (2-chloro-2', 6'-diethyl-N-(methoxymethyl)-acetanilide) herbicide residues in corn and soybeans.

A method has been developed for the extraction and determination of alachlor (2-chloro-2',6'-diethyl-N- (methoxymethyl)-acetanilide) residues in green corn and soybeans. Residues are extracted with acetonitrile and cleaned up on a Florisil column. The methylene chloride extract is sufficiently clean for electron capture gas-liquid chromatographic analysis and for verification by thin layer chromatography. Average recoveries of spiked samples (0.2 ppm) were 69 and 82% for corn and soybeans, respectively. This procedure could be useful for the detection of the parent compound in these crops soon after field application, but it does not detect metabolites.

Physiological effects of polychlorinated biphenyls or a combination of DDT, DDD, and DDE in penned white pelicans.

The effects of PCBs (polychlorinated biphenyls) or a combination of DDT (1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane), DDD (1,1-dichloro-2,2-bis (p-chlorophenyl) ethane) and DDE (1,1-dichloro-2,2,-bis (p-chlorophenyl ethylene) on organ weights, liver storage of vitamin A and carotene, selected blood chemistry parameters, and serum protein fractions were determined in penned white pelicans (Pelecanus erythrorhynchos) receiving a daily dosage of these compounds. Birds received 100 mg of PCBs or a combination of DDT (20 mg), DDD (15 mg), and DDE (15 mg) injected into the first fish fed each day for ten weeks. A greater percentage of PCB treatment was retained in brain, liver, carcass and feathers than the percentage of DDT + DDD + DDE treatment. Liver weight as percent of body weight decreased (p less than 0.01) in DDT + DDD + DDE-treated birds and increased (p less than 0.01) as a total weight in PCB-treated birds. Spleen weight as percent of body weight was greater (p less than 0.05) in PCB-treated birds. Neither treatment had a significant effect on the weight of the brain, heart, or kidney. Liver vitamin A levels were greater (p less than 0.01) on a mug/g of liver basis in the DDT-treated birds than in controls. Significant lowering of serum potassium and protein values was noted in both the PCB- and the combination of DDT, DDD, DDE-treated birds, while serum calcium values were lowered (p less than 0.01) only in PCB-treated birds. Vaues of serum inorganic phosphorus, uric acid and magnesium were not significantly changed by either treatment. Globulin fractions were unaltered by either treatment, but albumin fractions were lowered (p less than 0.01) in the PCB-treated pelicans.